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Lymphoma Dr.Usha Dorairajan MS,FRCSEd Professor of Surgery Kilpauk Medical College Brevity in writing is the best insurance for its perusal. Rudolf Virchow.

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Presentation on theme: "Lymphoma Dr.Usha Dorairajan MS,FRCSEd Professor of Surgery Kilpauk Medical College Brevity in writing is the best insurance for its perusal. Rudolf Virchow."— Presentation transcript:

1 Lymphoma Dr.Usha Dorairajan MS,FRCSEd Professor of Surgery Kilpauk Medical College Brevity in writing is the best insurance for its perusal. Rudolf Virchow


3 A malignant neoplasm of B or T lymphocytes, arising from a monoclonal proliferation of lymphocytes; McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc. Lymphoma


5 Non Hodgkins lymphoma 85% Hodgkins lymphoma 15% Type

6 Secondary lymphoid organs Lymphatic Organs Primary lymphoid tissue

7 Incidence of lymphoma in India INDIA Male FemaleBoth sexes 6106185707931181412 430.1518.8948.9 Population (thousands) Number of new cancer cases (thousands) Cancer Lip, oral cavity Nasopharynx Stomach Colorectum Hodgkin lymphoma Non-Hodgkin lymphoma Incidence 69820 3333 35059 36476 7371 23718 Mortality 47653 2412 33564 25690 3587 16243 GLOBOCAN 2008 GLOBOCAN 2008 (IARC) Section of Cancer InformationSection of Cancer Information

8 Symptoms 1.Painless lymphadenopathy cervical axilla or groin 2. Weight loss 3. Fever 4. drenching sweating at night 5. Pruritis 6. Loss of appetite 7. A feeling of weakness 8. Breathlessness along with edema of the face and neck

9 Risk factors Age Sex Infectious agents Chemicals Genetics Immunodeficiency states autoimmune Cancer treatment

10 Infections Human T-lymphotrophic virus type1 adult T lymphoma Epstein-Barr (EBV) Burkitts Hodgkins Helicobacter pylori MALT lymphomas of the stomach; Human immunodeficiency virus (HIV), HHV-8 (Human Herpes virus) Primary effusion lymphoma Hepatitis C virus B-NHL DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology, Eighth Edition

11 Examination Waldeyers ring Neck Axilla Mediastinal widening Pleural effusion Epitrochlear nodes Abdomen liver, spleen, aortic iliac inguinal Popliteal node

12 Mediastinal involvement common in nodular sclerosis Hodgkins lymphoma

13 25 – 50% of NHL have extra nodal presentation GI tract 15% Oropharyngeal 5-10% CNS 5-10%

14 Diagnosis Accurate diagnosis of lymphoma depends on Adequate tissue biopsy. Immunohistochemistry Flow cytometry Molecular and Genetic studies electrophoresis, Southern Blot, microarray PCR FISH FNAC? Immuno phenotyping

15 Lymph Node Biopsy Lymphoma

16 Lymph node biopsy Biopsy of easily accessible largest node. A complete node is best. And more than one node Axilla and groin are avoided. To be delivered immediately without fixation to path lab. Cell suspensions of fresh tissue for flow cytometry immunotyping, cell kinetics analysis and molecular analysis. Touch imprint cytology is for comparing bone marrow and nodal cytology. A portion is snap frozen for molecular genetics and for immunohistochemistry. A portion is fixed and processed for morphological study.

17 Diagnosis of NHL lymphoma depends on finding abnormal numbers of lymphocytes that are destroying normal architecture of lymphoid tissue or invading non lymphoid tissue or both. Evaluation

18 Hodgkin lymphoma –Classification Nodular lymphocyte-predominant Hodgkin lymphomas Classic Hodgkin lymphomas Nodular sclerosis Hodgkin lymphoma Lymphocyte-rich classic Hodgkin lymphoma Mixed cellularity Hodgkin lymphoma Lymphocyte depletion Hodgkin

19 Reed Sternberg cell Hodgkins lymphoma contain one of the characteristic Reed Sternberg cells and mononuclear malignant cells Hodgkin cell) HRS cells In a background of non neoplastic cells. HRS cells form only.1% - 1.5% of cellular population

