1. L YMPHOMA FOR THE G ENERALIST Lee Berkowitz, MD

2. G OALS AND O BJECTIVES 1. Understand the importance of pathology and staging in the approach to management of patients with lymphoma. 2. Recognize that a lymph node biopsy is the correct procedure to diagnose lymphoma. 3. Appreciate that the approach to the management of patients with lymphoma is varied and idividualized.

3. N ON -H ODGKINS

4. E PIDEMIOLOGY 5 th most common cancer in adults Incidence is increasing 2-3% per year

5. P ATHOGENESIS 1. Immune suppression/dysregulation – HIV, organ transplant, RA, SCID 2. H. pylori – MALT 3. EBV – Burkitts, ? Hodgkins 4. HHV 8 – Castlemans 5. HTLV 1 – T cell leukemia, lymphoma 6. t(14;18) – follicular 7. t(11;14) – Mantle cell 8. t(8;14) - Burkitts

6. Pathology Staging

7. N ON -H ODGKINS The indolent lymphomas B-cell neoplasms Small lymphocytic lymphoma/B-cell chronic lymphocytic leukemia Lymphoplasmacytic lymphoma (± Waldenstrom's macroglobulinemia) Plasma cell myeloma/plasmacytoma Hairy cell leukemia Follicular lymphoma (grade I and II) Marginal zone B-cell lymphoma Mantle cell lymphoma T- cell neoplasms T-cell large granular lymphocyte leukemia Mycosis fungoides T-cell prolymphocytic leukemia Natural killer cell neoplasms Natural killer cell large granular lymphocyte leukemia The aggressive lymphomas B-cell neoplasms Follicular lymphoma (grade III) Diffuse large B-cell lymphoma Mantle cell lymphoma T-cell neoplasms Peripheral T-cell lymphoma Anaplastic large cell lymphoma, T/null cell The highly aggressive lymphomas B-cell neoplasms Burkitt's lymphoma Precursor B lymphoblastic leukemia/lymphoma T-cell neoplasms Adult T-cell lymphoma/leukemia Precursor T lymphoblastic

8. P ATHOLOGY Key aspects – follicular vs diffuse size of the cells in their normal environment

9. F OLLICULAR P ATTERN

10. D IFFUSE P ATTERN

11. P ATHOLOGY Nodal architecture The ONLY way to get this information is to biopsy or excise a node. A fine needle aspiration will not be adequate.

12. P ATHOLOGY Indolent Aggressive follicular grades I,II follicular grade III marginal zone diffuse large cell MALT mantle cell Burkitts

13. N ATURAL H ISTORY OF L YMPHOMAS Indolent(Follicular) – mean survival of 8 years Aggressive(Diffuse)– mean survival of 12 months Highly aggressive – mean survival of 8- 10 weeks

14. S TAGING I. 1 nodal group II. 2 nodal groups on the same side of the diaphragm III. Disease above and below the diaphragm IV. Disease in other organs

15. S TAGING Physical examination CT scans Bone marrow biopsies

16. S TAGING N ON -H ODGKINS Low –Grade I-II III- IV

17. S TAGING N ON -H ODGKINS Low-Grade I-II 5% III-IV 95%

18. S TAGING N ON -H ODGKINS Intermediate Grade I-II 30% III-IV 70%

19. I NTERNATIONAL P ROGNOSTIC I NDEX (IPI) D IFFUSE LYMPHOMAS Age>60 LDH> normal Performance status Stage III or IV Two or more extra nodal sites

20. IPI Risk Risk sum 5 yr survival % Low 0-1 73 Low –Interm 2 51 High –Interm 3 43 High 4-5 26

21. FOLLICULAR LYMPHOMA IPI Age>60 Stage III/IV LDH>normal Anemia 5 or more nodal sites

22. FLIPI Risk Risk score 10 yr survival Low 0-1 70% Interm 2 50% High 3 36%

23. T REATMENT L OW - GRADE 1. These cells over express bcl 2 2. The median survival for these patients untreated is 8 years

24. T REATMENT N ON -H ODGKINS L OW - GRADE 1. Observation 2. Standard chemo 3. Monoclonal antibodies – rituximab 4. Stem-cell transplants

25. T REATMENT N ON -H ODGKINS Intermediate and High-grade – Cure with chemotherapy

26. H ODGKINS

27. E PIDEMIOLOGY 8000 new patients per year Bimodal distribution – one peak at 30 years one peak at 50 years

28. P ATHOGENESIS - H ODGKINS 1. EBV 2 NF- kB ( nuclear factor kappa B)

29. H ODGKINS 1. Lymphocyte Predominant 2. Nodular Sclerosing 3. Mixed Cellularity 4. Lymphocyte Depleted

30. S TAGING H ODGKINS I. 15% II. 35% III.35% IV.15%

31. T REATMENT H ODGKINS Stage I – Cure with radiation therapy Stage II, III, IV – Cure with chemotherapy

32. W HEN T O S USPECT L YMPHOMA 1. Patients with impaired immune systems HIV, Transplant, Autoimmune diseases 2. Patients with unexplained fever, night sweats, weight loss 3. Patients with lymphadenopathy

33. L YMPHADENOPATHY Medicine 79:338 – 47, 2000 Biopsy or not Neg Positive Tenderness Generalized Pruritus Size < 1cm Supraclavicular Hard Size > 2 cm