Burkitt lymphoma in Uganda: 50 years of ongoing discovery

W hile working in Uganda, a physician by the name of Denison Parson Burkitt first described the tumor that now carries his name. In 1957, Dr. Burkitt, along with his colleagues, examined a child with what appeared to be swelling along the jaw. After observing a second child with the same clinical presentation, his curiosity prompted him to study hospital records for similar cases. He found that these tumors affecting the mandible and maxilla were not unusual [1]. He began to record cases that presented to hospital as well as contacting colleagues throughout sub-Saharan Africa to determine whether or not this characteristic tumor had been observed elsewhere. Colleagues in Kenya, (then) Tanganyika, Nigeria, (then) Belgian Congo, and (then) Rhodesia all confirmed seeing cases similar to the ones he was observing in Uganda. He published these findings in 1958 in the British Journal of Surgery in an article titled ‘‘A sarcoma involving the jaws of African children’’ [2]. In this issue of Pediatric Blood & Cancer, Orem et al. [3] continue Dr. Burkitt’s work by compiling medical records, summarizing their observations, and trying to improve the prognosis of children diagnosed with cancer in Uganda today. Estimates predict that by 2020, the number of new cancer cases will increase by 15 million, with the burden of cancer morbidity and mortality carried by developing countries. By this date, the total number of new cases in developed nations is expected to increase by 29% while the total number of cases in developing countries is expected to increase by 73% [4]. Currently only 5% of all global cancer resources are spent in developing countries [5]. In conjunction with the increase in cases, mortality is estimated to be approximately fivefold greater in economically disadvantaged countries when compared to industrialized nations [6], even though one third of these cancers are preventable and another third are treatable if detected early. Unfortunately, approximately 75% of cancer patients in developing countries are in advanced stages of the disease by the time they reach a health care facility with the capacity to diagnose and treat cancer [7]. In order to increase cancer awareness in Africa, the World Health Organization (WHO) has delineated overarching priorities. This strategy involves cancer prevention, registries, early diagnosis and treatment, and palliative care; including provisions that ‘‘responses should be culturally appropriate, economically feasible, and evidence-based’’ [8]. This renewed global interest parallels increased cancer research conducted in Africa within the context of public health priorities faced by these communities. This is especially true due to the prevalence of AIDS-related lymphomas [9] that did not exist during Denis Burkitt’s tenure in Uganda. For childhood cancer in Africa, the study by Orem et al. [3] was able to analyze an impressive number of medical records that were available from 1994 to 2004 to determine the impact of HIV infection on the response to cytotoxic treatment and prognosis of children with Burkitt lymphoma. This is the first report of its kind and offers clinicians a slight reprieve by demonstrating that children diagnosed with Burkitt lymphoma had similar response rates to chemotherapy irrespective of their HIV status. While the study found that the overall survival in children with HIV was poorer than HIV-seronegative children, these patients were seen prior to the wide-spread rollout of anti-retroviral therapy in Uganda. Unlike in adults, where Burkitt lymphoma is an AIDS-defining malignancy, HIV does not appear to be a risk factor for pediatric Burkitt lymphoma [10]. However, the authors raise the issue that concomitant HIV infection may influence clinical presentation (i.e., tumor site) or rate of tumor progression. Their finding that HIVseropositive children present more commonly with lymphadenopathy was also reported in a study conducted in Malawi [11]. Most HIV-infected children arrived at hospital in advanced stage of disease, which also contributed to poor prognosis. Unlike Kaposi sarcomas, there has not been a dramatic decrease in the incidence of HIV-associated non-Hodgkin lymphomas since the introduction of highly active antiretroviral therapy [12]. These clinicalepidemiologic observations emphasize differences in risk factors and tumorigenesis of AID-defining malignancies and reinforce the need to understand etiologic mechanisms leading to a diagnosis of Burkitt lymphoma. The role of another viral co-infection was described for Burkitt lymphoma in 1964 after the isolation of the Epstein–Barr Virus (EBV) by Drs. Epstein, Barr and Achong from a Ugandan patient tumor sample [13]. After the discovery of EBV as a risk factor, a geographic association with high malaria transmission was mapped for endemic Burkitt lymphoma in Africa [14]. This led to the hypothesis that malaria suppressed immune surveillance to EBV and thereby allowed tumorigenesis. However, malaria is not ‘‘immunosuppressive’’ but rather ‘‘immune-modulating’’ concluded by the fact that children with malaria are not at increased risk for opportunistic infections such as those observed in people