Lymphoma Dr Mohammed Alqahtani CSLT(CG), CLSp(CG), RT,MBA, Ph.D Genomic Medicine Unit Founder & Director Center of Excellence in Genomic Medicine Research.
Post on 21-Dec-2015
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Lymphoma
Dr Mohammed AlqahtaniCSLT(CG) CLSp(CG) RTMBA PhD
Genomic Medicine Unit Founder amp Director
Center of Excellence in Genomic Medicine Research Founder amp Director
Overview
bull Concepts classification biology
bull Epidemiology
bull Clinical presentation
bull Diagnosis
bull Staging
bull Three important types of lymphoma
How Cancer Develops
bull Normal cells are programmed to multiply die when theyrsquore old
bull Signals to multiply and die are controlled by specific genes
bull Mutations can occur in these genesbull If enough mutations occur in genes
controlling growth or cell death a cell begins to multiply uncontrollably
bull The cell has then become cancerous or ldquomalignantrdquo
Features common to cancer cells
bull Growth in the absence of ldquogordquo signals
bull Growth despite ldquostoprdquo signals
bull Locally invasive growth and metastases to distant sites
Bone Marrow
bull Present in the soft inner part of some bones such as the skull shoulder blade ribs pelvis and backbones (Occupies central cavity of bone)
bull The bone marrow is made up of blood-forming stem cells lymphoid tissue fat cells and supporting tissues that aid the growth of blood forming cells
Bone Marrow
bull Spongy tissue where development of all types of blood cells takes place
bull All bones have active marrow at birth
bull Adulthood - vertebrae hip shoulders ribs breast and skull contain marrow
Bone Marrow AspirationBiopsy
Hematopoietic Malignancies
1048708 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series
1048708 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Overview
bull Concepts classification biology
bull Epidemiology
bull Clinical presentation
bull Diagnosis
bull Staging
bull Three important types of lymphoma
How Cancer Develops
bull Normal cells are programmed to multiply die when theyrsquore old
bull Signals to multiply and die are controlled by specific genes
bull Mutations can occur in these genesbull If enough mutations occur in genes
controlling growth or cell death a cell begins to multiply uncontrollably
bull The cell has then become cancerous or ldquomalignantrdquo
Features common to cancer cells
bull Growth in the absence of ldquogordquo signals
bull Growth despite ldquostoprdquo signals
bull Locally invasive growth and metastases to distant sites
Bone Marrow
bull Present in the soft inner part of some bones such as the skull shoulder blade ribs pelvis and backbones (Occupies central cavity of bone)
bull The bone marrow is made up of blood-forming stem cells lymphoid tissue fat cells and supporting tissues that aid the growth of blood forming cells
Bone Marrow
bull Spongy tissue where development of all types of blood cells takes place
bull All bones have active marrow at birth
bull Adulthood - vertebrae hip shoulders ribs breast and skull contain marrow
Bone Marrow AspirationBiopsy
Hematopoietic Malignancies
1048708 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series
1048708 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
How Cancer Develops
bull Normal cells are programmed to multiply die when theyrsquore old
bull Signals to multiply and die are controlled by specific genes
bull Mutations can occur in these genesbull If enough mutations occur in genes
controlling growth or cell death a cell begins to multiply uncontrollably
bull The cell has then become cancerous or ldquomalignantrdquo
Features common to cancer cells
bull Growth in the absence of ldquogordquo signals
bull Growth despite ldquostoprdquo signals
bull Locally invasive growth and metastases to distant sites
Bone Marrow
bull Present in the soft inner part of some bones such as the skull shoulder blade ribs pelvis and backbones (Occupies central cavity of bone)
bull The bone marrow is made up of blood-forming stem cells lymphoid tissue fat cells and supporting tissues that aid the growth of blood forming cells
Bone Marrow
bull Spongy tissue where development of all types of blood cells takes place
bull All bones have active marrow at birth
bull Adulthood - vertebrae hip shoulders ribs breast and skull contain marrow
Bone Marrow AspirationBiopsy
Hematopoietic Malignancies
1048708 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series
1048708 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Features common to cancer cells
bull Growth in the absence of ldquogordquo signals
bull Growth despite ldquostoprdquo signals
bull Locally invasive growth and metastases to distant sites
Bone Marrow
bull Present in the soft inner part of some bones such as the skull shoulder blade ribs pelvis and backbones (Occupies central cavity of bone)
bull The bone marrow is made up of blood-forming stem cells lymphoid tissue fat cells and supporting tissues that aid the growth of blood forming cells
