Burkitt's lymphoma

Burkitt's lymphoma (or "Burkitt's tumor", Burkitt lymphoma or "malignant lymphoma, Burkitt's type") is a cancer of the lymphatic system (in particular, B lymphocytes). It is named after Denis Parsons Burkitt, a surgeon who first described the disease in 1956 while working in equatorial Africa.^[1][2]

Classification

Currently Burkitt's lymphoma can be divided into three main clinical variants: the endemic, the sporadic and the immunodeficiency-associated variants. Burkitt's lymphoma is usually associated with over 90% of AIDS cases.

• The endemic variant occurs in equatorial Africa. It is the most common malignancy of children in this area. Children affected with the disease often also had chronic malaria, which is believed to have reduced resistance to Epstein-Barr virus (EBV), allowing it to take hold. The disease characteristically involves the jaw or other facial bone, distal ileum, cecum, ovaries, kidney or the breast.

• The sporadic type of Burkitt lymphoma (also known as "non-African") is another form of non-Hodgkin lymphoma found outside of Africa. The tumor cells have a similar appearance to the cancer cells of classical African or endemic Burkitt lymphoma. Again it is believed that impaired immunity provides an opening for development of the Epstein-Barr virus. Non-Hodgkin lymphoma, which includes Burkitt's, accounts for 30-50% of childhood lymphoma. The jaw is less commonly involved, compared to the endemic variant. The ileo-cecal region is the common site of involvement.

• Immunodeficiency-associated Burkitt lymphoma is usually associated with HIV infection^[3] or occurs in the setting of post-transplant patients who are taking immunosuppressive drugs. Burkitt lymphoma can be one of the diseases associated with the initial manifestation of AIDS.

By morphology (i.e. microscopic appearance) or immunophenotype, it is almost impossible to differentiate these three clinical variants. Immunodeficiency-associated Burkitt lymphoma may demonstrate more plasmacytic appearance or more pleomorphism, but these features are not specific.

Epidemiology

Of all cancers involving the same class of blood cell, 2% of cases are Burkitt's lymphoma.^[4]

Malignant B cell characteristics

Normal B cells possess rearranged immunoglobulin heavy and light chain genes and each isolated B-cell possesses a unique IgH gene rearrangement. Since Burkitt lymphoma and other B-cell lymphomas are a clonal proliferative process, all tumor cells from one patient are supposed to possess identical IgH genes. When the DNA of tumor cells is analyzed using electrophoresis, a clonal band can be demonstrated, since identical IgH genes will move to the same position. On the contrary, when a normal or reactive lymph node is analyzed using the same technique, a smear rather than a distinct band will be seen. This technique is useful since sometimes benign reactive processes (e.g. infectious mononucleosis) and malignant lymphoma can be difficult to distinguish.

Microscopy

The tumor consists of sheets of a monotonous (i.e. similar in size and morphology) population of medium size lymphoid cells with high proliferative activity and apoptotic activity. The "starry sky" appearance seen^[5] under low power is due to scattered tingible body-laden macrophages (macrophages containing dead body of apoptotic tumor cells). The old descriptive term of "small non-cleaved cell" is misleading. The tumor cells are mostly medium in size (i.e. tumor nuclei size similar to that of histiocytes or endothelial cells). "Small non-cleaved cells" are compared to "large non-cleaved cells" of normal germinal center lymphocytes. Tumor cells possess small amount of basophilic cytoplasm. The cellular outline usually appears squared off.

Immunohistochemistry

The tumor cells in Burkitt lymphoma generally strongly express markers of B cell differentiation (CD20, CD22, CD19) as well as CD10, and BCL6. The tumour cells are generally negative for BCL2 and TdT. The high mitotic activity of Burkitt lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67. ^[6]

Genetics

Almost by definition, Burkitt's lymphoma is associated with a chromosomal translocation of the c-myc gene. This gene is found at 8q24.

• The most common variant is t(8;14)(q24;q32). This involves c-myc and IGH@. A variant of this, a three-way translocation, t(8;14;18), has also been identified.^[7]

• A rare variant is at t(2;8)(p12;q24).^[8] This involves IGK@ and c-myc.

• Another rare variant is t(8;22)(q24;q11).^[8] This involves IGL@ and c-myc.

Treatment

Treatment includes dose-adjusted EPOCH with Rituxan (rituximab).^[9]

Effect of the chemotherapy, as with all cancers, depends on the time of diagnosis. With faster growing cancers, such as Burkitt's, the cancer actually responds faster than with slower growing cancers. This rapid response to chemotherapy can be hazardous to patient, as a phenomenon called "tumor lysis syndrome" could occur. Close monitoring of patient and adequate hydration is essential during the process.

Chemotherapy

• cyclophosphamide
• doxorubicin
• vincristine
• methotrexate
• cytarabine
• ifosfamide
• etoposide
• rituximab^[10]

Other treatments are immunotherapy, bone marrow transplants, surgery to remove the tumor, and radiotherapy.

Prognosis

Treatment with dose-adjusted EPOCH with Rituxan (rituximab) has shown an 8 year survival rate of 91% for low risk, 90% for low-intermediate risk, 67% for high-intermediate risk, and 31% for high risk cases with few of the side effects associated with Burkitt's lymphoma chemotherapy.^[9]

In adults, overall 5-year survival rate is approximately 50%.^[11]

References