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

Men 720,280 Women 679,510

Prostate Lung & bronchus Colon & rectum Urinary bladder Melanoma of skin Non-Hodgkin lymphoma Kidney Oral cavity Leukemia Pancreas All Other Sites 33% 13% 10% 6% 5% 4% 3% 3% 3% 2% 18% 31% 12% 11% 6% 4% 4% Breast Lung & bronchus Colon & rectum Uterine corpus Non-Hodgkin lymphoma Melanoma of skin 3% Thyroid 3% 2% 2% 22% Ovary Urinary bladder Pancreas All Other Sites

*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.

Source: American Cancer Society, 2008.

  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

   Histologically & clinically a distinct malignant disease Predominantly, B-cell disease Course of the disease is variable, but the prognosis has improved with modern treatment

Bone marrow Lymph node, lymph, blood, bone marrow Lymph node, lymph, blood, bone marrow Bone marrow

Progressive B lymphocyte maturation

Lymphoid stem cell Maturing B cell many stages

Pre-B acute lympho blastic leukemia B cell lymphoma

Mature B cell Plasma cell

Chronic lympho cytic leukemia Multiple myeloma

   Bimodal age  distribution : young adults ( 20-30 yrs) & elderly (> 50yrs) may occur at any age M > F Lymphadenopathy:   most often cervical region asymmetrical, discrete    painless, non-tender elastic 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 early stage of differentiation : Bi-nucleate cell with a prominent nucleolus. Derived from B cell, at an Reactive background of eosinophils, lymphocytes, plasma cells Fibrous tissue

REED-STERNBERG ( RS ) Cell



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

Hodgkin’s Disease/Lymphoma In the Beginning

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

Stage Definition

I Involvement of a single lymph node region (I) or of a single extralymphatic organ or site (I E ) 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 (II E ) III Involvement of lymph node regions on both sides of the diaphragm (III) which may be accompanied by involvement of the spleen (III S ) or by localized involvement of an extralymphatic organ or site (III E ) or both (III SE) IV Diffuse or disseminated involvement of one or more extra lymphatic organs or tissues with or without associated lymph node involvement B symptoms: fever > 38 º C for three consecutive days, drenching night sweats or unexplained loss 10% or more of weight the preceding 6 months

      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%

   

Stage I

: Involvement of single LN region (I) or extra lymphatic site (IA

E

) 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 (III localized extra lymphatic involvement or involvement of the spleen (II S E ) or without (III) ) or both (IIS E ) Stage IV : marrow) Involvement outside LN areas (Liver, bone A : Absence of ‘B’ symptoms B : B symptoms present

    

Widely disseminated at presentation

Nodal involvement: Painless lymphadenopathy, often cervical region is the most common presentation Hepatosplenomegaly Extranodal :

Intestinal lymphoma

dysphagia);

CNS

( headache, cranial nerve palsies, spinal cord compression) ; Skin, Testis; Thyroid; Lung

Bone marrow

( abdominal pain, anemia, (low grade): Pancytopenia

 

Systemic symptoms

 Sweating, weight loss, itching 

Metabolic complications:

hypercalcemia, renal failure hyperuricemia, Compression syndrome:   Gut obstruction Ascites

     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

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

Indolent Nodular (follicular) Diffuse Aggressive Small cell Large cell

Low grade Proliferation: Low Course: Indolent Symptoms: -ve Treatment: Not curable

Staging

Similar to HD High grade High Rapid, fatal(un-Rx) +ve Potentially Curable

 

Cannot be attributed a single cause

Chromosomal translocations: t (14, 18)  Infection:  Virus:EBV, HTLV,HHV-8, HIV 

Bacteria: H.Pylori - Gastric lymphoma

 Immunology:   Congenital immunodeficiency, Immunocompromised patients - HIV, organ

transplantation

   Immunohistochemistry Immunofluorescence Flow cytometry  Identification of CD’s (cluster determinants)  CD5 = T cell type  CD20 = B cell type

    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 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.

* 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+).

   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.

* 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.