1. Lymphoma

2. ALLMMCLLLymphomas Hematopoietic stem cell Neutrophils Eosinophils Basophils Monocytes Platelets Red cells Myeloid progenitor Myeloproliferative disorders AML Lymphoid progenitor T-lymphocytes Plasma cells B-lymphocytes naïve

3. B-cell development stem cell lymphoid progenitor progenitor-B pre-B immature B-cell memory B-cell plasma cell DLBCL, FL, HL ALL CLL MM germinalcenterB-cell mature naive B-cell

4. Lymphoma classification (2001 WHO) B-cell neoplasms –precursor –mature T-cell & NK-cell neoplasms –precursor –mature Hodgkin lymphoma Non- Hodgkin Lymphomas

5. Mechanisms of lymphomagenesis Genetic alterations Infection Antigen stimulation Immunosuppression

6. Epidemiology of lymphomas 5 th most frequently diagnosed cancer in both sexes males > females incidence –NHL increasing –Hodgkin lymphoma stable

7. Risk factors for NHL immunosuppression or immunodeficiency connective tissue disease family history of lymphoma infectious agents ionizing radiation

8. Clinical manifestations Variable severity: asymptomatic to extremely ill time course: evolution over weeks, months, or years Systemic manifestations fever, night sweats, weight loss, anorexia, pruritis Local manifestations lymphadenopathy, splenomegaly most common any tissue potentially can be infiltrated

9. Other complications of lymphoma bone marrow failure (infiltration) CNS infiltration immune hemolysis or thrombocytopenia compression of structures (eg spinal cord, ureters) pleural/pericardial effusions, ascites

10. Diagnosis requires an adequate biopsy Diagnosis should be biopsy-proven before treatment is initiated Need enough tissue to assess cells and architecture –open bx vs core needle bx vs FNA

11. Stage IStage IIStage IIIStage IV Staging of lymphoma A: absence of B symptoms B: fever, night sweats, weight loss

12. Three common lymphomas Follicular lymphoma Diffuse large B-cell lymphoma Hodgkin lymphoma

13. Relative frequencies of different lymphomas Hodgkin lymphoma NHL Diffuse large B-cell Follicular Other NHL Non-Hodgkin Lymphomas ~85% of NHL are B-lineage

14. Follicular lymphoma most common type of “indolent” lymphoma usually widespread at presentation often asymptomatic not curable (some exceptions) associated with BCL-2 gene rearrangement [t(14;18)] cell of origin: germinal center B-cell

15. defer treatment if asymptomatic (“watch-and-wait”) several chemotherapy options if symptomatic median survival: years despite “indolent” label, morbidity and mortality can be considerable transformation to aggressive lymphoma can occur

16. Diffuse large B-cell lymphoma most common type of “aggressive” lymphoma usually symptomatic extranodal involvement is common cell of origin: germinal center B-cell treatment should be offered curable in ~ 40%

17. Hodgkin lymphoma

18. Classical Hodgkin Lymphoma

19. Hodgkin lymphoma cell of origin: germinal centre B-cell Reed-Sternberg cells (or RS variants) in the affected tissues most cells in affected lymph node are polyclonal reactive lymphoid cells, not neoplastic cells

20. Reed-Sternberg cell

21. RS cell and variants popcorn celllacunar cellclassic RS cell (mixed cellularity)(nodular sclerosis) (lymphocyte predominance)

22. A possible model of pathogenesis germinal centre B cell transforming event(s) loss of apoptosis RS cell inflammatory response EBV? cytokines

23. Hodgkin lymphoma Histologic subtypes Classical Hodgkin lymphoma –nodular sclerosis (most common subtype) –mixed cellularity –lymphocyte-rich –lymphocyte depleted

24. Epidemiology less frequent than non-Hodgkin lymphoma overall M>F peak incidence in 3rd decade

25. Associated (etiological?) factors EBV infection smaller family size higher socio-economic status caucasian > non-caucasian possible genetic predisposition other: HIV? occupation? herbicides?

26. Clinical manifestations: lymphadenopathy contiguous spread extranodal sites relatively uncommon except in advanced disease “B” symptoms