20 Nodular sclerosis Lacunar cell Popcorn cell Nodular lymphocyte Predominant HL

21 Precursor Lymphoid Neoplasms B lymphoblastic leukemia / lymphoma NOS B lymphoblastic leukemia / lymphoma with recurrent genetic abnormalities B lymphoblastic leukemia / lymphoma with t(9;22); bcr-abl1 B lymphoblastic leukemia / lymphoma with t(v;11q23); MLL rearranged B lymphoblastic leukemia / lymphoma with t(12:21); TEL-AML1 & ETV6-RUNX1 B lymphoblastic leukemia / lymphoma with hyperploidy B lymphoblastic leukemia / lymphoma with hypodiploidy B lymphoblastic leukemia / lymphoma with t(5;14); IL3-IGH B lymphoblastic leukemia / lymphoma with t(1;19); E2A-PBX1 & TCF3-PBX1 T lymphoblastic leukemia / lymphoma Mature B-Cell Neoplasms Chronic lymphocytic leukemia / small lymphocytic lymphoma B-cell prolymphocytic leukemia Splenic marginal zone lymphoma Hairy cell leukemia Lymphoplasmacytic lymphoma / Waldenstrom macroglobulinemia Heavy chain disease Plasma cell myeloma Solitary plasmacytoma of bone Extraosseous plasmacytoma Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type Nodal marginal zone lymphoma Follicular lymphoma Primary cutaneous follicular lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma, NOS (T-cell / histiocyte-rich type; primary CNS type ; primary leg skin type & EBV+ elderly type) Diffuse large B-cell lymphoma with chronic inflammation Lymphomatoid granulomatosis Primary mediastinal large B-cell lymphoma Intravascular large B-cell lymphoma ALK+ large B-cell lymphoma Plasmablastic lymphoma Large B-cell lymphoma associated with HHV8+ Castleman disease Primary effusion lymphoma Burkitt lymphoma B cell lymphoma, unclassifiable, Burkitt-like B cell lymphoma, unclassifiable, Hodgkin lymphoma-like lymphoma New WHO - REAL Classification of Lymphoid Neoplasms (2008)

22 Mature T-Cell & NK-Cell Neoplasms T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Chronic lymphoproliferative disorder of NK-cells. Aggressive NK-cell leukemia Systemic EBV+ T-cell lymphoproliferative disorder of childhood Hydroa vacciniforme-like lymphoma Adult T-cell lymphoma/leukemia Extranodal T-cell/NK-cell lymphoma, nasal type Enteropathy-associated T-cell lymphoma Hepato-splenic T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Mycosis fungoides Sézary syndrome Primary cutaneous CD30+ T-cell lymphoproliferative disorder Primary cutaneous gamma-delta T-cell lymphoma Peripheral T-cell lymphoma, NOS Angioimmunoblastic T-cell lymphoma Anaplastic large cell lymphoma, ALK+ type Anaplastic large cell lymphoma, ALK- type

23 Lymph node structure

24 The cells are examined to determine what antigens are expressed on the surface of the cells by using antibodies that bind to those antigens. Helps determine the type of lymphoma with far greater accuracy than just examining the biopsy under the microscope. A chart of which antigens are typically positive or negative is on CD chart.( Cluster Differentiation ) Immunohistochemistry

25 Individual cells are separated and examined. Flow cytometry identifies types of lymphoma from FNAC specimens Flow Cytometry

26 FNAC To diagnose relapse Flow cytometry possible with FNAC Inaccessible nodes like abdominal and retroperitoneal nodes can be targeted under CT guidance for FNAC

27 Why Immuno phenotyping To differentiate a lymphoma from poorly differentiated carcinoma To differentiate a lymphoma from a reactive lesion (monoclonal) Classification of lymphoma

28 Treatment of lymphoma Staging work Up Treatment Staging work Up Treatment

29 X-ray chest, CT chest and CT abdomen Bone marrow biopsy. PET scan MRI CSF analysis Staging W ork Up

30 Ann Arbor Staging A/B

31 Cotswold modifications X Massive mediastinal disease has been defined by the Cotswold meeting as a thoracic ratio of maximum transverse mass diameter greater than or equal to 33% of the internal transverse thoracic diameter measured at the T5/6 intervertebral disc level on chest radiography.or 10 cm The number of anatomic regions involved should be indicated by a subscript (eg, II 3 ) Stage III 1 Stage III 2 Stage III may be subdivided into: III 1, with or without splenic, hilar, celiac, or portal nodes; III 2, with para-aortic, iliac, mesenteric nodes CS \ PS CR Staging should be identified as clinical stage (CS) or pathologic stage (PS) A new category of response to therapy, unconfirmed/uncertain complete remission (CR) can be introduced because of the persistent radiologic abnormalities of uncertain significance

