Transcript
PERIPHERAL B CELL NEOPLASM
NEOPLASM OF MATURE B CELLS
FOLLICULAR LYMPHOMA FOLLICULAR LYMPHOMA
FEATURES• Follicular lymphoma is the most
common form of indolent NHL in the United States
• Middle age men and women equally.
• Arise from germinal center B cells.• Strongly associated with
translocation involving BCL2
HALLMARK• Translocation( 14; 18)
–This translocation is seen in most but not all follicular lymphomas
–Leads to overexpression of BCL2 protein.
– BCL2, = is an antagonist of apoptotic cell death and appears to promote the survival of follicular lymphoma cells.
• 10% show Peripheral blood involvement sufficient to produce lymphocytosis (usually <20,000/mm3 )
• 85% have Bone marrow involvement – Paratrabecular lymphoid aggregates.
• Splenic white pulp and hepatic portal triads are also frequently involved.
Features
Reactive LymphoidFollicular Lymphoma Hyperplasia
Majority Small cleaved cellsForm Follicles
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BCL2 Immunostain
• Express CD19, CD20, CD10 – Like Normal follicular center B cells,
• CD5 is NOT Expressed – In contrast to CLL and SLL and mantle
cell lymphoma, CD5 is expressed. • OverExpression of BCL2 protein - >
90%– Versus Normal Follicular center B cells,
which are BCL2 negative
Immunophenotype and Genetics
Clinical Features.
• Painless lymphadenopathy, which is frequently generalized.
• Uncommon Involvement of extranodal sites–GIT, CNS, Testis
• Often follows an indolent waxing and waning course.
Survival
• Overall median survival is 7 to 9 years– Is not improved by aggressive
therapy–The usual clinical approach is to
palliate patients with low-dose chemotherapy or radiation when they become symptomatic.
Transformation• Retain t(14;18)• Somatic Hypermutation promote
transformation• Occurs in 30 to 50% of follicular
lymphomas, – Most commonly to diffuse large B-cell
lymphoma. • Median survival is less than 1 year
after transformation.
DIFFUSE LARGE CELL LYMPHOMA
DIFFUSE LARGE CELL LYMPHOMA
• Most common form of NHL• 60-70% • Aggressive lymphoid neoplasm• M>F , Median age 60y/o
DIFFUSE LARGE B-CELL LYMPHOMA
• Rapidly enlarging mass• Often Symptomatic• Arise in any site
– Waldeyer ring, Oropharyngeal LN, Tonsils
– Liver, spleen• Localized Disease with
extranodal involvement • Rarely present as leukemia
Features
Immunophenotype• Mature B cell • Express CD19 & CD20• Variably Express Germinal Center
Markers• Have surface Ig• Negative Tdt
Molecular Pathogenesis• 30% Dysregulation of BCL6
– Repress germinal center B-cell Differentiation Growth Arrest Holds cell in Undifferentiated Proliferative state
– Silence the expression of p53 • Prevent the activation of DNA repair
mechanism
Liver -DLCL
• Morphology– Diffuse pattern of growth– Large Neoplastic cells
• 4-5x small lymphocytes
DIFFUSE LARGE CELL LYMPHOMA
Diffuse Large Cell
Therapy• 60-80% Complete remission with
combination Chemotherapy– 50% remain free from disease for years
• Immunotherapy with Anti-CD20 improves outcome especially elderly
Subtype • Immunedeficiency-associated
large B cell Lymphoma– T cell immunodeficiency ( HIV )– (+) EBV Neoplastic B cell – Restoration of immunity
• Regression of proliferation
BURKITTS LYMPHOMABURKITTS LYMPHOMA
BURKITTS LYMPHOMABURKITTS LYMPHOMA3 TYPES1. African ( Endemic )2. Sporadic ( Non-endemic )3. Aggressive lymphoma
occuring in HIV patientso Histologically identicalo Genotype & virologic difference
o CD10 Usually seen
FeaturesFeatures
o Cell of originoGerminal center Bcell
o African LATENTLY INFECTED w/ EBV
o All forms associatedoTranslocations c-myc gene on
Chromosome 8 with IgH [t(8,14)]oCommonly