Bone Marrow
bull Spongy tissue where development of all types of blood cells takes place
bull All bones have active marrow at birth
bull Adulthood - vertebrae hip shoulders ribs breast and skull contain marrow
Bone Marrow AspirationBiopsy
Hematopoietic Malignancies
1048708 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series
1048708 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Bone Marrow
bull Present in the soft inner part of some bones such as the skull shoulder blade ribs pelvis and backbones (Occupies central cavity of bone)
bull The bone marrow is made up of blood-forming stem cells lymphoid tissue fat cells and supporting tissues that aid the growth of blood forming cells
Bone Marrow
bull Spongy tissue where development of all types of blood cells takes place
bull All bones have active marrow at birth
bull Adulthood - vertebrae hip shoulders ribs breast and skull contain marrow
Bone Marrow AspirationBiopsy
Hematopoietic Malignancies
1048708 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series
1048708 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Bone Marrow
bull Spongy tissue where development of all types of blood cells takes place
bull All bones have active marrow at birth
bull Adulthood - vertebrae hip shoulders ribs breast and skull contain marrow
Bone Marrow AspirationBiopsy
Hematopoietic Malignancies
1048708 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series
1048708 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Bone Marrow AspirationBiopsy
Hematopoietic Malignancies
1048708 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series
1048708 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Hematopoietic Malignancies
1048708 Lymphoma is a general term for
hematopoietic solid malignancies of
the lymphoid series
1048708 Leukemia is a general term for liquid
malignancies of either the lymphoid
or the myeloid series
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Conceptualizing lymphoma
bull neoplasms of lymphoid origin typically causing lymphadenopathy
bull leukemia vs lymphoma
bull lymphomas as clonal expansions of cells at certain developmental stages
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
What is Lymphoma
bull Lymphomas are cancers that begin by the ldquomalignant transformationrdquo of a lymphocyte in the lymphatic system
bull Many lymphomas are known to be due to specific genetic mutations
bull Follicular lymphoma due to overexpression of BCL-2 (gene that blocks programmed cell death)
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
What is the Lymphatic System
bull Made up of organs such as the tonsils spleen liver bone marrow and a network of lymphatic vessels that connect glands called lymph nodes
bull Lymph nodes located throughout the bodybull Lymph nodes filter foreign particles out of the
lymphatic fluid bull Contain B and T lymphocytes
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Lymphatic System
bull Lymph nodes act as a filter to remove bacteria viruses and foreign particles
bull Most people will have had ldquoswollen glandsrdquo at some time as a response to infection
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Blood Cell and Lymphocyte Development
STEM CELLS
Multipotential myeloid cells
Multipotential lymphocytic cells
Differentiate amp mature into 6 Types of blood cells
red cells basophilsneutrophils monocyteseosinophils platelets
Differentiate amp mature into 3Types of lymphocytes
T lymphocytesB lymphocytesNatural Killer Cells
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Lymphocytesbull Most lymphocytes are in lymph nodes
spleen bone marrow and lymphatic vesselsbull 20 of white blood cells in blood are
lymphocytesbull T cells B cells natural killer cellsbull B cells produce antibodies that help fight
infectious agentsbull T cells help B cells produce antibodies and
they fight viruses
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
T-Cells and B-Cells
1048708 Immature lymphocytes that travel to thethymus differentiate into T-Cells
ndash ldquoTrdquo is for thymus
1048708 Immature lymphocytes that travel to thespleen or lymph nodes differentiate into Bcells
ndash B stands for the bursa of Fabricius which is
an organ unique to birds where B cellsmature
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
ALLALL MM MM CLLCLL LymphomasLymphomas
Hematopoieticstem cell
Neutrophils
Eosinophils
Basophils
Monocytes
Platelets
Red cells
Myeloidprogenitor
Myeloproliferative disordersMyeloproliferative disordersAMLAML
Lymphoidprogenitor T-lymphocytes
Plasmacells
B-lymphocytes
nanaiumliumlveve
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
B-cell development
stemcell
lymphoidprogenitor
progenitor-B
pre-B
immatureB-cell
memoryB-cell
plasma cellplasma cell
DLBCLFL HL
ALL
CLL
MM
germinalgerminalcentercenterB-cellB-cell
maturenaiveB-cell
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Clinically useful classification
