dr. Isbandiyah, SpPD dr. Isbandiyah, SpPD Lymphoma Lymphoma
OverviewOverview
Concepts, classificationConcepts, classification EpidemiologyEpidemiology Clinical presentationClinical presentation DiagnosisDiagnosis StagingStaging Three important types of lymphomaThree important types of lymphoma
Conceptualizing lymphomaConceptualizing lymphoma
neoplasms of lymphoid origin, typically neoplasms of lymphoid origin, typically causing lymphadenopathycausing lymphadenopathy
lymphomas as clonal expansions of cells at lymphomas as clonal expansions of cells at certain developmental stagescertain developmental stages
EpidemiologyEpidemiology
55thth most frequently diagnosed cancer overall most frequently diagnosed cancer overall for both males and femalesfor both males and females
males > femalesmales > females incidenceincidence
– NHL increasing over timeNHL increasing over time– Hodgkin lymphoma stableHodgkin lymphoma stable
Lymphoma classificationLymphoma classification(based on 2001 WHO)(based on 2001 WHO)
B-cell neoplasmsB-cell neoplasms– PrecursorPrecursor B-cell neoplasms (2 types) B-cell neoplasms (2 types)– MatureMature B-cell neoplasms (19) B-cell neoplasms (19)– B-cell proliferations of uncertain malignant potential (2)B-cell proliferations of uncertain malignant potential (2)
T-cell & NK-cell neoplasmsT-cell & NK-cell neoplasms– PrecursorPrecursor T-cell neoplasms (3) T-cell neoplasms (3)– MatureMature T-cell and NK-cell neoplasms (14) T-cell and NK-cell neoplasms (14)– T-cell proliferation of uncertain malignant potential (1)T-cell proliferation of uncertain malignant potential (1)
Hodgkin lymphomaHodgkin lymphoma– Classical Hodgkin lymphomas (4)Classical Hodgkin lymphomas (4)– Nodular lymphocyte predominant Hodgkin lymphoma (1)Nodular lymphocyte predominant Hodgkin lymphoma (1)
Clinical manifestationsClinical manifestations VariableVariable
severity: asymptomatic to extremely illseverity: asymptomatic to extremely ill time course: evolution over weeks, months, or time course: evolution over weeks, months, or
yearsyears
Systemic manifestationsSystemic manifestations fever, night sweats, weight loss, anorexia, pruritisfever, night sweats, weight loss, anorexia, pruritis
Local manifestationsLocal manifestations lymphadenopathy, splenomegaly most commonlymphadenopathy, splenomegaly most common any tissue potentially can be infiltratedany tissue potentially can be infiltrated
Other complications of lymphomaOther complications of lymphoma
bone marrow failure (infiltration)bone marrow failure (infiltration) CNS infiltrationCNS infiltration immune hemolysis or thrombocytopeniaimmune hemolysis or thrombocytopenia compression of structures (eg spinal cord, compression of structures (eg spinal cord,
ureters) by bulky diseaseureters) by bulky disease pleural/pericardial effusions, ascitespleural/pericardial effusions, ascites
Diagnosis requires an adequate Diagnosis requires an adequate biopsybiopsy
Diagnosis should be Diagnosis should be biopsy-provenbiopsy-proven before before treatment is initiatedtreatment is initiated
Need enough tissue to assess cells and Need enough tissue to assess cells and architecturearchitecture– open bx open bx vsvs core needle bx core needle bx vsvs FNA FNA
Stage I Stage II Stage III Stage IV
Staging of lymphomaStaging of lymphoma
A: absence of B symptomsB: fever, night sweats, weight loss
Staging WorkupStaging Workup
CBC, chemistries, urinalysisCBC, chemistries, urinalysis USG or CT scans of chest, abdomen and USG or CT scans of chest, abdomen and
