The many faces of Hodgkin's disease around the world: what have we learned from its pathology?

In the past decade there have been many advances in our understanding of Hodgkin's disease. Among the most important is the discovery that the Reed-Sternberg cell is a lymphoid cell, in most cases a B cell, and that it is clonal, and thus a true lymphoma, deserving of a name change, to 'Hodgkin's lymphoma' (HL). Based on a combination of immunophenotype and morphology, the R.E.A.L. Classification recognizes two main types of HL: classical types (nodular sclerosis, mixed cellularity, lymphocyte-rich classical HL, and lymphocyte depletion) and nodular lymphocyte predominance type (NLPHL), which probably represent distinct biological entities. The immunophenotype and genetic features of both classical HL and NLPHL have been defined. These are useful in the subclassification of HL and in distinguishing HL from two recently-described, aggressive lymphomas that were in the past often diagnosed as HL: anaplastic large-cell lymphoma, T-cell type (ALCL), and T-cell/histiocyte-rich large B-cell lymphoma (T/HRBCL). Epstein-Barr virus has been detected in approximately 40% of the cases of classical HL, and is clonal, suggesting that this virus may play a role in the pathogenesis of at least some types of HL. The frequency of HL varies in different populations, and the frequency of EBV-positive HL appears to be inversely related to the overall frequency of HL in a given population. Thus, it is possible that its presence may simply reflect the prevalence of EBV-infected B cells in the individual. Despite the advances of the past ten years, many questions remain to be answered, and these will provide the challenges of the next decade.