Table 2. Major Histopathological Categories of Non-Hodgkin Lymphoma in Children and Adolescentsa continued...
Burkitt and Burkitt-like lymphoma/leukemia
Burkitt and Burkitt-like lymphoma/leukemia in the United States accounts for about 30% of childhood NHL and exhibits consistent, aggressive clinical behavior.[2,3,7] The overall incidence of Burkitt lymphoma is 2.5 cases per million person-years and is higher among boys than girls (3.9 vs. 1.1).[2,8] The most common primary sites of disease are the abdomen and the lymph nodes, especially of the head and neck region.[3,8] Other sites of involvement include testes, bone, skin, bone marrow, and central nervous system (CNS).
The malignant cells show a mature B-cell phenotype and are negative for the enzyme terminal deoxynucleotidyl transferase (TdT). These malignant cells usually express surface immunoglobulin, most bearing surface immunoglobulin M with either kappa or lambda light chains. A variety of additional B-cell markers (e.g., CD20, CD22) are usually present, and almost all childhood Burkitt/Burkitt-like lymphoma/leukemia express CALLA (CD10). Burkitt lymphoma/leukemia expresses a characteristic chromosomal translocation, usually t(8;14) and more rarely t(8;22) or t(2;8). Each of these translocations juxtaposes the c-myc oncogene and immunoglobulin locus regulatory elements, resulting in the inappropriate expression of c-myc, a gene involved in cellular proliferation.
The distinction between Burkitt and Burkitt-like lymphoma/leukemia is controversial. Burkitt lymphoma consists of uniform, small, noncleaved cells, whereas Burkitt-like lymphoma is a highly disputed diagnosis among pathologists because of features that are consistent with diffuse large B-cell lymphoma. Cytogenetic evidence of c-myc rearrangement is the gold standard for diagnosis of Burkitt lymphoma. For cases in which cytogenetic analysis is not available, the WHO has recommended that the Burkitt-like diagnosis be reserved for lymphoma resembling Burkitt lymphoma or with more pleomorphism, large cells, and a proliferation fraction (i.e., Ki-67[+] of ≥99%). Studies have demonstrated that the vast majority of Burkitt-like or "atypical Burkitt" lymphomas have a gene expression signature similar to Burkitt lymphoma. Additionally, as many as 30% of pediatric diffuse large B-cell lymphoma cases will have a gene signature similar to Burkitt lymphoma.[10,11] Despite the histologic differences, Burkitt and Burkitt-like lymphoma/leukemia are clinically very aggressive and are treated with very aggressive regimens.[12,13,14,15]