Table 2. Major Histopathological Categories of Non-Hodgkin Lymphoma in Children and Adolescentsa continued...
Diffuse large B-cell lymphoma
Diffuse large B-cell lymphoma is a mature B-cell neoplasm that represents 10% to 20% of pediatric NHL.[2,3,16] Diffuse large B-cell lymphoma occurs more frequently during the second decade of life than during the first decade.[2,17,18] The WHO classification system does not recommend morphologic subclassification based on morphologic variants (e.g., immunoblastic, centroblastic) of diffuse large B-cell lymphoma. Pediatric diffuse large B-cell lymphoma may present clinically similar to Burkitt or Burkitt-like lymphoma, though it is more often localized and less often involves the bone marrow or CNS.[16,17,20]
About 20% of pediatric diffuse large B-cell lymphoma presents as primary mediastinal disease (primary mediastinal B-cell lymphoma). This presentation is more common in older children and adolescents and has been associated with an inferior outcome compared with other pediatric diffuse large B-cell lymphoma.[13,14,17,21,22,23] In a study of adolescents with stage III primary mediastinal large B-cell lymphoma treated with FAB/LMB-96 therapy, the 5-year event-free survival (EFS) was 66%, versus 85% for adolescents with nonmediastinal diffuse large B-cell lymphoma.[Level of evidence: 2A] However, a single-arm study in adults showed excellent disease-free survival utilizing the DA-EPOCH-R regimen (dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab; usually six cycles) with filgrastim and no radiation therapy. The 5-year EFS was 93% and overall survival (OS) was 97%.[Level of evidence: 2A] At 10 years poststudy, there was no evidence of cardiac toxicity. This is currently being tested in pediatric clinical trials.
Primary mediastinal B-cell lymphoma is associated with distinctive chromosomal aberrations (gains in chromosome 9p and 2p in regions that involve JAK2 and c-rel, respectively) [22,23] and commonly shows inactivation of SOCS1 by either mutation or gene deletion.[26,27] Primary mediastinal B-cell lymphoma also has a distinctive gene expression profile in comparison with other diffuse large B-cell lymphoma, suggesting a close relationship of primary mediastinal B-cell lymphoma with Hodgkin lymphoma.[28,29]
With the exception of primary mediastinal B-cell lymphoma, diffuse large B-cell lymphoma in children and adolescents differs biologically from diffuse large B-cell lymphoma in adults. The vast majority of pediatric diffuse large B-cell lymphoma cases have a germinal center B-cell phenotype, as assessed by immunohistochemical analysis of selected proteins found in normal germinal center B cells, such as the BCL6 gene product and CD10.[18,30,31] Unlike adult diffuse large B-cell lymphoma of the germinal center B-cell type, in which the t(14;18) translocation involving the immunoglobulin heavy-chain gene and the BCL2 gene is commonly observed, pediatric diffuse large B-cell lymphoma rarely demonstrates the t(14;18) translocation. As many as 30% of patients younger than 14 years with diffuse large B-cell lymphoma will have a gene signature similar to Burkitt lymphoma. A subset of pediatric diffuse large B-cell lymphoma cases were found to have a translocation that juxtaposes the IRF4 oncogene next to one of the immunoglobulin loci. diffuse large B-cell lymphoma cases with an IRF4 translocation were significantly more frequent in children than adults (15% vs. 2%), were germinal center–derived B-cell lymphomas, and were associated with favorable prognosis compared with diffuse large B-cell lymphoma cases lacking this abnormality.