Clinical featuresClinical features• Adolescent or Young Adult w/ jaw or
extranodal abdominal mass• Very aggressive• Respond well to chemotx• Outcome guarded in Older adults• UNCOMMON BM or peripheral blood
Clinical featuresClinical features Endemic
• Often Mandibular mass
• Unusual predilection to abdominal viscera– Kidneys– Ovary– Adrenals
Sporadic• Often as
Abdominal Mass– Ileocecal– Peritoneum
MorphologyMorphology– Starry sky pattern– High mitotic activity
Burkitts LymphomaStarry sky pattern
High Mitotic IndexMonotonous Cells
Marginal Zone Lymphomas
Marginal Zone Lymphomas
Features• LOW grade lesions• Encompass a heterogenous group of
B cell tumors• Arise in LN, Spleen, Extranodal Tissues• Tumor cell resemble normal Marginal
Zone B cells• Initially recognized at mucosal sites
– MALTOMA
Unusual Pathogenesis• 1. Often arise – Chronic
Inflammatory D/O– Autoimmune
• Sjogrens – Salivary gland• Hashimotos - Thyroid
– Infectious • Helicobacter pylori- Stomach
Unusual Pathogenesis• 2. Remain localized for
prolonged periods – Spread late
• 3. May regress if inciting agent is eradictaed – H. pylori
Chronic inflammati
on
Reactive Polyclonal Immune reaction Acquisition
of mutations
& Chromosom
al aberrations
Monoclonal B cells
neoplasm emerges
Initially dependen
t on T –Helper cell for growth
Continuous mutation
Stage independ
ent of extrinsic stimuli – microbe/antigen
GIT- Maltoma
MULTIPLE MYELOMAMULTIPLE MYELOMA
• Multiple bone involvement• Can also spread to LN & Extranodal• 1% in Western countries• Higher incidence
• Men>Women• Older Patients• Radiation exposure• African decent
MULTIPLE MYELOMA
• Pathogenesis– IL-6
• Proliferation of tumor cells are DEPENDENT on Cytokione
• Active Disease and Poor Prognosis– MIP 1 alpha & RANK Ligand
• Mediate Bone Destruction• Karyotyping
– Deletions of 13q– IgH
MULTIPLE MYELOMA
• X-ray– Multiple lytic lesions
• Punch out lesions• Axial Skeleton• Starts at Medullary
– Gelatinous , soft tumor
MULTIPLE MYELOMA
Mutiple Myeloma
• Laboratory– High M proteins Rouleaux
• 55% IgG Monoclonal Ab
– Proliferation of Neoplastic plasma cells• 30% of bone marrow cellularity
(Plasma cell Leukemia )– Bence Jones proteins in urine
• Myeloma kidney• Seen in 60-80%
• Clinicopathologic Dx– Correlation of X-ray & Laboratory Findings
MULTIPLE MYELOMA
BM aspirate- Myeloma
Electrophoresis
IgG k M protein
Clinical Features• Bone pain – axial skeleton
(Vertebrae)• Hypercalcemia ( 25%)• Renal Failure (30-50%)• Myeloma kidney
– Proteinacious tubular cast– Nephrocalcinosis ( metastatic
calcification)
Clinical Features• Hematologic findings
– Normocytic anemia with rouleaux – Prolonged bleeding due to defect in
platelet aggregation• Radiculopathy due to bone
compression and vertebral fracture• Recurrent infection – Most common
cause of death
Prognosis• Variable but Generally Poor• Median survival is 6 months without
treatment
SOLITARY MYELOMASOLITARY MYELOMA
Solitary Myeloma• Lesions either in the Bone or Soft
Tissue– Axial Skeleton– Lungs, Oropharynx, Nasal Sinuses
• Minority show (+) M protein• Progression to Multiple Myeloma
– Common in solitary Osseous myeloma ( 10-20 yrs)
– Less common in Extraosseous
PERIPHERAL T-CELL and NK-CELL NEOPLASMS
PERIPHERAL T-CELL and NK-CELL NEOPLASMS
NEOPLASM OF MATURE T CELLS AND NK CELLS
EXTRANODAL NK/T-CELL LYMPHOMA
EXTRANODAL NK/T-CELL LYMPHOMA
• PREVIOUSLY MIDLINE GRANULOMA• 3% OF NHL IN ASIA• DESTRUCTIVE MIDLINE MASS
INVADE SMALL VESSELS EXTENSIVE ISCHEMIC NECROSIS
• NEOPLASTIC ELEMENTS– MIXTURE OF SMALL & LARGE LYMPHOID
CELLS
Mycosis fungoides
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