lymphomas
DESCRIPTION
Lymphomas. WHO Lymphoid Neoplasms. B cell neoplasms T/NK cell neoplasms Hodgkin lymphoma (disease). 2008 Estimated US Cancer Cases*. Men 720,280. Women 679,510. Prostate33% Lung & bronchus13% Colon & rectum10% Urinary bladder6% Melanoma of skin5% - PowerPoint PPT PresentationTRANSCRIPT
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% Breast12% Lung & bronchus11% Colon & rectum 6% Uterine corpus 4% Non-Hodgkin
lymphoma 4% Melanoma of skin 3% Thyroid 3% Ovary 2% Urinary bladder 2% Pancreas22% 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 marrow Bone 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.