Expression of human herpesvirus-8 oncogene and cytokine homologues in an HIV-seronegative patient with multicentric Castleman's disease and primary effusion lymphoma

Human herpesvirus-8 (HHV-8) has been described in association with two lymp hoproliferative disorders: one benign, multicentric Castleman's disease (MC D), and one malignant, primary effusion lymphoma (PEL). The factors that le ad to malignant transformation of lymphoid cells are unknown, although most cases of PEL also are positive for EBV, suggesting a role for EBV as a cof actor in malignant transformation. We encountered a rare case of an HHV-8-a ssociated MCD, followed by the development of an HHV-8-positive pleural PEL and a gastric large cell lymphoma in an HIV-seronegative male patient. The lesions were negative for Epstein-Barr virus (EBV). The combination of the se diverse HHV-8-associated lymphoproliferative disorders in a single patie nt afforded us the ability to study potential differences in gene expressio n in these conditions. HHV-8 DNA was demonstrated by PCR in lymphoid tissue s involved by MCD and PEL. By reverse transcriptase-PCR, HHV-8-related tran scripts, including vG-coupled protein receptor, vbcl2, vcyclin D, vIL-6, vM IPI, and vMIPII, were detected in the PEL from the pleural cavity and the g astric lymphoma, whereas these transcripts, except for vIL-6, were not dete cted in a lymph node biopsy with MCD. Expression of hIL-10 was weak in the PEL from the pleural cavity, and expression of hIL-6 was undetectable in al l three lesions. These data suggest that vIL-6 may be integral to the patho genesis of MCD, whereas other viral transcripts that encode oncogene and ch emokine homologues are important for HHV-8 tumorigenicity.