Diseases that have distinctbull clinical featuresbull natural historybull prognosisbull treatment
Biologically rational classification
Diseases that have distinctbull morphologybull immunophenotypebull genetic featuresbull clinical features
Classification
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Classification
bull Usually classified by how the cells look under a microscope and how quickly they grow and spreadndash Aggressive lymphomas (high-grade
lymphomas)
ndash Indolent Lymphomas (low-grade lymphomas)
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Lymphoma classification(2001 WHO)
bull B-cell neoplasmsndash precursorndash mature
bull T-cell amp NK-cell neoplasmsndash precursorndash mature
bull Hodgkin lymphoma
Non-HodgkinLymphomas
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Three common lymphomas
bull Follicular lymphoma
bull Diffuse large B-cell lymphoma
bull Hodgkin lymphoma
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Relative frequencies of different lymphomas
Hodgkinlymphoma
NHL
Diffuse large B-cell
Follicular
Other NHL
Non-Hodgkin Lymphomas
~85 of NHL are B-lineage
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Follicular lymphoma
bull most common type of ldquoindolentrdquo lymphoma
bull usually widespread at presentationbull often asymptomaticbull not curable (some exceptions)bull associated with BCL-2 gene
rearrangement [t(1418)]bull cell of origin germinal center B-cell
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
bull defer treatment if asymptomatic (ldquowatch-and-waitrdquo)
bull several chemotherapy options if symptomatic
bull median survival years
bull despite ldquoindolentrdquo label morbidity and mortality can be considerable
bull transformation to aggressive lymphoma can occur
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Diffuse large B-cell lymphoma
bull most common type of ldquoaggressiverdquo lymphoma
bull usually symptomatic
bull extranodal involvement is common
bull cell of origin germinal center B-cell
bull treatment should be offered
bull curable in ~ 40
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
B-Cell Lymphoma (80)
bull B-Cells help make antibodies which are proteins that attach to and help destroy antigens
bull Lymphomas are caused when a mutation arises during the B-cell life cycle
bull Various different lymphomas can occur during several different stages of the cyclendash Follicular lymphoma which is a type of B-cell
lymphoma is caused by a gene translocation which results in an over expressed gene called BCL-2 which blocks apoptosis
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
T-Cell Lymphoma (15)
bull The T-cells are born from stem cells similar to that of B-cells but mature in the thymus
bull They help the immune system work in a coordinated fashionndash These types of lymphomas are categorized
by how the cell is affectedbull Anaplastic Large cell Lymphoma t-cell
lymphoma caused by a gene translocation in chromosome 5
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Mechanisms of lymphomagenesis
bull Genetic alterations
bull Infection
bull Antigen stimulation
bull Immunosuppression
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Epidemiology of lymphomas
bull males gt femalesbull incidence
ndash NHL increasingndash Hodgkin lymphoma stable
bull in NHL 3rd most frequently diagnosed cancer in males and 4th in females
bull in HL 5th most frequently diagnosed cancer in males and 10th in females
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Age distribution of new NHL
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
Inci
denc
e10
000
0an
num
0
20
40
60
80
100
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Risk factors for NHL
bull immunosuppression or immunodeficiency
bull connective tissue disease
bull family history of lymphoma
bull infectious agents
bull ionizing radiation
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Clinical manifestationsbull Variable
bull severity asymptomatic to extremely illbull time course evolution over weeks months or
years
bull Systemic manifestationsbull fever night sweats weight loss anorexia pruritis
bull Local manifestationsbull lymphadenopathy splenomegaly most commonbull any tissue potentially can be infiltrated
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Other complications of lymphoma
bull bone marrow failure (infiltration)
bull CNS infiltration
bull immune hemolysis or thrombocytopenia
bull compression of structures (eg spinal cord ureters)
bull pleuralpericardial effusions ascites
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Non-Hodgkinrsquos LymphomaStaging
bull Stage is the term used to describe the extent of tumor that has spread through the body ( I and II are localized where as III and IV are advanced
bull Each stage is then divided into categories A B and Endash A No systemic symptomsndash B Systemic Symptoms such as fever night
sweats and weight lossndash E Spreading of disease from lymph node to
another organ
