We searched for articles in English on Medline and Embase with the search terms “Burkitt lymphoma” and “Burkitt's lymphoma”, together with the terms “paediatric”, “pediatric”, “children”, “adult”, “sporadic”, “epidemiology”, “co factor”, “HIV”, “malaria”, “EBV”, “pathology”, “immunology”, “treatment”, and “outcome”. We also searched the reference lists of articles identified by this strategy. We did not limit ourselves by date so as to provide historical context.
SeminarBurkitt's lymphoma
Section snippets
Introduction and history
Burkitt's lymphoma has had an important role in the understanding of tumorigenesis. It was the first human tumour to be associated with a virus,1 one of the first tumours shown to have a chromosomal translocation that activates an oncogene,2, 3 and the first lymphoma reported to be associated with HIV infection.4 Burkitt's lymphoma is the fastest growing human tumour, with a cell doubling time of 24–48 h, and was the first childhood tumour to respond to chemotherapy alone.5 It is the most
Classification
The WHO classification of Burkitt's lymphoma describes three clinical variants: endemic, sporadic (the predominant type found in non-malarial areas), and immunodeficiency-related.20 These types are similar in morphology, immunophenotype, and genetic features. The endemic variant is associated with malaria endemicity and EBV is found in almost all cases. The sporadic type occurs mainly throughout the rest of the world (predominantly North America and Europe), with no special climatic or
Epidemiology
The distribution of endemic Burkitt's lymphoma across Africa and Papua New Guinea corresponds to areas of holoendemic malaria and the early acquisition of EBV.13, 26, 27, 28, 29, 30, 31, 32 The annual incidence has been estimated at 40–50 per million children younger than 18 years.33 In these high-risk areas endemic Burkitt's lymphoma comprises about half of all childhood cancer diagnoses and up to 90% of lymphoma diagnoses. Incidence peaks at age 6 years and the disease is twice as common in
Epstein-Barr virus
Several observations suggest a direct causative role for EBV in endemic Burkitt's lymphoma. For example, EBV is consistently present in these tumours;37 infection of malignant B cells precedes tumorigenesis;38 EBV induces immortalisation of B cells in culture; and very high EBV antibody titres are recorded in children before development of the disease.39 However, the underlying mechanism linking EBV infection of B cells to the emergence of malignancy remains undiscovered.
Although EBV encodes
Clinical presentation
The most common site of presentation in sporadic Burkitt's lymphoma is the abdomen (60–80%).21 Presenting symptoms include abdominal pain (25% of patients have ileocaecal disease—either a right lower quadrant mass or pain from intussusception), distension, nausea and vomiting, and gastrointestinal bleeding.86, 87 The next most common site is the head and neck, including lymphadenopathy and involvement of the nasal or oropharynx, tonsils, or sinuses. The jaw is infrequently implicated. Bone
Histopathology and immunocytochemistry
Burkitt's lymphoma is a highly aggressive B-cell non-Hodgkin lymphoma characterised by monomorphic medium-sized cells with a very high proliferation rate (figure 4). The cells are intermediate in size and contain coarse chromatin and prominent basophilic nucleoli. Some plasmacytoid and atypical variants show more nuclear pleiomorphism. In tissue sections, typically the cells seem to be moulded and the cytoplasm is deeply basophilic with squared-off cytoplasmic margins. The proliferation index
Cytogenetics and molecular studies
The translocation t(8;14)(q24;q32) is the hallmark of Burkitt's lymphoma and occurs in 70–80% of patients. The variant translocations, t(2;8)(p12;q24) and t(8;22)(q24;q11), occur in 10–15% of patients.93, 94, 95 The molecular consequence of the three translocations is deregulated expression of the MYC oncogene, which has an essential role in cell cycle control. Deregulated expression arises as a result of juxtaposition of MYC to the enhancer elements of one of the immunoglobulin genes: the
High-income countries
Diagnosis of Burkitt's lymphoma should be confirmed by microscopy and immunocytological analysis (figure 5). The recommended approach is to remove and examine the most accessible disease-containing tissue. This sample could be a superficial lymph node or malignant pleural fluid. Excision biopsy of a lymph node is preferable to fine-needle aspiration, which does not provide sufficient tissue for all the investigations required. In some cases a laparotomy or laparoscopy is necessary to obtain
Prognostic markers
Therapy is guided partly by clinical and histopathological staging with biological features beginning to inform therapeutic strategies. Clinically, prognosis is determined by staging, which includes extent of disease.106 The St Jude/Murphy classification for Burkitt's lymphoma is the most common staging system used (panel).107 Cytogenetic analysis is important in diagnosis to identify MYC deregulation and the presence of additional cytogenetic abnormalities, some of which have been shown to
High-income countries
Treatment of Burkitt's lymphoma in most centres is guided by the FAB LMB study (cooperative study between the Children's Cancer Group, the Société Française d'Oncologie Pédiatrique, and the UK Children's Cancer Study Group)86, 87 or Berlin–Frankfurt–Münster protocols. The former consists of initial cytoreduction with cyclophosphamide, prednisolone, and vincristine, followed by more intensive chemotherapy in varying combinations. The risk of pronounced tumour lysis is high in the first few days
Outcome
The outcome for sporadic Burkitt's lymphoma in high-income countries is excellent with an overall cure rate of roughly 90%. In most studies all B-cell non-Hodgkin lymphomas and B-cell leukaemias are treated similarly. Separate subanalyses of children with Burkitt's lymphoma are not always published. Children with resected stage I and II disease have event-free survival and overall survival above 98%.17 Those with stage III and IV disease do less well if lactose dehydrogenase concentrations are
Adult Burkitt's lymphoma
Burkitt's lymphoma in adults is uncommon with an annual incidence of about 1200 patients in the USA. The disease occurs at any age, although 59% of patients are older than 40 years. As in children, in adults the disease can be associated with HIV infection or other immunodeficiencies.126 Outcome in adult patients has been poor, but is improving. No randomised therapeutic trials have been done for adult Burkitt's lymphoma.
Adults present with rapidly developing disease, commonly in the abdomen,
Future
In low-income countries better diagnostic testing is needed. When only morphology is available, tumours are probably incorrectly classified as Burkitt's lymphoma. Additionally, a high standard of supportive care and medical infrastructure is necessary to deliver the most effective therapy. New, effective, and inexpensive therapies are needed for low-income countries. One possibility is to use compounds with histone deacetylase inhibitor activity as adjuvant therapy.135 These agents stimulate
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