pelvispelvis Bone marrow biopsy and aspirateBone marrow biopsy and aspirate (Lumbar puncture)(Lumbar puncture)
– AIDS lymphomaAIDS lymphoma– T cell lymphoblastic lymphomaT cell lymphoblastic lymphoma– High grade lymphoma with positive marrowHigh grade lymphoma with positive marrow
Three types of lymphoma worth Three types of lymphoma worth knowing aboutknowing about
Follicular lymphomaFollicular lymphoma Diffuse large B-cell lymphomaDiffuse large B-cell lymphoma Hodgkin lymphomaHodgkin lymphoma
Follicular lymphomaFollicular lymphoma
most common type of “indolent” lymphomamost common type of “indolent” lymphoma usually widespread at presentationusually widespread at presentation often asymptomaticoften asymptomatic not curable (some exceptions)not curable (some exceptions) associated with BCL-2 gene rearrangement associated with BCL-2 gene rearrangement
[t(14;18)][t(14;18)] cell of origin: germinal center B-cellcell of origin: germinal center B-cell
Diffuse large B-cell lymphomaDiffuse large B-cell lymphoma
most common type of “aggressive” most common type of “aggressive” lymphomalymphoma
usually symptomaticusually symptomatic extranodal involvement is commonextranodal involvement is common cell of origin: germinal center B-cellcell of origin: germinal center B-cell treatment should be offeredtreatment should be offered curable in ~ 40%curable in ~ 40%
Hodgkin lymphomaHodgkin lymphoma
cell of origin: germinal centre B-cell cell of origin: germinal centre B-cell Reed-Sternberg cells (or RS variants) in the Reed-Sternberg cells (or RS variants) in the
affected tissuesaffected tissues most cells in affected lymph node are most cells in affected lymph node are
polyclonal reactive lymphoid cells, not polyclonal reactive lymphoid cells, not neoplastic cellsneoplastic cells
RS cell and variantsRS cell and variants
popcorn celllacunar cellclassic RS cell
(mixed cellularity) (nodular sclerosis) (lymphocytepredominance)
Hodgkin lymphomaHodgkin lymphomaHistologic subtypesHistologic subtypes
Classical Hodgkin lymphomaClassical Hodgkin lymphoma– nodular sclerosis (most common subtype)nodular sclerosis (most common subtype)– mixed cellularitymixed cellularity– lymphocyte-richlymphocyte-rich– lymphocyte depletedlymphocyte depleted
EpidemiologyEpidemiology
less frequent than non-Hodgkin lymphomaless frequent than non-Hodgkin lymphoma overall M>Foverall M>F peak incidence in 3rd decadepeak incidence in 3rd decade
Clinical manifestations:Clinical manifestations:
lymphadenopathylymphadenopathy contiguous spreadcontiguous spread extranodal sites relatively uncommon except extranodal sites relatively uncommon except
in advanced diseasein advanced disease ““B” symptomsB” symptoms
Treatment by StageTreatment by Stage
Stage Therapy % Cure
IA XRT 95
IIA XRT 85
IB, IIB XRT (Total Nodal) 70
IIIA XRT 70
IIIB, IV Combination Chemo 50
Chemotherapy RegimensChemotherapy Regimens
MOPPMOPP
– MMechlorethamine, echlorethamine, OOncovin, ncovin, PProcarbazine, rocarbazine, PPrednisonerednisone
ABVDABVD
– AAdriamycin, driamycin, BBleomycin, leomycin, VVinblastine, inblastine, DDacarbazineacarbazine
Long term complications of Long term complications of treatmenttreatment
infertilityinfertility– MOPP > ABVD; males > femalesMOPP > ABVD; males > females– premature menopausepremature menopause
secondary malignancysecondary malignancy– skin, AML, lung, MDS, NHL, thyroid, breast...skin, AML, lung, MDS, NHL, thyroid, breast...
cardiac disease cardiac disease after Adriamycin treatment.after Adriamycin treatment.
