Large cell immunoblastic Diffuse histiocytic (DHL) Lymphoblastic lymphoma Diffuse lymphoblastic Small non cleaved cell Burkitt s Non- Burkitt s

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1 Non Hodgkin s Lymphoma Introduction 6th most common cause of cancer death in United States. Increasing in incidence and mortality. Since 1970, the incidence of has almost doubled. Overview The types of non- Hodgkin s reflect the developmental stages of lymphocytes. Each type of can be viewed as a lymphocyte arrested at a certain stage of development and transformed into a malignant cell. 85% B cell origin, the rest T or null cell B cell differentiation Types of Classification of Non Hodgkin Lymphoma Indolent (low grade) Intermediate Aggressive (high grade) 1. Life expectancy in years, untreated % present in Stage III or IV 3. Incurable Working formulae Small lymphocytic Low Grade 1. Life expectancy in weeks, untreated 2. Potentially curable Rappaport Diffuse well- differentiated lymphocytic (DWDL or WDLL) Commonly used classification Intermediate Grade Follicular small cleaved Follicular mixed Follicular large cell Diffuse small cleaved cell Diffuse mixed Diffuse large cell Nodular poorly differentiated lymphocytic (NPDL) Nodular mixed lymphocytic- histiocytic (NM) Nodular histiocytic (NH) Diffuse poorly differentiated lymphocytic (DPDL) Diffuse mixed lymphocytic- histiocytic (DM) Diffuse histiocytic (DHL) The REAL Classification (Revised European- American Lymphoma Classification) nb Large cell immunoblastic Diffuse histiocytic (DHL) High Grade Lymphoblastic Diffuse lymphoblastic Small non cleaved cell Burkitt s Non- Burkitt s Diffuse undifferentiated (DU) Not included in these classification o Mantle cell o Mycosis fungoides o Peripheral T cell o Marginal zone B cell à MALT o Angioimmunoblastic 1. Precursor B- lymphoblastic /leukemia 13. Primary mediastinal large B cell 2. B cell CLL/prolymphocytic leukemia/small lymphocytic 14. Burkitt s leukemia 15. High grade B cell, Burkitt- like 3. Lymphoplasmacytoid 16. Precursor T lymphoblastic /leukemia 4. Mantle cell 17. T cell CLL/prolymphocytic leukemia 5. Follicular center, follicular 18. Large cell granular lymphocytic leukemia: T cell type, NK 6. Follicular center, diffuse cell type 7. Extranodal marginal zone B cell (MALT type) 19. Mycosis fungoides/ Sézary syndrome 8. Nodal marginal zone B cell 20. Peripheral T cell s, unspecified 9. Splenic marginal zone B- cell 21. Hepatosplenic T cell 10. Hairy cell leukemia 22. Angioimmunoblastic T cell 11. Plasmacytoma/myeloma 12. Diffuse large B cell *refer lecture for WHO classification 3 different categories of Aggressive Lymphoma: 1. Activated B cell like diffuse large B cell 2. Germinal center B cell like diffuse large B cell 3. Primary mediastinal B cell

