LYMPHOMA FOR THE GENERALISTLee Berkowitz, MD

GOALS AND OBJECTIVES

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.

NON-HODGKINS

EPIDEMIOLOGY

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

PATHOGENESIS

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

NON-HODGKINS 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

PATHOLOGY

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

FOLLICULAR PATTERN

DIFFUSE PATTERN

PATHOLOGY

Nodal architecture The ONLY way to get this information

is to biopsy or excise a node. A fine needle aspiration will not be adequate.

PATHOLOGY

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

NATURAL HISTORY OF LYMPHOMAS

Indolent(Follicular) – mean survival of 8 years Aggressive(Diffuse)– mean survival of 12

months Highly aggressive – mean survival of 8- 10

weeks

STAGING

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

STAGING

Physical examination CT scans Bone marrow biopsies

STAGING NON-HODGKINS

Low –Grade I-II III- IV

STAGING NON-HODGKINS

Low-Grade I-II 5% III-IV 95%

STAGINGNON-HODGKINS

Intermediate Grade I-II 30% III-IV 70%

INTERNATIONAL PROGNOSTIC INDEX(IPI) DIFFUSE 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 0-1 73 Low –Interm 2 51 High –Interm 3 43 High 4-5 26

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

FLIPI

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

TREATMENT LOW-GRADE

1. These cells over express bcl 2 2. The median survival for these patients

untreated is 8 years

TREATMENTNON-HODGKINS LOW-GRADE

1. Observation 2. Standard chemo 3. Monoclonal antibodies – rituximab 4. Stem-cell transplants

TREATMENTNON-HODGKINS

Intermediate and High-grade – Cure with chemotherapy

HODGKINS

EPIDEMIOLOGY

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

PATHOGENESIS - HODGKINS

1. EBV 2 NF- kB ( nuclear factor kappa B)

HODGKINS

1. Lymphocyte Predominant2. Nodular Sclerosing3. Mixed Cellularity4. Lymphocyte Depleted

STAGINGHODGKINS

I. 15% II. 35% III.35% IV.15%

TREATMENTHODGKINS

Stage I – Cure with radiation therapy Stage II, III, IV – Cure with chemotherapy

WHEN TO SUSPECT LYMPHOMA

1. Patients with impaired immune systems HIV, Transplant, Autoimmune diseases 2. Patients with unexplained fever, night

sweats, weight loss 3. Patients with lymphadenopathy

LYMPHADENOPATHY

Medicine 79:338 – 47, 2000 Biopsy or not

Neg Positive Tenderness Generalized Pruritus Size < 1cm Supraclavicular Hard Size > 2 cm