An Epidemiologic Approach to the Lymphomas of African Children and Burkitt's Sarcoma of the Jaws

AN EPIDEMIOLOGIC APPROACH TO THE LYMPHOMAS OF AFRICAN CHILDREN AND BURKITTS SARCOMA OF THEfAWS GILBERT DALLDORF, M.D.; C. A. LINSELL, M.B., B.S., D.C.P.; FRANCES E. BARNHART, M.D.; and RUTH MARTYN, S.R.N.* Five years ago the attention ofphysicians was drawn to a remarkably prevalent malignant tumor of African children. Originally designated simply as a sarcoma ofthejaws, it was later defined as a lymphatic tumor that also might arise elsewhere. Still later, observation of its geographic distribution, defined by altitude, rainfall, and temperature zones, prompted the suggestion that it represents the first instance ofa malignant tumor induced by a mosquito-borne virus. This discussion critically examines the known circumstances and proposes an alternative evaluation of the disease. It is based on information from the Kenya Cancer Registry and on field and laboratory investigations . Kenya seemed exceptionally suitable for such an inquiry because of its varied climatic conditions and substantial accumulation of information concerning the prevalence ofmosquito-borne diseases. For reasons that will become clear later on, we have chosen to refer to the tumor as a lymphoma, or lymphosarcoma, being restrained by our observations from assigning a specific name to it. In East Africa the tumor is frequently called "a Burkitt" in commemoration ofBurkitt's pioneer observation , and Wright has formally urged that this term be adopted [i]. A disadvantage of such eponymy is that a uniqueness is implied that we are not disposed to accept. "Multifocal lymphoma," suggested by Gluckman [2], or "multicentric," used by Trowell [3], would be better, being descriptive ofa prominent characteristic. They also have the virtue of not implying too much and yet distinguishing the disease in question. * Walker Laboratory, Sloan-Kettering Institute, New York, and Medical Research Laboratory, Nairobi, Kenya. 435 I. Historical Background The early reports of the tumor in Uganda made by Burkitt [4] and Davies and Davies [5] identified the main features ofthe disease as its commonness , apparently limited geographic distribution, striking and specific age distribution, and characteristic and unusual anatomical pattern particularly affecting the jaw bones. It was recognized that the disease was not new to Uganda because convincing reports were found in the notes of Sir Albert Cook, a missionary doctor working there at the beginning ofthis century. O'Conor and Davies [6] described the histology ofthe tumor as a poorly differentiated lymphoma in which the lymphocytic cells were interspersed with numerous histiocytes giving a "water-pot" or "starry-sky" effect. O'Conor [7] suggested that although this form was the more usual, there were variations ranging from a stem-cell type to a tumor in which histiocytic cells predominated. Burkitt mapped the distribution ofthe tumor within Africa, using published reports, inquiries from doctors working in tropical Africa, and personal safaris. Haddow [8, 9] noted that those areas ofAfrica where most of the "wet tropics" groups of mosquitos did not thrive were associated with low incidence of the disease. These were defined as areas over 5,000 feet, or where seasonal mean temperatures do not fall below 6o° F., or the annual rainfall was less than 20 inches. This was translated into a positive association between insect vectors and areas ofhigh incidence, and an insect-borne viral etiological agent was postulated for what was thought to be a unique human tumor. Search for a specific virus was energetically commenced. Considerable resources have been brought to bear on the problem, but so far no specific viral agent has been reported. Obviously, a number offactors make this hypothesis ofa new clinical and pathological entity attractive; but once uniqueness of a disease is accepted, inevitably study ofits etiology is directed along narrow channels. Early descriptions stressed that leukemia was rarely or never seen. The low incidence of leukemia in the areas where the lymphoma was most common was noted by O'Conor and Davies [6], and the possible significance ofthe reciprocal relationship between the lymphomas and leukemia was emphasized [10]. Detailed investigation of cases of lymphoma in Kenya has since shown that terminal leukemia is not so uncommon as had been suggested [11]. It was originally postulated that the disease is confined to children below 436 Gilbert Dalldorfet al. · Lymphomas ofAfrican Children Perspectives in Biology and...