Hodgkin lymphoma comprises 6% of childhood cancers. In the United States, the incidence of Hodgkin lymphoma is age-related and is highest among 15 to 19 year olds (29 per million per year), with children ages 10 to 14 years, 5 to 9 years, and 0 to 4 years having approximately threefold, eightfold, and 30-fold lower rates, respectively. In non-European Union countries, there is a similar rate in young adults but a much higher incidence in childhood.[4,5] The male to female ratio varies markedly by age in the pediatric population. Children younger than 5 years show a strong male predominance (M/F = 5.3) and children aged 15 to 19 years show a slight female predominance (M/F = 0.8).Lymphomas and reticuloendothelial neoplasms (ICCC II) For children and adolescents in the United States, there is an increased risk of Hodgkin lymphoma in families with higher parental incomes and higher education level. There is a lower incidence of Hodgkin lymphoma in families with large numbers of children.
Hodgkin lymphoma is characterized by a variable number of characteristic multinucleated giant cells (Reed-Sternberg [R-S] cells) or large mononuclear cell variants (lymphocytic and histiocytic [L & H] cells) in an inflammatory milieu. This inflammatory milieu consists of small lymphocytes, histiocytes, epithelioid histiocytes, neutrophils, eosinophils, plasma cells, and fibroblasts in different proportions depending on the histologic subtype. It has been conclusively shown that R-S cells and/or L & H cells represent a clonal population. Almost all cases of Hodgkin lymphoma arise from preapoptotic germinal center B cells that cannot synthesize immunoglobulin.[7,8] The R-S cell appears to be resistant to apoptotic stimuli. Deregulation of the nuclear transcription factor NFkB in the R-S cells may explain this resistance to apoptosis.
Epstein-Barr virus (EBV) genetic material can be detected in R-S cells from some patients with Hodgkin lymphoma. EBV positivity is most commonly observed in tumors with mixed-cellularity histology and is almost never seen in patients with lymphocyte-predominant histology.[9,10,11,12,13] EBV positivity is more common in children younger than 10 years [9,13] compared with adolescents and young adults.[10,11] The incidence of EBV tumor cell positivity for Hodgkin lymphoma in developed countries is 15% to 25% in adolescents and young adults.[12,13,14] There is a very high incidence of mixed-cellularity histology in childhood Hodgkin lymphoma seen in developing countries, and these cases are generally EBV-positive (approximately 80%). EBV serologic status is not a prognostic factor for failure-free survival in pediatric and young adult Hodgkin lymphoma patients.[9,12,13,14,16] Patients with a prior history of serologically confirmed infectious mononucleosis have a fourfold increased risk of developing EBV-positive Hodgkin lymphoma; these patients are not at increased risk for EBV-negative Hodgkin lymphoma. Although rare, Hodgkin lymphoma can be familial.