Part 2 nhl

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Part 2 nhl

  1. 1. PERIPHERAL B CELL NEOPLASM NEOPLASM OF MATURE B CELLS
  2. 2. FOLLICULAR LYMPHOMA
  3. 3. 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
  4. 4. 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.
  5. 5. • 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
  6. 6. Reactive Lymphoid Follicular Lymphoma Hyperplasia Majority Small cleaved cells Form Follicles
  7. 7. BCL2 Immunostain 7
  8. 8. • 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
  9. 9. Clinical Features. • Painless lymphadenopathy, which is frequently generalized. • Uncommon Involvement of extranodal sites – GIT, CNS, Testis • Often follows an indolent waxing and waning course.
  10. 10. 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.
  11. 11. 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.
  12. 12. DIFFUSE LARGE CELL LYMPHOMA
  13. 13. • Most common form of NHL • 60-70% • Aggressive lymphoid neoplasm • M>F , Median age 60y/o DIFFUSE LARGE B-CELL LYMPHOMA
  14. 14. • 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
  15. 15. Immunophenotype • Mature B cell • Express CD19 & CD20 • Variably Express Germinal Center Markers • Have surface Ig • Negative Tdt
  16. 16. 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
  17. 17. Liver -DLCL
  18. 18. • Morphology – Diffuse pattern of growth – Large Neoplastic cells • 4-5x small lymphocytes DIFFUSE LARGE CELL LYMPHOMA
  19. 19. Diffuse Large Cell
  20. 20. Therapy • 60-80% Complete remission with combination Chemotherapy – 50% remain free from disease for years • Immunotherapy with Anti-CD20 improves outcome especially elderly
  21. 21. Subtype • Immunedeficiency-associated large B cell Lymphoma – T cell immunodeficiency ( HIV ) – (+) EBV Neoplastic B cell – Restoration of immunity • Regression of proliferation
  22. 22. BURKITTS LYMPHOMA
  23. 23. BURKITTS LYMPHOMA 3 TYPES 1. African ( Endemic ) 2. Sporadic ( Non-endemic ) 3. Aggressive lymphoma occuring in HIV patients o Histologically identical o Genotype & virologic difference o CD10 Usually seen
  24. 24. Features o Cell of origin o Germinal center Bcell o African  LATENTLY INFECTED w/ EBV o All forms associated o Translocations c-myc gene on Chromosome 8 with IgH [t(8,14)] o Commonly
  25. 25. Clinical 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
  26. 26. Clinical features Endemic • Often Mandibular mass • Unusual predilection to abdominal viscera – Kidneys – Ovary – Adrenals Sporadic • Often as Abdominal Mass – Ileocecal – Peritoneum
  27. 27. Morphology – Starry sky pattern – High mitotic activity
  28. 28. Burkitts Lymphoma Starry sky pattern
  29. 29. High Mitotic Index Monotonous Cells
  30. 30. Marginal Zone Lymphomas
  31. 31. 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
  32. 32. Unusual Pathogenesis • 1. Often arise – Chronic Inflammatory D/O – Autoimmune • Sjogrens – Salivary gland • Hashimotos - Thyroid – Infectious • Helicobacter pylori- Stomach
  33. 33. Unusual Pathogenesis • 2. Remain localized for prolonged periods – Spread late • 3. May regress if inciting agent is eradictaed – H. pylori
  34. 34. Chronic inflammation Reactive Polyclonal Immune reaction Acquisition of mutations & Chromosomal aberrations Monoclonal B cells neoplasm emerges Initially dependent on T –Helper cell for growth Continuous mutation Stage independent of extrinsic stimuli – microbe/antigen
  35. 35. GIT- Maltoma
  36. 36. MULTIPLE MYELOMA
  37. 37. • 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
  38. 38. • 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
  39. 39. • X-ray – Multiple lytic lesions • Punch out lesions • Axial Skeleton • Starts at Medullary – Gelatinous , soft tumor MULTIPLE MYELOMA
  40. 40. Mutiple Myeloma
  41. 41. • 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
  42. 42. BM aspirate- Myeloma
  43. 43. Electrophoresis IgG k M protein
  44. 44. Clinical Features • Bone pain – axial skeleton (Vertebrae) • Hypercalcemia ( 25%) • Renal Failure (30-50%) • Myeloma kidney – Proteinacious tubular cast – Nephrocalcinosis ( metastatic calcification)
  45. 45. 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
  46. 46. Prognosis • Variable but Generally Poor • Median survival is 6 months without treatment
  47. 47. SOLITARY MYELOMA
  48. 48. 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
  49. 49. PERIPHERAL T-CELL and NK-CELL NEOPLASMS NEOPLASM OF MATURE T CELLS AND NK CELLS
  50. 50. EXTRANODAL NK/T- CELL LYMPHOMA
  51. 51. 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
  52. 52. Mycosis fungoides

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