Part 2 Nhl
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Transcript of Part 2 Nhl
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PERIPHERAL B CELL NEOPLASM
NEOPLASM OF MATURE B CELLS
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FOLLICULAR LYMPHOMA FOLLICULAR LYMPHOMA
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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
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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.
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• 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
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Reactive LymphoidFollicular Lymphoma Hyperplasia
Majority Small cleaved cellsForm Follicles
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7
BCL2 Immunostain
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• 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
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Clinical Features.
• Painless lymphadenopathy, which is frequently generalized.
• Uncommon Involvement of extranodal sites–GIT, CNS, Testis
• Often follows an indolent waxing and waning course.
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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.
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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.
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DIFFUSE LARGE CELL LYMPHOMA
DIFFUSE LARGE CELL LYMPHOMA
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• Most common form of NHL• 60-70% • Aggressive lymphoid neoplasm• M>F , Median age 60y/o
DIFFUSE LARGE B-CELL LYMPHOMA
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• 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
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Immunophenotype• Mature B cell • Express CD19 & CD20• Variably Express Germinal Center
Markers• Have surface Ig• Negative Tdt
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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
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Liver -DLCL
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• Morphology– Diffuse pattern of growth– Large Neoplastic cells
• 4-5x small lymphocytes
DIFFUSE LARGE CELL LYMPHOMA
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Diffuse Large Cell
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Therapy• 60-80% Complete remission with
combination Chemotherapy– 50% remain free from disease for years
• Immunotherapy with Anti-CD20 improves outcome especially elderly
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Subtype • Immunedeficiency-associated
large B cell Lymphoma– T cell immunodeficiency ( HIV )– (+) EBV Neoplastic B cell – Restoration of immunity
• Regression of proliferation
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BURKITTS LYMPHOMABURKITTS LYMPHOMA
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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
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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
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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
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Clinical featuresClinical features Endemic
• Often Mandibular mass
• Unusual predilection to abdominal viscera– Kidneys– Ovary– Adrenals
Sporadic• Often as
Abdominal Mass– Ileocecal– Peritoneum
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MorphologyMorphology– Starry sky pattern– High mitotic activity
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Burkitts LymphomaStarry sky pattern
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High Mitotic IndexMonotonous Cells
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Marginal Zone Lymphomas
Marginal Zone Lymphomas
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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
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Unusual Pathogenesis• 1. Often arise – Chronic
Inflammatory D/O– Autoimmune
• Sjogrens – Salivary gland• Hashimotos - Thyroid
– Infectious • Helicobacter pylori- Stomach
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Unusual Pathogenesis• 2. Remain localized for
prolonged periods – Spread late
• 3. May regress if inciting agent is eradictaed – H. pylori
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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
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GIT- Maltoma
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MULTIPLE MYELOMAMULTIPLE MYELOMA
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• 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
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• 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
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• X-ray– Multiple lytic lesions
• Punch out lesions• Axial Skeleton• Starts at Medullary
– Gelatinous , soft tumor
MULTIPLE MYELOMA
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Mutiple Myeloma
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• 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
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BM aspirate- Myeloma
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Electrophoresis
IgG k M protein
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Clinical Features• Bone pain – axial skeleton
(Vertebrae)• Hypercalcemia ( 25%)• Renal Failure (30-50%)• Myeloma kidney
– Proteinacious tubular cast– Nephrocalcinosis ( metastatic
calcification)
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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
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Prognosis• Variable but Generally Poor• Median survival is 6 months without
treatment
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SOLITARY MYELOMASOLITARY MYELOMA
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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
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PERIPHERAL T-CELL and NK-CELL NEOPLASMS
PERIPHERAL T-CELL and NK-CELL NEOPLASMS
NEOPLASM OF MATURE T CELLS AND NK CELLS
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EXTRANODAL NK/T-CELL LYMPHOMA
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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
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Mycosis fungoides