An epidemiologist's view of the new molecular biology findings in Hodgkin's disease.

Recent advances in molecular biology provide new strategies to address the pathogenesis of Hodgkin's disease (HD). Immunophenotyping studies of Reed-Sternberg cells suggest lymphoid cells, 'frozen in a state of activation.' Clonal rearrangement studies find heavy and light chain immunoglobulin and beta and gamma T-cell receptor gene changes. Chromosomal studies find a complex but nonrandom mixture of structural rearrangements including many seen in other hematologic disorders. These findings are consistent with a pathogenesis involving chronic antigenic stimulation. This interpretation is supported by the epidemiologic features of HD which suggest that HD may develop as a rare consequence of infection with a common latent virus where risk is increased if infection is delayed until adolescence or young adulthood. Such 'late' infections are generally more clinically severe and may result in more chronicity of virus replication. Serologic and genome probe studies of the Epstein-Barr virus--a candidate agent--in HD specimens support this hypothesis. In summary, the new molecular biology findings in HD converge with the previous epidemiologic, immunologic, and clinical data to support a unifying hypothesis of pathogenesis in which genetic abnormalities occur secondarily to a sustained host response to chronic tissue-based antigenic stimulation.