Epstein-Barr virus infections and Hodgkin's disease: a study of fixed tissues using the polymerase chain reaction

Epstein-Barr viral (EBV) infections are associated with Hodgkin's disease (HD). To better characterize this relationship, fixed tissues of infectious mononucleosis, normal and reactive lymph nodes, lymph nodes with progressively transformed germinal centers, and biopsy specimens with the different subtypes of HD were analyzed by polymerase chain reaction (PCR). The presence or absence of EBV, the relative amounts of EBV, and the presence of multiple EBV genotypes as defined by amplification of a polymorphic EBV locus were determined for each specimen. Epstein-Barr virus could be detected from all specimens with infectious mononucleosis (eight of eight cases), generally in relatively large amounts, with multiple EBV genotypes evident in two cases. Epstein-Barr virus could not be detected from normal or reactive lymph nodes (none of 39 cases). Small amounts of EBV could be detected from a minority of cases with progressively transformed germinal centers (two of 16 cases), with multiple EBV genotypes evident in one case. Variable amounts of EBV could be detected from approximately half of the specimens with HD (26 of 50 cases). Epstein-Barr virus was most often detected in the subtypes of mixed cellularity (12 of 15 cases), nodular sclerosis (seven of 14 cases), and lymphocyte depletion (five of seven cases) compared with nodular lymphocyte predominance HD (two of 14 cases). In contrast to specimens with infectious mononucleosis and progressively transformed germinal centers, only one EBV genotype was evident in the specimens with HD. These findings are consistent with the hypothesis that some cases of HD may be directly associated with EBV.