Table 2. Major Histopathological Categories of Non-Hodgkin Lymphoma in Children and Adolescentsa continued...
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] 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.[24,25] 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.[26,27]
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.[18,28,29] 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.
Lymphoblastic lymphoma comprises approximately 20% of childhood NHL.[2,3,17] Lymphoblastic lymphomas are usually positive for TdT, with more than 75% having a T-cell immunophenotype and the remainder having a precursor B-cell phenotype.[3,31] Chromosomal abnormalities are not well characterized in patients with lymphoblastic lymphoma.
As many as 75% of patients with lymphoblastic lymphoma will present with an anterior mediastinal mass, which may manifest as dyspnea, wheezing, stridor, dysphagia, or swelling of the head and neck. Pleural effusions may be present, and the involvement of lymph nodes, usually above the diaphragm, may be a prominent feature. There may also be involvement of bone, skin, bone marrow, CNS, abdominal organs (but rarely bowel), and occasionally other sites such as lymphoid tissue of Waldeyer ring and testes. Abdominal involvement is less than observed in Burkitt lymphoma. Low-stage lymphoblastic lymphoma may occur in lymph nodes, bone, testes, or subcutaneous tissue. Lymphoblastic lymphoma within the mediastinum is not considered low-stage disease.