Types of LymphomaTypes of Lymphoma
Indolent (low grade)Indolent (low grade)– Life expectancy in years, untreatedLife expectancy in years, untreated– 85-90% present in Stage III or IV85-90% present in Stage III or IV– IncurableIncurable
IntermediateIntermediate Aggressive (high grade)Aggressive (high grade)
– Life expectancy in weeks, untreatedLife expectancy in weeks, untreated– Potentially curablePotentially curable
Commonly Used Commonly Used ClassificationsClassifications
WorkingWorking FormulationFormulation
Low GradeLow Grade
Small lymphocyticSmall lymphocytic
Follicular small cleavedFollicular small cleaved
Follicular mixedFollicular mixed
RappaportRappaport
Diffuse well-differentiated Diffuse well-differentiated lymphocytic lymphocytic (DWDL or WDLL)(DWDL or WDLL)
Nodular poorly Nodular poorly differentiated differentiated lymphocytic (NPDL)lymphocytic (NPDL)
Nodular mixed Nodular mixed lymphocytic-histiocytic lymphocytic-histiocytic (NM)(NM)
Commonly Used Commonly Used ClassificationsClassifications
WorkingWorking FormulationFormulation
Intermediate GradeIntermediate Grade
Follicular large cellFollicular large cell
Diffuse small cleaved cellDiffuse small cleaved cell
Diffuse mixedDiffuse mixed
Diffuse large cellDiffuse large cell
RappaportRappaport
Nodular histiocytic (NH)Nodular histiocytic (NH)
Diffuse poorly Diffuse poorly differentiated differentiated lymphocytic (DPDL)lymphocytic (DPDL)
Diffuse mixed Diffuse mixed lymphocytic-lymphocytic-histiocytic (DM)histiocytic (DM)
Diffuse histiocytic (DHL)Diffuse histiocytic (DHL)
Commonly Used Commonly Used ClassificationsClassifications
WorkingWorking FormulationFormulation
High GradeHigh Grade
Large cell immunoblasticLarge cell immunoblastic
Lymphoblastic lymphomaLymphoblastic lymphoma
Small noncleaved cellSmall noncleaved cell
• • Burkitt’sBurkitt’s
• • Non-Burkitt’sNon-Burkitt’s
RappaportRappaport
Diffuse histiocytic Diffuse histiocytic (DHL)(DHL)
Diffuse lymphoblasticDiffuse lymphoblastic
Diffuse Diffuse undifferentiated (DU)undifferentiated (DU)
Etiology of NHLEtiology of NHL
Immune suppressionImmune suppression– congenital (Wiskott-Aldrich)congenital (Wiskott-Aldrich)– organ transplant (cyclosporine)organ transplant (cyclosporine)– AIDSAIDS– increasing ageincreasing age
DNA repair defectsDNA repair defects– ataxia telangiectasiaataxia telangiectasia– xeroderma pigmentosumxeroderma pigmentosum
Etiology of NHLEtiology of NHL
Chronic inflammation and antigenic Chronic inflammation and antigenic stimulationstimulation– Helicobacter pylori Helicobacter pylori inflammation, stomachinflammation, stomach– Chlamydia psittaciChlamydia psittaci inflammation, ocular adnexal inflammation, ocular adnexal
tissuestissues– Sjögren’s syndromeSjögren’s syndrome
Viral causesViral causes– EBV and Burkitt’s lymphomaEBV and Burkitt’s lymphoma– HTLV-I and T cell leukemia-lymphomaHTLV-I and T cell leukemia-lymphoma– HTLV-V and cutaneous T cell lymphomaHTLV-V and cutaneous T cell lymphoma– Hepatitis CHepatitis C
Clinical FeaturesClinical Features
LymphadenopathyLymphadenopathy CytopeniasCytopenias Systemic symptomsSystemic symptoms HepatosplenomegalyHepatosplenomegaly FeverFever Night sweatsNight sweats
Treatment Options:Treatment Options:Indolent lymphomasIndolent lymphomas
WDLL, NPDLWDLL, NPDL 10-15% in Stage I or II10-15% in Stage I or II
– potentially curablepotentially curable– local radiotherapylocal radiotherapy
85-90% Stage III or IV85-90% Stage III or IV– incurableincurable– treatment does not prolong survivaltreatment does not prolong survival
Reasons to Treat in Reasons to Treat in Advanced Indolent LymphomasAdvanced Indolent Lymphomas
Constitutional symptomsConstitutional symptoms Anatomic obstructionAnatomic obstruction Organ dysfunctionOrgan dysfunction Cosmetic considerationsCosmetic considerations Painful lymph nodesPainful lymph nodes CytopeniasCytopenias
Treatment Options inTreatment Options inAdvanced Indolent LymphomasAdvanced Indolent Lymphomas
Observation only.Observation only. Radiotherapy to site of problem.Radiotherapy to site of problem. Systemic chemotherapySystemic chemotherapy
– oral agents: chlorambucil and prednisoneoral agents: chlorambucil and prednisone– IV agents: CHOP, COP, fludarabine, 2-CDA.IV agents: CHOP, COP, fludarabine, 2-CDA.
Antibody against CD20: Rituxan, Bexxar, Antibody against CD20: Rituxan, Bexxar, Zevalin.Zevalin.
Stem cell or bone marrow transplant.Stem cell or bone marrow transplant.