Persistent active herpes virus infection associated with atypical polyclonal lymphoproliferation (APL) and malignant lymphoma

This study focuses on lymphoproliferative diseases associated with persistent infection by Epstein-Barr virus (EBV) and human herpes virus 6 (HHV-6). A suggestive premalignant lymphoproliferative state is distinguished from malignant lymphoma and identified as "atypical polyclonal lymphoproliferation" (APL). Sixteen cases of herpes virus (HHV)-associated APL are compared with 21 cases of HHV-associated malignant lymphomas (ML), with 108 cases of EBV or HHV-6 related acute infections mononucleosis, with 14 cases of seronegative non-specific lymphoid hyperplasia and with 304 cases of HHV-unrelated ML. Six cases of APL and two ML occurred in AIDS patients, two cases in Sjogren's syndrome, one in a kidney allograft recipient, and the remaining cases had no identified underlying disease. APL was histologically reminiscient of excessive infectious mononucleosis, while other cases of Castleman's disease or even of malignant lymphoma. Seropositive APL and ML contained significantly more virus genome than is found in latent background infection. There was no histologic difference between HHV-6 or EBV-positive APL or ML, although both viruses infect different lymphocyte populations. From histology alone, seropositive ML cases were not distinguished from seronegative ones, yet persistent active EBV and HHV-6 appear to predominate in follicular center cell- and immunoblastic lymphoma and in HOdgkin's disease. Although no a direct oncogenic activity of these viruses could be observed in our cases, they may contribute to lymphomagenesis by inducing progressive lymphoproliferation.