Burkitt's Lymphoma

Burkitt's lymphoma was first described by Dennis Burkitt in 1956 in Africa.¹ It is a high-grade B-cell (non-Hodgkin's) lymphoma that is rapidly growing and aggressive. There are three forms:

• Endemic (African) form
• Non-endemic (sporadic) form
• Immunodeficiency associated form

• Most commonly affects children but can occur in adults.²
• Most common in equatorial Africa where incidence may be 100 per million children.² Burkitt's lymphoma is the most common malignancy in children in this area, accounting for 74% of malignancies.^3,4 It peaks at around 5-8 years old.⁴
• Also endemic in Papua New Guinea.⁴
• More common in males.
• The sporadic form is rare in the developed world.

• There is an association with Epstein-Barr virus (EBV). This association is stronger for the endemic form but may still be implicated in about 20% of the sporadic form.²
• It is thought that the affected individual does not mount a sufficient immune response to EBV. This may be due to the presence of other chronic infections such as malaria.¹ Malaria has been recognised as an important cofactor in endemic Burkitt's lymphoma.⁴
• Cells in endemic and sporadic forms are B lymphocytes that have rearranged immunoglobulin genes and contain one of three translocations of the proto-oncogene c-myc. The most common translocation is from the long arm of chromosome 8 to chromosome 14.^2,4
• It has long been proposed that EBV and malaria infection promote this translocation and lead to the development of a malignant clone.⁵ However, Burkitt's lymphoma can occur without the presence of EBV or malaria.⁴
• Arboviral infection (transmitted by insect vectors) and tumour-promoting plant extract derived herbal remedies have also been proposed as cofactors.⁴
• There is also an association with immunodeficiency (including AIDS) in adults.²

Endemic Burkitt's lymphoma

• Most commonly involves the maxilla and/or mandible but abdominal organs may also be involved.²
• Tumour can double in size in 18 hours.³
• Presentation is commonly with:
  • Swelling of the affected jaw/bones
  • Rapidly enlarging, non-tender lymph nodes in the neck/jaw

Sporadic Burkitt's lymphoma

• Usually involves the abdominal organs, most frequently the distal ileum, caecum or mesentery.
• Other abdominal and pelvic organs, glandular tissue such as the thyroid and tonsils, and the facial bones may also be involved.^2,1
• Presentation is commonly with:
  • Abdominal mass/swelling and ascites
  • Abdominal pain
  • Intestinal obstruction

Other presentations

• B symptoms may be present with both forms of Burkitt's lymphoma and include:
  • Fever
  • Weight loss
  • Night sweats
• HIV-related Burkitt's lymphoma tends to present in a similar way to the sporadic disease.⁴
• Rarely Burkitt's lymphoma can undergo leukaemic transformation.

• Biopsy is needed for diagnosis.
• Bone marrow and cerebrospinal fluid examination are usually performed (bone marrow and central nervous system are frequently involved).
• Cytology of any ascitic or pleural fluid should be carried out.
• Chest X-ray, CT and MRI scanning allow staging.

St Jude Modification of Ann Arbor staging:¹

• Stage 1
  • Single extranodal tumour OR localised nodal lymphoma (excluding mediastinal or abdominal lymph nodes)
• Stage 2 - Can be any of:
  • Single extranodal tumour with nearby lymph node involvement
  • Two single extranodal tumours on same side of the diaphragm (± nearby lymph node involvement)
  • Lymphoma originating in the stomach or bowel (± nearby lymph node involvement)
  • Lymphoma involves two or more areas of lymph nodes on same side of diaphragm
• Stage 2R
  • Lymphoma was in the abdominal area and was completely removed by surgery
• Stage 3 - Can be any of:
  • Two single extranodal tumours on opposite sides of the diaphragm
  • Lymphoma originating in the lungs, chest or thymus
  • Lymphoma involving the spinal cord
  • Lymphoma originated in the abdomen and involves a large area
  • Lymphoma involves two or more areas of lymph nodes on opposite sides of diaphragm
• Stage 3A
  • Lymphoma is within the abdominal cavity and is not amenable to surgery
• Stage 3B
  • Lymphoma involves several abdominal organs
• Stage 4
  • Any of the above PLUS, at the time of diagnosis, the central nervous system and/or the bone marrow are involved

Burkitt's lymphoma is a high-grade, rapidly growing lymphoma.

Chemotherapy

• Combination chemotherapy is the treatment of choice, usually involving cyclophosphamide as one of the drugs. Other drugs include vincristine, doxorubicin, methotrexate, cytarabine, ifosfamide and etoposide.¹
• In Africa, single drug chemotherapy using cyclophosphamide has been used in early stage disease with good results.²
• Burkitt's lymphoma is generally very sensitive to chemotherapy.
• Treatment regimes usually include CNS prophylaxis.

Monoclonal antibody treatment

• Rituximab may be given with chemotherapy.¹

Other treatment

• There is a high risk of tumour lysis syndrome. Allopurinol should be started at diagnosis with hydration and alkalinisation and close monitoring of electrolytes. Renal dialysis may be needed.
• Bone marrow transplantation/stem cell infusions may be performed if Burkitt's lymphoma is recurrent or extensive. Regimes may include high dose chemotherapy ± radiotherapy.¹
• Surgery has been used if there is intestinal obstruction or if abdominal tumours are very small and completely resectable.²

• Intestinal obstruction
• Tumour lysis syndrome

• This depends on the stage at diagnosis. If there is localised disease, the survival rate is high (> 90%).²
• Children usually have a better prognosis than adults.
• Prognosis is poor in people with coexistent AIDS as there is usually widespread dissemination at diagnosis.²

Possible future considerations include:³

• Vaccine development for Epstein Barr virus
• Vaccine development for malaria