Lymphomas are malignant proliferation of the lymphoid tissue2 broad classification: Hodgkin’s d’se and Non-Hodgkin’s lymphoma
Divided into 2 general prognostic groups: Indolent lymphomas-relatively good prognosis Aggressive lymphomas NHL may also be characterized as low, intermediate & high grade. Low & intermediate predominate in adults 90% of childhood NHL are high grade.
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
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
Noknown 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 abnormalities : 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; and A cytogenetic error emerges & endows the cells with survival advantage4 Oncogenes: These are genes which cause cancer4 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
o Chemistries: RFT-Creatinine, BUN Electrolytes-K, PO4-, Ca, Na LFTo Lactate dehydrogenase (LDH):- elevated (poor prognostic factors), correlation with increased tumor burdeno HIV serology
o Imaging studies: Abdominal US CXR CT scan Echocardiographyo Cytogenetic studies
o Procedures: Biopsy for histology LP for CSF cytology BMA 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 diagnosis Debulking-reduction of tumor volume Laminectomy to relieve spinal cord compression Insertion of omaya reservoir for intraventricular therapy.
Chemotherapy : Isthe Rx of choice BL is highly sensitive to chemotherapy. Pre-chemotherapy medications: Fluid preload-orally or IV to ensure high urinary output Allopurinol 4-5 days before and after administration of drug Correction of any metabolic imbalance or haematologic abnormality Dexamethasone
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