Presenter: Dr Opiro Keneth,

Date: 6th July 2012

Introduction Definition Epidemiology Aetiology Clinical Features Investigations Staging Treatment Prognosis

Lymphomas are malignant proliferation of the lymphoid tissue

2 broad classification: Hodgkin’s d’se and Non-Hodgkin’s lymphoma

Divided into 2 general prognostic groups:Indolent lymphomas-relatively good prognosisAggressive lymphomas

NHL may also be characterized as low, intermediate & high grade.

Low & intermediate predominate in adults

90% of childhood NHL are high grade.

High grade NHLs comprise of 3 histological subtypes:Small non-cleaved cells e.g Burkit,s LymphomaLymphoblasticLarge cell lymphoma

Defn: It’s a NHL of the high grade type Small non-cleaved cell lymphoma, exclusively of

B-cell origin

Burkitt lymphoma is named after Denis Parsons Burkitt, 1958,who mapped its peculiar geographic distribution across Africa

2 epidemiological types:Endemic BL - African typeNon-endemic - Sporadic BL*HIV associated BL*

Endemic BL (African type): Distributed btn 15oN & 15oS of the equator

(lymphoma belt) The area of highest risk for BL in Africa

(incidence 5 – 15 per 100,000 children) Within this belt, there are pockets where the

tumor is extremely rare-in high altitude areas (no known reason)

Restricted to those areas with annual rainfall >50cm & an average temp in the coolest month of over 15.6oC

BL commonly affects children Peak age btn 4-7yrs (6-7yr) Uncommon below 1yr of age, and <1% of children

get it below 2yrs. Less than 10% of patients are diagnosed after the

age of 15yrs M:F =2:1

No known cause1 EBV: Epstein-Barr virus, a member of the family Herpesviridae, which can be isolated from tumor

cells in culture,there is a strong association btn endemic BL and EBV. Found in 95% of cases.

2 Malaria: chronic severe falciparum malaria infn lead to intense host response with proliferation of the lymphoreticucar system, particularly of the B-lymphocytes.

3 Chromosomal abnormalit ies:t(8;14)-80%, t(8;22)-15%, t(2;8)-5%, this leads to

activation of c-Myc oncogene

In 1979, George Klein postulated a three-stage pathogenic step required for the dev’t of endemic BL:EBV transforms B cells & immortalizes them;An env’tal factor, e.g holoendemic malaria promotes

polyclonal proliferation of B cells; andA cytogenetic error emerges & endows the cells with

survival advantage

4 Oncogenes: These are genes which cause cancer

4 Hiv Infection: In HIV associated burkitts lymphoma

Endemic BL Presents with jaw swelling in 75% Maxillae are affected more frequently than the

mandibles Maxillary tumor often involves the orbit as well The first clinical evidence is often loosening of

teeth Non-jaw tumors present mainly as abdominal

mass in ~60%

Virtually any abdominal organ can be involved-liver, kidneys, ovaries, suprarenal & retroperitineal LNs, may have Ascites

CNS involvement- 3rd most common mode of presentation

Seen in ~30% of pts Often presents as cranial nerve palsy with or

without malignant spinal fluid pleocytosis Peripheral node involvement is rare in endemic

cases.

Pleura, Endocrine glands, Testis, skin may be involved Bone marrow only 7-8% even after multiple relapses Parotid glands

In non-endemic areas; The most common site of presentation is with

abdominal d’se in 90% (often ovary & ileocaecal) Peripheral node d’se –in 20% of pts Jaw involvement -10% CNS involvement-5% *jaw tumor most common in young children while

abdominal d’se increases in frequency with age*

Jaw: Disfigurement, loosening and loss of teeth, halitosis, difficulty feeding and speech

Abdomen: Masses, distention, pain, constipation, diarrhea, difficulty breathing, obstructive uropathy, IO, and GI perforation.

Orbit: Proptosis, altered vision, disfigurement CNS/PNS: LOC, cranial nerve palsies, sphincter

abnormalities (retention or incontinence), paraplegia, etc.

Fever, loss of appetite, loss of weight, frequent morbidity

Investigations: Aims:

DiagnosticStaging & pre-chemotherapyFollow up

o CBC: Neutrophil (ANC) >1000/ulHb >7g/dlPLT 150,000/ul

o Chemistries: RFT-Creatinine, BUNElectrolytes-K, PO4-, Ca, Na LFT

o Lactate dehydrogenase (LDH):- elevated (poor prognostic factors), correlation with increased tumor burden

o HIV serology

o Imaging studies:Abdominal USCXRCT scanEchocardiography

o Cytogenetic studies

o Procedures:Biopsy for histologyLP for CSF cytologyBMA or biopsy for staging purpose

Histology: The characteristic histological features of BL is the

so-called “Starry Sky” appearance. imparted by scattered macrophages with phagocytes cell debris

Staging of BL: Stage A: Solitary extra-abdominal site Stage AR: Resected intra-abdominal tumor Stage B: Multiple extra-abdominal sites Stage C: Intra-abdominal tumor with or without

facial tumor Stage D: Intra-abdominal tumor with sites other

than facial.

Goal of Rx is cure BL can be treated by surgery & chemotherapy BL is insensitive to radiotherapy. Surgical approaches include:

Biopsy for diagnosisDebulking-reduction of tumor volumeLaminectomy to relieve spinal cord compressionInsertion of omaya reservoir for intraventricular therapy.

Chemotherapy: Is the Rx of choice BL is highly sensitive to chemotherapy. Pre-chemotherapy medications:

Fluid preload-orally or IV to ensure high urinary outputAllopurinol 4-5 days before and after administration of

drugCorrection of any metabolic imbalance or haematologic

abnormalityDexamethasone

Divided into high risk and low risk Patient

Low Risk : Extra-abdominal tumor <10 cm

High Risk : All, other than above, eg CNS, intra-abdominal, extra-abdominal tumour >10cm,etc

Combination chemotherapy is used: 1st line (COM):

• Cyclophosphamide• Oncovin (Vincristine)• Methotrexate (MTX) • + IT MTX + cytocine arabinoside:

Prophylactic x 3 courses(for low risk)Therapeutic in CNS d’se x all 6 courses(for high risk)

Course repeated every 2 weeks x 6 courses.

90% curable especially early disease Tumour burden (total tumor volume)◦ clinical stage◦ serum LDH

Tumor lysis syndrome >90% tumor reduction by surgery Early relapse (3 month), CR 50% vs. late

relapse, CR 90%. CNS relapse in African Burkitt’s, is not a bad

prognostic factor

Radiotherapy,BL is a radio-sensitive tumour but b’se of it’s rapid

growth, radiotherapy is ineffectiveTumour regrows btn @ day’s therapyProphylactic craniospinal irradiation achieved no

results in preventing or delaying CNS relapse

ANY QUESTIONS?