LYMPHOMAS

WHO Lymphoid Neoplasms

B cell neoplasms T/NK cell neoplasms Hodgkin lymphoma (disease)

2008 Estimated US Cancer Cases*

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2008.

Men720,280

Women679,510

31% Breast

12% Lung & bronchus

11% Colon & rectum

6% Uterine corpus

4% Non-Hodgkin lymphoma

4% Melanoma of skin

3% Thyroid

3% Ovary

2% Urinary bladder

2% Pancreas

22% All Other Sites

Prostate 33%

Lung & bronchus 13%

Colon & rectum 10%

Urinary bladder 6%

Melanoma of skin 5%

Non-Hodgkin 4% lymphoma

Kidney 3%

Oral cavity 3%

Leukemia 3%

Pancreas 2%

All Other Sites 18%

Lymphoma Clonal malignant disorders that are derived

from lymphoid cells: either precursor or mature T-cell or B-cell

Majority are of B- cell origin

Divided into 2 main types : 1. Hodgkin’s lymphoma 2. Non - Hodgkin’s lymphoma

Hodgkin’s Disease

Histologically & clinically a distinct malignant disease

Predominantly, B-cell disease Course of the disease is variable,

but the prognosis has improved with modern treatment

B cell malignancies

Pre-B acute lympho-

blastic leukemia

B cell lymphoma Chronic lympho-

cytic leukemia

Multiple myeloma

Progressive B lymphocyte maturation

Bone marrow

Lymph node,

lymph, blood,

bone marrow

Lymph node,

lymph, blood,

bone marrowBone marrow

Lymphoid stem cell Maturing B cellmany stages

Mature B cell Plasma cell

Clinical features Bimodal age distribution :

young adults ( 20-30 yrs) & elderly (> 50yrs) may occur at any age

M > F Lymphadenopathy:

most often cervical region asymmetrical, discretepainless, non-tenderelastic character on palpation ( rubbery)not adherent to skin

Constitutional symptoms ( B symptoms )Night sweats, sustained fever > 38 degree celsius, loss of weight >10% of body weight in 6 mo

Fever sometimes cyclical (‘Pel-Ebstein fever’) Pain at the site of disease after drinking

alcohol Pallor Pruritis Symptoms of Bulky (>10 cm) disease

Lymph node biopsy :

Malignant REED-STERNBERG ( RS) Cell: Bi-nucleate cell with a prominent nucleolus. Derived from B cell, at an early stage of differentiation

Reactive background of eosinophils, lymphocytes, plasma cells

Fibrous tissue

REED-STERNBERG ( RS ) Cell

Hodgkin’s Disease/LymphomaIn the Beginning

Accounts for ~ 30% of all malignant lymphomas

Composed of two different disease entities:

Lymphocyte-predominant Hodgkin’s (LPHD), making up ~ 5% of cases

Classical HD, representing ~ 95% of all HDs.

A common factor of both HD types is that neoplastic cells constitute only a small minority of the cells in the affected tissue, often corresponding to < 2% of the total tumor

Fatal disease with 90% of untreated patients dying within 2 to 3 years

With chemotherapy, >80% of patients suffering from HD are cured.

Pathogenesis of HD is still largely unknown.

HD nearly always arises and disseminates in lymph nodes

Hodgkin’s Disease/LymphomaIn the Beginning

Hodgkin’s Disease/LymphomaClinical Presentation

Stage Definition

I Involvement of a single lymph node region (I) or of a single extralymphatic organ or site (IE)

II Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of an extralymphatic organ or site and one or more lymph node regions on the same side of the diaphragm (IIE)

III Involvement of lymph node regions on both sides of the diaphragm (III) which may be accompanied by involvement of the spleen (IIIS) or by localized involvement of an extralymphatic organ or site (IIIE) or both (IIISE)

IV Diffuse or disseminated involvement of one or more extra lymphatic organs or tissues with or without associated lymph node involvement

B symptoms: fever > 38ºC for three consecutive days, drenching night sweats or unexplained loss 10% or more of weight the preceding 6 months

Non Hodgkin’s lymphoma

Incidence is increasing NHL>HD Median age of presentation is 65-70 yrs M>F More often clinically disseminated at

diagnosis B-cell-70% ; T-cell-30%

Staging Stage I : Involvement of single LN region (I) or

extra lymphatic site (IAE ) Stage II : Two or more LN regions involved (II)

or an extra lymphatic site and lymph node regions on the same side of diaphragm

Stage III : Involvement of lymph node regions on both sides of diaphragm, with (IIIE) or without (III) localized extra lymphatic involvement or involvement of the spleen (IIS) or both (IISE)

