Follicular lymphoma is the most common form of indolent NHL in the United States. It arises from germinal center B cells and is strongly associated with a translocation involving BCL2, which leads to overexpression of the BCL2 protein and promotes cell survival. Diffuse large B-cell lymphoma is the most common form of aggressive NHL, often presenting as a rapidly enlarging mass. Burkitt lymphoma is very aggressive and occurs in three clinical variants associated with distinct epidemiological factors and EBV infection status. Multiple myeloma is characterized by proliferation of plasma cells in the bone marrow leading to lytic bone lesions and organ dysfunction.

1. Peripheral B cell Neoplasm Neoplasm of Mature B cells

2. FOLLICULAR LYMPHOMA

3. FEATURESFollicular lymphoma is the most common form of indolent NHL in the United StatesMiddle age men and women equally.Arise from germinal center B cells.Strongly associated with translocation involving BCL2

4. hallmarkTranslocation( 14; 18) This translocation is seen in most but not all follicular lymphomasLeads to overexpression of BCL2 protein. BCL2, = is an antagonist of apoptotic cell death and appears to promote the survival of follicular lymphoma cells.

5. Features10% show Peripheral blood involvement sufficient to produce lymphocytosis (usually <20,000/mm3 )85% have Bone marrow involvement Paratrabecularlymphoid aggregates.Splenic white pulp and hepatic portal triads are also frequently involved.

6. Reactive LymphoidFollicular Lymphoma HyperplasiaMajority Small cleaved cellsForm Follicles

7. BCL2 Immunostain7

8. Immunophenotype and GeneticsExpress 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

9. Clinical Features.Painless lymphadenopathy, which is frequently generalized. Uncommon Involvement of extranodalsitesGIT, CNS, TestisOften follows an indolent waxing and waning course.

10. SurvivalOverall median survival is 7 to 9 yearsIs not improved by aggressive therapyThe usual clinical approach is to palliate patients with low-dose chemotherapy or radiation when they become symptomatic.

11. TransformationRetain t(14;18)Somatic Hypermutation promote transformationOccurs 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. DIFFUSE LARGE CELL LYMPHOMA

13. Most common form of NHL60-70% Aggressive lymphoid neoplasmM>F , Median age 60y/oDIFFUSE LARGE B-CELL LYMPHOMA

14. FeaturesRapidly enlarging massOften SymptomaticArise in any siteWaldeyerring, Oropharyngeal LN, TonsilsLiver, spleenLocalized Disease with extranodal involvement Rarely present as leukemia

15. ImmunophenotypeMature B cell Express CD19 & CD20Variably Express Germinal Center MarkersHave surface IgNegative Tdt

16. Molecular Pathogenesis30% Dysregulation of BCL6Repress germinal center B-cell Differentiation  Growth Arrest  Holds cell in Undifferentiated Proliferative stateSilence the expression of p53 Prevent the activation of DNA repair mechanism

17. Liver -DLCL

18. MorphologyDiffuse pattern of growthLarge Neoplastic cells4-5x small lymphocytesDIFFUSE LARGE CELL LYMPHOMA

19. Diffuse Large Cell

20. Therapy60-80% Complete remission with combination Chemotherapy50% remain free from disease for yearsImmunotherapy with Anti-CD20 improves outcome especially elderly

21. Subtype Immunedeficiency-associated large B cell LymphomaT cell immunodeficiency ( HIV )(+) EBV Neoplastic B cell Restoration of immunity Regression of proliferation

22. BURKITTS LYMPHOMA

23. BURKITTS LYMPHOMA3 TYPES1. African ( Endemic )2. Sporadic ( Non-endemic )3. Aggressive lymphoma occuring in HIV patientsHistologically identical

24. Genotype & virologic difference

25. CD10 Usually seenFeaturesCell of origin

26. Germinal center Bcell

27. African  LATENTLY INFECTED w/ EBV

28. All forms associated

29. Translocations c-myc gene on Chromosome 8 with IgH [t(8,14)]

30. CommonlyClinical featuresAdolescent or Young Adult w/ jaw or extranodal abdominal massVery aggressiveRespond well to chemotxOutcome guarded in Older adultsUNCOMMON BM or peripheral blood

31. Clinical features Endemic Often as Abdominal MassIleocecalPeritoneumOften Mandibular massUnusual predilection to abdominal visceraKidneysOvaryAdrenalsSporadic

34. MorphologyStarry sky patternHigh mitotic activity

35. BurkittsLymphomaStarry sky pattern

36. High Mitotic IndexMonotonous Cells

37. Marginal Zone Lymphomas

38. FeaturesLOW grade lesionsEncompass a heterogenous group of B cell tumorsArise in LN, Spleen, Extranodal TissuesTumor cell resemble normal Marginal Zone B cellsInitially recognized at mucosal sites MALTOMA

39. Unusual Pathogenesis1. Often arise – Chronic Inflammatory D/OAutoimmuneSjogrens – Salivary glandHashimotos - ThyroidInfectious Helicobacter pylori- Stomach

40. Unusual Pathogenesis2. Remain localized for prolonged periods – Spread late3. May regress if inciting agent is eradictaed – H. pylori

43. GIT- Maltoma

45. MULTIPLE MYELOMA

46. Multiple bone involvementCan also spread to LN & Extranodal1% in Western countriesHigher incidence Men>WomenOlder PatientsRadiation exposureAfrican decentMULTIPLE MYELOMA

47. PathogenesisIL-6 Proliferation of tumor cells are DEPENDENT on CytokioneActive Disease and Poor PrognosisMIP 1 alpha & RANK LigandMediate Bone DestructionKaryotypingDeletions of 13qIgHMULTIPLE MYELOMA

48. X-rayMultiple lyticlesions Punch out lesionsAxial SkeletonStarts at MedullaryGelatinous , soft tumorMULTIPLE MYELOMA

49. Mutiple Myeloma

50. LaboratoryHigh M proteins  Rouleaux55% IgG Monoclonal AbProliferation of Neoplastic plasma cells30% of bone marrow cellularity (Plasma cell Leukemia )Bence Jones proteins in urineMyeloma kidneySeen in 60-80%ClinicopathologicDxCorrelation of X-ray & Laboratory FindingsMULTIPLE MYELOMA

51. BM aspirate- Myeloma

52. ElectrophoresisIgG k M protein

53. Clinical FeaturesBone pain – axial skeleton (Vertebrae)Hypercalcemia ( 25%)Renal Failure (30-50%)Myeloma kidneyProteinacious tubular castNephrocalcinosis ( metastatic calcification)

54. Clinical FeaturesHematologic findingsNormocytic anemia with rouleauxProlonged bleeding due to defect in platelet aggregationRadiculopathy due to bone compression and vertebral fractureRecurrent infection – Most common cause of death

55. PrognosisVariable but Generally PoorMedian survival is 6 months without treatment

56. SOLITARY MYELOMA

57. Solitary MyelomaLesions either in the Bone or Soft TissueAxial SkeletonLungs, Oropharynx, Nasal SinusesMinority show (+) M proteinProgression to Multiple MyelomaCommon in solitary Osseous myeloma ( 10-20 yrs)Less common in Extraosseous