32 The treatment and prognosis depends on stage patient performance status the characteristic of lymphoma.

33 International Prognostic Index for Hodgkins lymphoma 1- Serum albumin < 4 gm/dl 2- Hemoglobin level below 10.5 gm/dl 3- Male gender 4- Stage IV disease 5- Age 45 years 6- WBC of 15,000/mm²7- Lymphocyte count 600/mm² or 8% of WBC

34 International Prognostic Index for Non Hodgkins lymphoma Age> 60 years Performance status>2 LDH> than normal Ann Arbour stage III or IV > 2 Extranodal sites

35 Complete haemogram LFT and RFT patient characteristics glucose, calcium Lactate Dehydrogenase (LDH) Albumin lymphoma characteristic β 2 microglobulin

36 Treatment

37 Hodgkins lymphoma usually arises in lymph nodes and spreads to contiguous groups. Extranodal presentation are rare. Treatment is by stage of disease and prognostic factors

38 Treatment of lymphoma Treatment modality radiotherapy chemotherapy combination therapy high dose chemotherapy with bone marrow transplant monoclonal antibody RITUXIMAB

39 Treatment of Hodgkins lymphoma With appropriate treatment about 85% of patients with Hodgkin disease are cured

40 Treatment of Hodgkin Lymphoma Radiation therapy alone in special circumstances Chemoradiotherapy ABVD for two to four cycles plus involved field radiotherapy(20 Gy or 30 Gy). Chemotherapy alone ABVD for four to six to eight cycles. (ABVD: doxorubicin plus bleomycin plus vinblastine plus dacarbazine BEACOPP (increased dose). (bleomycin plus etoposide plus doxorubicin plus cyclophosphamide plus vincristine plus procarbazine plus prednisone

41 Radiation therapy Extended field mantle field paraaortic field pelvic field CURRENT TREND Involved field radiotherapy Neck Mediastinum Axilla Paraaortic inguinal

42 Complications of treatment Second malignancy Cardiac dysfunction Lung fibrosis sterility In Hodgkins disease current trend is less aggressive treatment to minimise complications

43 Chemotherapy, radiotherapy and combined modality for Hodgkin's disease, with emphasis on second cancer risk Cochrane Reviews For early-stage patients chemoradiotherapy resulted in longer survival and longer HD-free survival than either RT or CT alone Second malignancy (SM) risk was lower with CRT than with RT For advanced stages no difference in survival between CRT and CT alone was established

44 Treatment of non-Hodgkin lymphoma (NHL) depends on the histologic type and stage.

45 Treatment of Non Hodgkins lymphoma Watchful waiting Chemotherapy with radiation therapy. Rituximab, an anti-CD20 monoclonal antibody, either alone or in combination with chemotherapy. R-CHOP (four to eight cycles). R-CHOP (three to eight cycles) plus IF-XRT. Autologous BMT or peripheral stem cell transplantation or allogeneic BMT for patients at high risk of relapse is under clinical evaluation

46 Cochrane Summary improved survival of follicular and in mantle cell lymphoma when treated with R-chemo compared to chemotherapy alone. no benefit for high-dose chemotherapy with stem cell transplantation as a first line treatment in patients with aggressive NHL. IFN as maintenance therapy for FL improves progression-free survival. A net benefit for overall survival is less evident

47 HIV associated lymphoma HIV-associated, non-Hodgkins lymphoma occurs in 5-10% of individuals with HIV infection virtually all of B-cell origin. Most are intermediate- or high-grade lymphomas Complete response occurs in 33-62% of patients. Relapse occurs in 25% of complete responders within 6 months. Median survival is 4-8 months, with about half dying of lymphoma and half of opportunistic infection.

48 Lymphoma is the most common small bowel malignancy in the pediatric age 50-93% of patients have intestinal lymphomas located in the ileocecal region. a history of nonspecific chronic abdominal pain common can present acutely as appendicitis or intussusception

49 Mans mind once stretched by a new idea never regains its original dimensions Oliver Wendell Holmes Jr

50 Summary Management of lymphoma needs a multidisciplinary approach with a need to keep abreast of evidence based medicine. Lymphoma is associated with immuno compromised states Surgeon s role in diagnosis of lymphoma. In treatment of lymphoma in extranodal sites (GI tract emergencies).

51 Coral.doc @

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