Stage IV : Involvement outside LN areas (Liver, bone marrow)

A : Absence of ‘B’ symptoms B : B symptoms present

Clinical features Widely disseminated at presentation Nodal involvement:

Painless lymphadenopathy, often cervical region is the most common presentation

Hepatosplenomegaly Extranodal : Intestinal lymphoma ( abdominal pain,

anemia, dysphagia); CNS ( headache, cranial nerve palsies, spinal cord compression) ;

Skin, Testis; Thyroid; Lung Bone marrow (low grade): Pancytopenia

Systemic symptomsSweating, weight loss, itchingMetabolic complications:

hyperuricemia, hypercalcemia, renal failure

Compression syndrome:Gut obstructionAscites

Diagnosis and staging

Similar to HD plus, Bone marrow aspirate & trephine Immunophenotyping : Monoclonal antibodies

directed against specific lymphocyte associated antigens B cell antigens ( CD 19, 20, 22); T cell antigens ( CD 2, 3, 5 & 7)

Immunoglobulin determination: IgG / IgM praprotein marker

HIV

Non-Hodgkin’s LymphomaRappaport Classification

Small cell, follicular Small cell, diffuse Large cell, follicular Large cell, diffuse

Non-Hodgkin’s LymphomaRappaport Classification

Nodular (follicular) Diffuse

Small cell Large cell

Indolent Aggressive

Classification

Low grade

Proliferation: LowCourse:

IndolentSymptoms: -veTreatment: Not

curable

High grade

HighRapid, fatal(un-

Rx)+vePotentially

Curable

StagingSimilar to HD

Etiology Cannot be attributed a single cause Chromosomal translocations: t (14, 18)

Infection:Virus:EBV, HTLV,HHV-8, HIVBacteria: H.Pylori - Gastric lymphoma

Immunology: Congenital immunodeficiency, Immunocompromised patients - HIV, organ

transplantation

Non-Hodgkin’s LymphomaImmunophenotyping

Immunohistochemistry Immunofluorescence Flow cytometry

Identification of CD’s (cluster determinants) CD5 = T cell type CD20 = B cell type

Non-Hodgkin’s LymphomaBurkitt’s NHL

Very Aggressive Curable with standard-dose therapy but

requires very extensive chemotherapy protocol Translocation t(8,14) Specific Hematopathology Finding

Starry, Starry Night

Burkitt’s LymhomaStarry, Starry Night

- Burkitt’s Lymphoma –Background

* Burkitt's lymphoma (BL) is a tumor which was first described in 1958 by Denis Burkitt, a surgeon working in Africa. It is a solid tumor of B Lymphocytes which form part of the white cell population in the blood and lymph glands. It is one form of non-Hodgkin's lymphoma.

- Burkitt’s Lymphoma -Karyotype:

* Here is an actual karyotype (courtesy of Janet Finan and C. M. Croce) of a cell from the tumor of a patient with Burkitt's lymphoma. The long (q) arm of the resulting chromosome 8 is shorter (8q-) than its normal homologue; the long arm of translocated chromosome 14 longer (14q+).

 

- Burkitt’s Lymphoma -Incidence

The incidence of Burkitt's lymphoma shows great geographical variation. It is the most common childhood tumor in equatorial Africa but is very rare in children in Western countries. Recently Burkitt's lymphoma has been diagnosed in around 2% of AIDS patients.

Males are three times more likely to suffer from othis disorder as opposed to females.

Burkitt’s is a rare form of cancer and there are only about 100 new cases each year in the United States.  

- Burkitt’s Lymphoma -Causes

* In almost all cases of African Burkitt's lymphoma the cells carry a virus known as Epstein-Barr virus (EBV) named after the two British scientists who discovered it.

 * This virus is very common and over 90% of adults throughout the world have evidence of past infection. Clearly not everyone develops the tumour and so EBV alone does not cause Burkitt's lymphoma. It must be only one of the factors necessary for the disease to develop.

* Other possible contributory factors are chronic malaria infection in Africa and infection with the AIDS virus (human immunodeficiency virus - HIV) in Western countries.