Approximately 15% of all childhood cancers diagnosed in the United States are lymphomas. Sixty percent of all childhood lymphomas have been classified as non-Hodgkin lymphoma, representing 3% of all childhood malignancies for children younger than age 5 years, and 8% to 9% for children and adolescents 5 to 19 years of age. In the United States, 750 to 800 cases of non-Hodgkin lymphoma are diagnosed annually in children and young adults younger than 20 years of age. There is a two- to threefold increase in frequency of childhood non-Hodgkin lymphoma in males as compared to females. The incidence of non-Hodgkin lymphoma in white children is approximately twice that found in African American children, with approximately 9.2 cases per million versus 4.6 cases per million (white vs black children).^1–3 The incidence of non-Hodgkin lymphoma in children who are younger than 15 years of age has been fairly constant over the past two decades, while there has been an overall increase in the incidence in adolescents, ages 15 to 19 years.⁴ There is also an increased incidence of non-Hodgkin lymphomas, especially B-cell lymphomas, in children with inherited and/or acquired immunodeficiencies. Specific, primary, or inherited immunodeficiencies associated with an increased risk of non-Hodgkin lymphoma include Wiskott-Aldrich syndrome, severe combined immune deficiency, ataxia-telangiectasia, and common variable immune deficiency.^5–8 Patients on immunosuppressive medication, especially those following solid-organ transplantation, children with acquired immunodeficiency syndrome (AIDS), and children following allogeneic stem cell transplantation that used certain methods of in vitro allogeneic stem cell T-cell depletion are another large group of children susceptible to an increased risk of developing B-cell lymphomas.^5–8

Traditionally, non-Hodgkin lymphoma has been classified into low, intermediate, or high grade, and more recently by morphologic, immunologic, and molecular and genetic variables. Additional subclassification has divided non-Hodgkin lymphomas according to their spectrum of clinical behavior with two major subgroups: indolent or aggressive. Over the past 30 years, the most common histologic classifications of childhood non-Hodgkin lymphoma have included the morphologic schema developed by Rappaport, the morphologically and immunologically based schema of Lukes and Collins, the Kiel classifications, the prognostic subgrouping of the National Cancer Institute's Working Formulation, and the most recently developed classification that uses morphologic, immunophenotypic, and genetic information in the Revised European-American Lymphoma (REAL) classification.^5–13 The vast majority of childhood non-Hodgkin lymphomas are high-grade tumors with aggressive clinical behavior. In contrast, the majority of adult non-Hodgkin lymphomas are low to intermediate grade, indolent tumors.^{2, 3, 5} Currently, there are four major subtypes of childhood non-Hodgkin lymphoma: small noncleaved-cell (Burkitt and non-Burkitt), lymphoblastic, large-cell lymphoma, and anaplastic large-cell lymphoma (ALCL). The distribution of these four main histologic subtypes includes approximately 40% small noncleaved cell, 30% lymphoblastic, 20% B-large cell, and 10% anaplastic large-cell lymphoma (Table 141e-1).¹⁴

Table 141e-1

Non-Hodgkin Lymphoma in Children.