1. Malignancies of lymphoid cells ↑ incidence in general …. CLL is the most common form leukemia in US: Incidence in 2007: 15,340 Origin of Hodgkin lymphoma is B cell lymphocytes, 2 peak of age: 20-30 yo & 70-80 yo Etiology & Epidemiology (1):

2. Etiology & Epidemiology (2): Role of EBV in HL: 20-40% mono or oligo- clonal Role of HIV in HL ↑ incidence of NHL 4% / year Principal predisposing factor is immunodeficiency

3. Etiology (3) Immunodeficiencies: -Primary: Kleinfelter syn, Chediak-Higashi, Wiscoth-Aldrich, Ataxia- telangiectasia syn -Secondary: Viruses: HIV,HTLV1, EBV, CMV, HBV, HCV, HHV8 Bacterias: H pylori Collagen- vascular diseases: Sjogren syn, RA, SLE Toxin or drugs: Organophosphores, Phenytoin, Radiation, prior chemotherapy

4. Epidemiology (4) NHL 62%: -31% DLBCL -22% FL -7% Malt -7% T cell lymphoma -6% MCL Plasma cell dis 16% CLL 9% HL 8% ALL 4% Proportional prevalence

5. Pathogenesis Histology RS cells Place of IHC Cytology Molecular findings

6. Role & place of genetics in lymphomas DiseaseCytogenetic abOncogene FLt (14,18)BCL2 MCLt (11,14)BCL1 Burkitt s dis.t (8,-)C-MYC DLBCLt (3,-) t (17,-) BCL6 P53

7. Clinical findings Most symptomatic patients have enlarged lymph nodes (more commonly cervical and supraclavicular) and/or splenomegaly The lymph nodes are usually discrete, freely movable, and nontender Hepatomegaly may occure Less common manifestation are infiltration of tonsils, mesenteric or retroperitoneal lymphadenopathy, and skin infiltration Patients rarely present with features of anemia, and bruising or bleeding B signs

8. Laboratory findings CBC LDH Β 2 microglobulines Serum albumine & ESR in HL Serum prot electrophoresis: Hypogammaglobulinemia is often observed Viruses & systemic dis evaluation

9. Differential diagnosis Infectious causes –bacterial (tuberculosis) –viral (mononucleosis) Malignant causes –Solid tumors

10. Investigations Pretreatment studies of patients with lymphoma should include examination of: –complete blood count –peripheral blood smear –reticulocyte count –renal and liver function tests –serum protein electrophoresis –immunoglobulin levels –LDH –plasma  2 microglobulin level Bone marrow biopsy Echocardiography

11. Staging Ann Arbor Classification –I –II –III –IV –A vs B

12. Prognosis IPI for DLBCL: -Age ≥ 60 -LDH -Stage III & IV -PS ≥ 2 -≥ extranodal involvement 0 fac: 5 y survival > 73% 4,5 fac: 5 y survival < 26%

13. Treatment –Alkylating agents (chlorambucil, cyclophosphamide) –Anthracyclines –Glucocorticoides –Monoclonal antibodies –Bone marrow transplantation –And systemic complications requiring therapy antibiotics immunoglobulin steroids blood products