L YMPHOMA FOR THE G ENERALIST Lee Berkowitz, MD

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.

N ON -H ODGKINS

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

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

Pathology Staging

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

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

F OLLICULAR P ATTERN

D IFFUSE P ATTERN

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.

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

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 weeks

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

S TAGING Physical examination CT scans Bone marrow biopsies

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

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

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

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

IPI Risk Risk sum 5 yr survival % Low Low –Interm 2 51 High –Interm 3 43 High

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

FLIPI Risk Risk score 10 yr survival Low % Interm 2 50% High 3 36%

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

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

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

H ODGKINS

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

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

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

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

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

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

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