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Stage I Stage II Stage III Stage IV
Staging of lymphoma
A absence of B symptomsB fever night sweats weight loss
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Staging
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Symptoms
bull Painful Swelling of lymph nodes located in the neck underarm and groin
bull Unexplained Fever
bull Night Sweats
bull Constant Fatigue
bull Unexplained Weight loss
bull Itchy Skin
Cancer Sourcebook
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Causes and Risk Factors
bull The Exact causes are still unknownndash Higher risk for individuals who
bull Exposed to chemicals such as pesticides or solvents
bull Infected w Epstein-Barr Virusbull Family history of NHL (although no hereditary
pattern has been established)bull Infected w Human Immunodeficiency Virus
(HIV)
Lymphomaorg
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Diagnosis Staging Studies
bull Bone marrow aspiration and biopsy
bull Radionuclide scans
bull GI x-rays
bull Spinal fluid analysis
bull CT scans
bull Magnetic Resonance Imaging (MRI)
bull Biopsy
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Diagnosis requires an adequate biopsy
bull Diagnosis should be biopsy-proven before treatment is initiated
bull Need enough tissue to assess cells and architecturendash open bx vs core needle bx vs FNA
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Treatment
bull Non-Hodgkinrsquos Lymphoma is usually treated by a team of physicians including hematologists medical oncologists and a radiation oncologist
bull In some cases such as for Indolent lymphomas the Doctor may wait to start treatment until the patient starts showing symptoms known as ldquowatchful waitingrdquo
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Treatment Options
bull Chemotherapybull Radiationbull Bone Marrow Transplantationbull Surgerybull Bortezomib (Velcade)bull Immunotherapy
bull Using the bodies own immune system combined with material made in a lab
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Survival Rates
bull Survival Rates vary widely by cell type and staging
ndash 1 Year Survival Rate 77
ndash 5 Year Survival Rate 56
ndash 10 Year Survival Rate 42Cancerorg
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Hodgkin lymphoma
Thomas Hodgkin(1798-1866)
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Classical Hodgkin Lymphoma
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Hodgkin lymphoma
bull cell of origin germinal centre B-cell
bull Reed-Sternberg cells (or RS variants) in the affected tissues
bull most cells in affected lymph node are polyclonal reactive lymphoid cells not neoplastic cells
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Reed-Sternberg cell
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
RS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
A possible model of pathogenesis
germinalcentreB cell
transformingevent(s)
loss of apoptosis
RS cellinflammatory
response
EBV
cytokines
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Hodgkin lymphomaHistologic subtypes
bull Classical Hodgkin lymphomandash nodular sclerosis (most common subtype)ndash mixed cellularityndash lymphocyte-richndash lymphocyte depleted
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Epidemiology
bull less frequent than non-Hodgkin lymphoma
bull overall MgtF
bull peak incidence in 3rd decade
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Age distribution of new Hodgkin lymphoma cases
Age (years)
0-1
1-4
5-9
10-1
415
-19
20-2
425
-29
30-3
435
-39
40-4
445
-49
50-5
455
-59
60-6
465
-69
70-7
475
-79
80-8
485
+
inci
denc
e10
000
0an
num
0
1
2
3
4
5
6
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Associated (etiological) factors
bull EBV infection
bull smaller family size
bull higher socio-economic status
bull caucasian gt non-caucasian
bull possible genetic predisposition
bull other HIV occupation herbicides
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Clinical manifestations
bull lymphadenopathy
bull contiguous spread
bull extranodal sites relatively uncommon except in advanced disease
bull ldquoBrdquo symptoms
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Treatment and Prognosis
Stage Treatment Failure-free
survival
Overall 5 year
survival
III ABVD x 4 amp radiation
70-80 80-90
IIIIV ABVD x 6 60-70 70-80
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Long term complications of
treatmentbull infertility
ndash MOPP gt ABVD males gt femalesndash sperm banking should be discussedndash premature menopause
bull secondary malignancyndash skin AML lung MDS NHL thyroid
breast
bull cardiac disease
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
A practical way to think of lymphoma
Category Survival of untreated patients
Curability To treat or not to treat
Non-Hodgkin lymphoma
Indolent Years Generally not curable
Generally defer Rx if asymptomatic
Aggressive Months Curable in some
Treat
Very aggressive
Weeks Curable in some
