Burkitt lymphoma is an unusual tumour in Western countries, but may occur in association with HIV or other immunodeficiency syndromes.
Burkitt lymphoma has three clinical variants described by the WHO:
- Endemic Burkitt lymphoma occurs in equatorial countries with a similar distribution to malaria infections. It is a common childhood malignancy in Papua New Guinea, and is the most common childhood malignancy in equatorial Africa
- Sporadic Burkitt lymphoma is seen throughout the world, usually in childhood or early adulthood. It is an unusual form of lymphoma, making up less than 2% of diagnoses in Western countries. About 30-50% of childhood lymphomas are Burkitt lymphoma.
- Immunodeficiency-associated Burkitt Lymphoma is an evolving disease as HIV infection becomes more widespread. It can also be seen in people who have other causes of immunosuppression (such as organ transplant)
Endemic Burkitt lymphoma is usually seen in areas with a high rate of malaria infection. These tumours commonly incorporate the Epstein-Barr Virus (EBV) genome, and it is thought that malaria may allow EBV infection to progress to Burkitt lymphoma.
In other types of Burkitt lymphoma, EBV is less prevelant in tumour cells (30-40%) and other aetiologies are implicated. HIV infection is strongly linked to Burkitt lymphoma, moreso than other causes of immmnodeficiency. The exact mechanism by which HIV causes Burkitt lymphoma is not well understood although it seems likely that it has an additional role over and above the immunodeficiency.
The most commonly seen genetic abnormality is translocation of MYC (chromosome 8) to the location of immunoglobulin genes. The most commonly observed translocation is t(8;14), with the immunoglobulin heavy chain region. Other translocations - such as t(8;22) or t(8,2) are sometimes seen. Other genetic abnormalities are also common.
MYC is a potent oncogene that promotes cell survival, progression through the cell cycle and a host of other factors.
Most commonly the disease presents rapidly, with large mass lesions throughout the body. Untreated, the disease is rapidly fatal within several weeks.
Symptoms and Signs
Patients usually complain of a rapidly growing mass. The exact symptoms and signs depend on the location of the mass, which may occur in any body tissue but is more commonly extra-lymphatic. The central nervous system is commonly involved. Facial bones are the site of presentation in about 50% of endemic Burkitt lymphoma, although this is rare in sporadic types. The ovaries, kidneys and breasts are commonly involved, with the disease often presenting during puberty or pregnancy.
Burkitt lymphoma may occasionally present as a leukaemia with circulating malignant cells on full blood examination.
CT imaging usually shows mass lesions in solid organs or diffuse thickening in hollow viscera. PET scanning is usually positive and helps in identifying areas of disease.
Burkitt lymphoma cells have a very high doubling time and patients typically develop symptoms over a few weeks. Presentation is usually with bulky disease or leukaemia symptoms.
Tumours are frequently large and nodular. Areas of necrosis and haemorrhage may be visible. There is destruction of neighbouring normal tissue, including bone.
H&E staining demonstrates a diffuse pattern of medium sized cells, with a high nuclear-cytoplasmic ratio, hyperchromatic nucleus, and a basophilic cytoplasm. There is a very high number of mitoses seen, as well as numerous apoptotic bodies. Macrophages, with pale cytoplasm, can be seen within the horde of lymphoma cells. This results in the classical histological appearance of a 'starry sky' (the macrophages are the stars).
Immunohistochemical stains can be helpful in differentiating Burkitt lymphoma from other types:
- B cell markers are usually positive (CD19, CD20, CD22)
- Ki-67 is highly positive (should be 100%)
- BCL2 is usually negative or weakly positive
- Cell membranes stain heavily for IgM
The Ann Arbor staging system is currently used for lymphoma. It is 'not considered practical' for a TNM staging system for lymphoma to be developed.
|I||Involvement of one lymph node site|
|IE||Involvement of a single extra-lymphatic site|
|II||Involvement of two or more lymph node sites, on one side of the diaphragm|
|IIE||Involvement of a single extra-lymphatic site and one or more lymph node groups, on one side of the diaphragm|
|III||Involvement of lymph nodes on both sides of the diaphragm|
|IIIE||Involvement of a single extra-lymphatic site, with nodes on both sides of the diaphragm|
|IIIS||Involvement of the spleen with nodes on both sides of the diaphragm|
|IIIE+S||Involvement of the spleen, a single extra-lymphatic site, with nodes on both sides of the diaphragm|
Although it is highly aggressive, Burkitt lymphoma is also relatively responsive to treatment.
- Early stage disease in childhood carries a cure rate of over 90%
- Most cases in Western countries have a cure rate of about 70%
- In Africa the disease is rapidly fatal due to a lack of funding for modern medical care