2 Diagnosis of NHL Staging workup Staging: Ann Arbor International Index for NHL staging Indolent Aggressive *refer lecture for this à nb Excisional biopsy is preferred to show nodal architecture (follicular vs diffuse). Immunohistochemistry to confirm cells are lymphoid Ø LCA (leukocyte common antigen) Ø Monoclonal staining with Igk or Igl Flow cytometry: Ø CD 19, CD20 for B cell s Ø CD 3, CD 4, CD8 for T cell s Chromosome changes Ø 14;18 translocation in follicular à bcl- 2 oncogene Ø t(8;14), t(2;8), t(8;22) in Burkitt s à c- myc oncogene Ø t(11;14) in mantle cell à cyclin D1 gene CBC, chemistries, urinanalysis CT scans of chest, abdomen and pelvis Bone marrow biopsy and aspirate (Lumbar puncture) AIDS T cell lymphoblastic High grade with positive marrow *staging laparotomy and lymphangiogram are not indicated in NHL I 1 lymph node region or structure II >1 lymph node region or structure, same side of diaphragm III Both sides of diaphragm IV Extranodal sites beyond E designation subssripts: A, B, E, S Older than 60 yo Adverse risk Stage III or IV factors 2 extranodal sites performance score >2 LDH > normal Risk category Low High intermediate Low intermediate High No of risk factors 0, , 5 Treatment TTT options Small lymphocytic, follicular small cleaved, follicular mixed small,large à follicular grade 1, % in Stage I or II 85-90% Stage III or IV potentially curable incurable local radiotherapy treatment does not prolong survival Reasons to treat Constitutional symptoms Cosmetic considerations in advanced Anatomic obstruction Painful lymph nodes indolent Organ dysfunction Cytopenias TTT options in advanced indolent R CHOP chemotherapy TTT options TTT options for early stage TTT options for advanced stage 1. Observation only. 2. Radiotherapy to site of problem. 3. Systemic chemotherapy a. oral agents: chlorambucil and prednisone b. IV agents: CHOP, COP, fludarabine, 2- CDA. 4. Antibody against CD20: Rituxan, Bexxar, Zevalin. 5. Stem cell or bone marrow transplant. Cyclophosphamide (Cytoxan) Hydroxydaunorubicin (Adriamycin) Oncovin (vincristine) Prednisone Rituximab Subtybes included Diffuse large B cell (DLBCL) DLBCL coexistent with o follicular of any grade o gastric MALT o non gastric MALT Follicular Lymphoma grade 3 Intravascular largae B cell DLBCL associated with chronic inflammation ALK positive DLBCL EBV positive DLBCL of the elderly T cell. histiocyte rich large B cell Stage I or II Effect of adding Rituximab to 3 cycles of CHOP + involved field radiotherapy for limited stage aggressive DLBCL : Result * theres info left out at slide 27, 30-35, 38-41, 43, 54à go n look for it. sorry CHOP Rituximab is standard initial therapy for ALL patients with advanced stage, diffuse Large B cell Subtypes not included Cutaneous B Cell Primary DLBCL of the CNS potentially curable disseminates through bloodstream early must use systemic chemotherapy R- CHOP x 6 cycles R- CHOP x 3 cycles followed by radiotherapy In a comparison of studies, poor risk patients experienced a PFS benefit with the addition of Rituximab to CHOP Similarly, OS was also improved with the addition of Rituximab to CHOP Despite the lack of prospective randomized data, R CHOP has become the standard of care for these patients

3 Lymphoblastic T cell malignancy. Male adolescents. Mediastinal mass. T cell variant of T cell acute lymphoblastic leukemia. Prognosis improving with intensive ALL regimens. African variety: jaw tumor, strongly linked to Epstein- Barr Virus infection. In U.S., about 50% EBV infection. Burkitt s Lymphoma May present as abdominal mass. Most rapidly growing human tumor. Typical chromosome abnormality: c- myc oncogene linked to one of the immunoglobulin genes. Treated with multidrug regimen similar to pediatric leukemia/ regimens Mycosis Fungoides Malignancy of helper T cells. Affinity for skin. Can be treated with electron beam radiation, ultraviolet light, or topical alkylating agents. Adult T cell Associated with HTLV- I infection. Leukemia - Caribbean, southeastern U.S. Lymphoma Hepatosplenomegaly, leukocytosis, lymphadenopathy, skin involvement, lytic lesions of bone, hypercalcemia. May respond to AZT and interferon. Aggressive s of B cell origin. AIDS Lymphoma Burkitt s, Burkitt s- like, and large cell immunoblastic. Treatment often limited by immune compromise of the patient. Prognosis improved with HAART therapy. Mucosa- Associated Lymphoid Tissue Chronic infection of the stomach by Helicobacter pylori. MALT Lymphoma Localized to the stomach, indolent course. Can be cured in many cases by antibiotics against H. pylori.

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