linical picture, Burkitt’s lymphoma

This very malignant tumour originating from B-lymphocytes generally presents with swelling of the jaw and mouth ulcerations (African endemic form), but may be located primarily in the abdomen or the brain (cosmopolitan, non-endemic form). There are no blast cells in the peripheral blood, but in a closely related form there is a leukaemic phase (ALL-type [acute lymphoblastic lymphoma]). Histologically a monotonously uniform picture can be recognised, consisting of small cells with round to oval nuclei containing two or more prominent nucleoli. The basophilic cytoplasm may contain clear fat vacuoles (Oil Red O positive). There are many mitoses. The histological picture is sometimes described as a starry sky. The stars are macrophages. Metastasis occurs chiefly to the brain and bone marrow. The disease occurs almost exclusively in children. Infection with the Epstein-Barr virus (cf. mononucleosis) probably plays an important part in the endemic form of Burkitt’s lymphoma. Epstein-Barr viral DNA is found in more than 90% of African Burkitt’s lymphomas. Only one protein, EBNA-1, [Epstein-Barr nuclear antigen-1] is expressed. Repeated malaria attacks may have a mitogenic effect on infected B-lymphocytes increasing the risk of degeneration. The reciprocal chromosomal translocation 8q24  14q32 is considered as typical. A cellular proto-oncogene (c-myc) of chromosome 8 is hereby translocated to chromosome 14, next to the genes coding for the heavy chains of immunoglobulins. The proto-oncogene can also be translocated either next to the kappa genes (κ) coding for the light chains on chromosome 2 or the lambda genes (λ) for the light chains on chromosome 22. This repositioning to chromosome 2, 14 or 22 disturbs the control of the c-myc gene and gives rise to malignant growth behaviour. [Translocations of the gene bcl-2 from its normal place on chromosome 18 to a place next to the genes for the heavy chains on chromosome 14 is also sometimes found in the related follicular lymphoma. Normally the gene product bcl-2 prevents cellular apoptosis (programmed cell death]). Nevertheless the pathogenesis of Burkitt’s lymphoma is not yet completely clear.

The tumour can be treated with cytostatic drugs. Good results with IV cyclophosphamide (Endoxan®) among other drugs, are not unusual (the target dose 1-1.5 gram/m² IV every 3-4 weeks with 2 doses in remission). The alkylating cyclophosphamide should not be confused with the immunosuppressive cyclosporin! During treatment gout and haemorrhagic cystitis sometimes occur as complications. Allopurinol protects from the risk of hyperuricaemia during tumour lysis. If available, methotrexate (15 mg/m² P.O. for 3 days) and vincristine (1.5 mg/m² IV per week) may be given in addition. Citrovorum factor (leukovorin) is not necessary during brief administration of methotrexate. Combinations of several cytostatic drugs are sometimes used, e.g. CHOP or hyper-CVAD, cytarabine, L-asparaginase. CHOP consists of: cyclophosphamide 750 mg/m² IV day 1, doxorubicin 50 mg/m² IV day 1, vincristine 1.5 mg/m² mg IV day 1 and prednisolone 100 mg/m² per day for 5 days. Neurotoxicity such as polyneuritis during use of Vinca alkaloids is an inherent danger. Bone marrow suppression should be carefully monitored. Doxorubicin is cardiotoxic. Surgical debulking is sometimes carried out. Monoclonal antibodies (Mabthera®, Rituxan®) aimed at the B-cell specific CD-20 antigen which is expressed by 95% of all B-cell lymphomas, are almost never available but can be used in low-grade lymphomas. In the differential diagnosis, the possibility of a deep mycosis (e.g. rhinophycomycosis, mucormycosis) or a chronic abscess of the tooth, jaw or sinuses should be borne in mind.

Category: Medicine Notes