Non-Hodgkin lymphomas (NHLs) comprise approximately 10% of all childhood cancers and are a diverse collection of malignant neoplasms of lymphoreticular cells [1]. Pediatric NHL includes a varied group of neoplasms that derive from both mature and immature (blastic) cells of both B-cell and T-cell origin (Table 21.1). NHLs in children are typically intermediate to high-grade (clinically aggressive) tumors. This is in direct contrast to NHL in adults, in which more than two-thirds of the tumors are indolent, low-grade malignancies [2–5]. Pediatric NHL also appears very different from adult lymphomas in that nearly all of the tumors are diffuse neoplasms, and follicular (nodular) lymphomas are exceedingly rare. Pediatric NHL is nearly evenly split between B-cell and T-cell neoplasms, whereas in adults nearly 80% of NHLs are of B-cell phenotype. In addition, pediatric populations have a high incidence of precursor (lymphoblastic) lymphomas, whereas nearly all adult lymphomas arise from mature B- and T-cells [3–4, 6–8].

Diagnosis of pediatric NHL requires similar approaches to those used in adults. Pediatric NHLs are usually aggressive, fast-growing neoplasms that require efficient and appropriate handling of pathologic materials to ensure that a diagnosis can be established (Table 21.2) [9–10]. Morphology and immunophenotype provide the cornerstones of diagnosis, with some problematic cases requiring additional diagnostic ancillary testing, including cytogenetics (to identify specific recurrent cytogenetic abnormalities) or molecular studies (to determine clonality or specific translocations).