Epidemiology

• Most commonly affects children but can occur in adults. Burkitt's and 'Burkitt-like' lymphomas account for fewer than 10% of adult diffuse lymphomas, but account for the majority of childhood B-cell lymphomas.^[3]
• Burkitt's lymphoma is significantly more common in sub-Saharan Africa, where it accounts for approximately one half of childhood cancers.^[2][4] The incidence peaks at around 5-8 years old and is more common in boys.^[2][5]
• The incidence also appears to be higher in South America, North Africa and in the Middle East.^[6] It is also endemic in Papua New Guinea.^[2]
• The sporadic form is rare in the developed world.
• There is an association with Epstein-Barr virus (EBV) and the sporadic and endemic forms of Burkitt's lymphoma. This association is stronger for the endemic form but may still be implicated in about 20% of the sporadic form.
• Malaria has been recognised as an important cofactor in endemic Burkitt's lymphoma.^[2]
• Arboviral infection (transmitted by insect vectors) and tumour-promoting plant extract-derived herbal remedies have also been proposed as cofactors.^[2]

Presentation

Endemic Burkitt's lymphoma

• Most commonly involves the maxilla and/or mandible but abdominal organs may also be involved.
• A tumour can double in size in 18 hours.^[4]
• 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.^[7]
• 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.^[2]

Investigations

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

Staging

St Jude Modification of Ann Arbor staging:^[7]

• 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 the 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 the same side of the 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 the 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 CNS and/or the bone marrow are involved.

Management

Burkitt's lymphoma is a fast-growing tumour but also very sensitive to chemotherapy. However, sporadic and immunodeficiency-associated Burkitt's lymphoma can be less sensitive to chemotherapy than the the endemic variant.^[5]

Different regimens have been used with varied success rates.^[8] The development of brief but very intensive chemotherapy has led to a very high cure rate in children with Burkitt's lymphoma. The use of these regimens in adults, often in combination with the monoclonal antibody rituximab, can also be very effective.^[9]

Chemotherapy

• Combination chemotherapy is the treatment of choice; drugs used include cyclophosphamide, vincristine, doxorubicin, methotrexate, ifosfamide, cytarabine and etoposide.^[7]
• Treatment regimes usually include CNS prophylaxis with intrathecal chemotherapy.
• Non-intensive chemotherapy with cyclophosphamide and methotrexate may be an alternative to intensive chemotherapy for the management of the stage I-III endemic Burkitt's lymphoma in developing countries.^[10]

Monoclonal antibody treatment

• Rituximab may be given with chemotherapy.^[7]

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 or stem cell transplants may be performed if Burkitt's lymphoma is recurrent or extensive. Regimes may include high-dose chemotherapy ± radiotherapy.^[7]
• Surgery has been used if there is intestinal obstruction or if abdominal tumours are very small and completely resectable.

Complications

• Intestinal obstruction
• Tumour lysis syndrome

Prognosis

• This depends on the stage at diagnosis. If there is localised disease, the survival rate is high (>90%).
• The outcome of adult patients with Burkitt's lymphoma, especially those over 40 years of age, is generally worse than for children and adolescents.^[11] However, some patients aged over 40 years now have a good prognosis with modern treatment regimes.^[12]
• Prognosis is poor in people with co-existent AIDS as there is usually widespread dissemination at diagnosis.
• Rarely, Burkitt's lymphoma can undergo leukaemic transformation.^[5]

Prevention

Possible future considerations include:^[4]

• Vaccine development for Epstein Barr virus (EBV).
• Vaccine development for malaria.