Treat
Hodgkin lymphoma
All types Variable ndash months to years
Curable in most
Treat
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Lab Diagnostic Studies
bull Lymph node biopsy
bull Bone marrow aspiration and biopsy
bull Immunohistochemistry
bull Flow cytometry
bull Molecular Genetic studies
bull FISH
bull Cytogenetics
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Cytogenetic Lab
bull t(1418) common (about 30)ndash Bcl-2ndash Follicular growth pattern
bull t(814) common in Burkittrsquos c-myc
bull Multiple anomalies common
bull Correlation between cytogenetic change and outcome is variable
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
In the next slide two examples of a lymphoma hybridised with a split-apart probe are shown
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sections
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Truncated nucleus
Truncated nuclei
Myc split-apart
probe
Probe 1+2
Large cell lymphoma Case 1
Large cell lymphoma Case 1
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
FISH analysis of paraffin embedded tissue Interpretation of results
Case 1 Case 2
Signals (even in truncated cells) are fused excluding a translocation
Some nuclei contain split signals indicating a translocation
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
FISH analysis of paraffin embedded tissue sectionsFISH analysis of paraffin
embedded tissue sectionsThere are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis There are now plentiful examples of how the FISH procedure is needed in routine lymphoma diagnosis
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
MALT lymphomas with the t(1118)(q32q21) translocation For many laboratories FISH analysis is more convenient than a PCR procedure for detecting such cases
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
ldquoBurkitt-likerdquo lymphomas Cases suggestive of Burkittrsquos lymphoma but with atypical features should be analysed by the FISH technique for evidence of MYC translocation
What future applications of the FISH technique are likely to emerge in the future What future applications of the FISH technique are likely to emerge in the future
One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)One area lies in the detection of chromosomal amplifications and deletions of clinical significance (CGH)
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Bea et al (2005) Blood 1063183-3190 Tagawa et al Blood (2005)1061770-1777
For example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphomaFor example specific patterns of chromosomal gains or losses have been noted in diffuse large B cell lymphoma
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Molecular Cytogenetic Lab
Recurrent molecular abnormalities in lymphoma
bull t(1418) Bcl2 - JH in follicular lymphomabull t(1114) Bcl1 - JH in Mantle Zone lymphomabull t(314) Bcl6 - JH in Diffuse Large Cell
lymphomabull t(814) cMyc - JH in Burkitt lymphomabull t(25) ALK-NPM in Anaplastic Large Cell
Lymphoma
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
Histology LabRS cell and variants
popcorn celllacunar cellclassic RS cell(mixed cellularity) (nodular sclerosis) (lymphocyte
predominance)
- Lymphoma
- Overview
- How Cancer Develops
- Features common to cancer cells
- Bone Marrow
- Bone Marrow
- Bone Marrow AspirationBiopsy
- Hematopoietic Malignancies
- Conceptualizing lymphoma
- What is Lymphoma
- What is the Lymphatic System
- Lymphatic System
- Slide 13
- Slide 14
- Blood Cell and Lymphocyte Development
- Lymphocytes
- T-Cells and B-Cells
- Slide 18
- B-cell development
- Classification
- Slide 21
- Lymphoma classification (2001 WHO)
- Three common lymphomas
- Relative frequencies of different lymphomas
- Follicular lymphoma
- Slide 26
- Diffuse large B-cell lymphoma
- B-Cell Lymphoma (80)
- T-Cell Lymphoma (15)
- Mechanisms of lymphomagenesis
- Epidemiology of lymphomas
- Slide 32
- Slide 33
- Slide 34
- Slide 35
- Slide 36
- Age distribution of new NHL
- Risk factors for NHL
- Clinical manifestations
- Other complications of lymphoma
- Non-Hodgkinrsquos Lymphoma Staging
- Staging of lymphoma
- Staging
- Symptoms
- Causes and Risk Factors
- Diagnosis Staging Studies
- Diagnosis requires an adequate biopsy
- Treatment
- Treatment Options
- Survival Rates
- Hodgkin lymphoma
- Slide 52
- Slide 53
- Reed-Sternberg cell
- RS cell and variants
- A possible model of pathogenesis
- Hodgkin lymphoma Histologic subtypes
- Epidemiology
- Age distribution of new Hodgkin lymphoma cases
- Associated (etiological) factors
- Slide 61
- Treatment and Prognosis
- Long term complications of treatment
- A practical way to think of lymphoma
- Lab Diagnostic Studies
- Cytogenetic Lab
- FISH analysis of paraffin embedded tissue sections
- Slide 68
- Slide 69
- Slide 70
- Slide 71
- Slide 72
- Slide 73
- Slide 74
- Slide 75
- Slide 76
- Molecular Cytogenetic Lab Recurrent molecular abnormalities in lymphoma
- Histology Lab RS cell and variants
top related