Lymphoma

Dr.Usha Dorairajan MS ,FRCSEd

Professor of Surgery

Kilpauk Medical College

Brevity in writing is the best insurance for its perusal. Rudolf Virchow

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

Non Hodgkin’s lymphoma

85%

Hodgkin’s lymphoma

15%

Type

Secondary lymphoid organs

Lymphatic OrgansPrimary lymphoid tissue

Incidence of lymphoma in India

INDIA

Male Female Both sexes

610618 570793 1181412

430.1 518.8 948.9

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 Information

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

Risk factors

• Age

• Sex

• Infectious agents

• Chemicals

• Genetics

• Immunodeficiency states autoimmune

• Cancer treatment

Infections

• Human T-lymphotrophic virus type1 adult T lymphoma

• Epstein-Barr (EBV) Burkitt’s Hodgkin’s

• 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

ExaminationWaldeyer’s ringNeckAxilla

Mediastinal wideningPleural effusion

Epitrochlear nodes

Abdomen liver, spleen,aortic iliac inguinal

Popliteal node

Mediastinal involvement common in nodular sclerosis Hodgkin’s lymphoma

•25 – 50% of NHL have extra nodal presentation

•GI tract 15%•Oropharyngeal 5-10%•CNS 5-10%

DiagnosisAccurate diagnosis of lymphoma depends on

Adequate tissue biopsy.

Immunohistochemistry Flow cytometry

Molecular and Genetic studies electrophoresis, Southern Blot, microarray PCRFISH

FNAC?

Immuno phenotyping

Lymph Node Biopsy

•Lymphoma

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.

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

Evaluation

•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

Reed Sternberg

cell

Hodgkin’s 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

Nodular sclerosis

•Lacunar cell Popcorn cell

•Nodular lymphocyte

•Predominant HL

Precursor Lymphoid NeoplasmsB lymphoblastic leukemia / lymphoma NOSB lymphoblastic leukemia / lymphoma with recurrent genetic abnormalitiesB lymphoblastic leukemia / lymphoma with t(9;22); bcr-abl1B lymphoblastic leukemia / lymphoma with t(v;11q23); MLL rearrangedB lymphoblastic leukemia / lymphoma with t(12:21); TEL-AML1 & ETV6-RUNX1B lymphoblastic leukemia / lymphoma with hyperploidyB lymphoblastic leukemia / lymphoma with hypodiploidyB lymphoblastic leukemia / lymphoma with t(5;14); IL3-IGHB lymphoblastic leukemia / lymphoma with t(1;19); E2A-PBX1 & TCF3-PBX1T lymphoblastic leukemia / lymphoma

Mature B-Cell NeoplasmsChronic lymphocytic leukemia / small lymphocytic lymphomaB-cell prolymphocytic leukemiaSplenic marginal zone lymphomaHairy cell leukemiaLymphoplasmacytic lymphoma / Waldenstrom macroglobulinemiaHeavy chain diseasePlasma cell myelomaSolitary plasmacytoma of boneExtraosseous plasmacytomaExtranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) typeNodal marginal zone lymphomaFollicular lymphomaPrimary cutaneous follicular lymphomaMantle cell lymphomaDiffuse 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 inflammationLymphomatoid granulomatosisPrimary mediastinal large B-cell lymphomaIntravascular large B-cell lymphomaALK+ large B-cell lymphomaPlasmablastic lymphomaLarge B-cell lymphoma associated with HHV8+ Castleman diseasePrimary effusion lymphomaBurkitt lymphomaB cell lymphoma, unclassifiable, Burkitt-likeB cell lymphoma, unclassifiable, Hodgkin lymphoma-like lymphoma

New WHO - REAL Classification of Lymphoid Neoplasms (2008)

Mature T-Cell & NK-Cell NeoplasmsT-cell prolymphocytic leukemiaT-cell large granular lymphocytic leukemiaChronic lymphoproliferative disorder of NK-cells.Aggressive NK-cell leukemiaSystemic EBV+ T-cell lymphoproliferative disorder of childhoodHydroa vacciniforme-like lymphomaAdult T-cell lymphoma/leukemiaExtranodal T-cell/NK-cell lymphoma, nasal typeEnteropathy-associated T-cell lymphomaHepato-splenic T-cell lymphomaSubcutaneous panniculitis-like T-cell lymphomaMycosis fungoidesSézary syndromePrimary cutaneous CD30+ T-cell lymphoproliferative disorderPrimary cutaneous gamma-delta T-cell lymphomaPeripheral T-cell lymphoma, NOSAngioimmunoblastic T-cell lymphomaAnaplastic large cell lymphoma, ALK+ typeAnaplastic large cell lymphoma, ALK- type

Lymph node structure

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

Individual cells are separated and examined.

  Flow cytometry

identifies types of lymphoma from FNAC specimens

Flow Cytometry

FNAC

• To diagnose relapse

• Flow cytometry possible with FNAC

• Inaccessible nodes like abdominal and retroperitoneal nodes can be targeted under CT guidance for FNAC

Why Immuno phenotyping

• To differentiate a lymphoma from poorly differentiated carcinoma

• To differentiate a lymphoma from a reactive lesion (monoclonal)

• Classification of lymphoma

Treatment of lymphoma

• Staging work Up

• Treatment

X-ray chest, CT chest and CT abdomen

•Bone marrow biopsy.

•PET scan

•MRI

•CSF analysis

Staging Work Up

Ann Arbor Staging

•A/B•A/B•A/B •A/B

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 cmThe number of anatomic regions involved should be indicated by a

subscript (eg, II3) Stage III1

Stage III2

Stage III may be subdivided into: III1, with or without splenic, hilar,

celiac, or portal nodes;III2, 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

The treatment and prognosis depends on stage patient performance status

the characteristic of lymphoma.

International Prognostic Indexfor Hodgkin’s 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

International Prognostic Indexfor Non Hodgkin’s lymphoma

• Age> 60 years

• Performance status>2

• LDH> than normal

• Ann Arbour stage III or IV

• > 2 Extranodal sites

Complete haemogram LFT and RFT patient characteristics glucose, calcium

Lactate Dehydrogenase (LDH) Albumin lymphoma characteristic β2 microglobulin

Treatment

Hodgkin’s lymphoma usually arises in lymph nodes and spreads to contiguous groups. Extranodal presentation are rare.

Treatment is by

stage of disease and prognostic factors

Treatment of lymphoma

• Treatment modality

radiotherapy

chemotherapy

combination therapy

high dose chemotherapy with bone marrow transplant

monoclonal antibody RITUXIMAB

Treatment of Hodgkin’s lymphoma

• With appropriate treatment about 85% of patients with Hodgkin disease are cured

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

Radiation therapy• Extended field

• mantle field

• paraaortic field

• pelvic field

• CURRENT TREND

• Involved field radiotherapy

• Neck

• Mediastinum

• Axilla

• Paraaortic

• inguinal

Complications of treatment

• Second malignancy

• Cardiac dysfunction

• Lung fibrosis

• sterility

•In Hodgkin’s disease current trend is

less aggressive treatment to minimise

complications

•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

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

Treatment of Non Hodgkin’s 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

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

HIV associated lymphoma

•HIV-associated, non-Hodgkin’s 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.

•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

Man’s mind once stretched by a new idea never regains it’s original dimensions

Oliver Wendell Holmes Jr

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).

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