Pathogenesis and etiology of cutaneous NK/T lymphoproliferative disorders

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In order to elucidate the EBV gene expression, we examined 8 patients with cutaneous EBV-related NK/T-cell lymphomas, including 6 patients with NK-cell phenotypes and 2 patients with T-cell phenotypes. All samples from the patients contained EBV nuclear antigen(EBNA)-1 mRNA which was transcribed using the Q promoter, whereas both the Q promoter and another upstream promoter (Cp/Wp) were used in 3 EBV-positive cell lines, B95.8, Raji and Jiyoye. Latent membrane protein-1 (LMP-1) mRNA was detected in 7 out of 8 patients and all cell lines, whereas EBNA-2 transcripts were found only in the cell lines. The BHRF1 (viral bcl-2 homologue) and BCRF1 (viral interleukin(vlL)-10) gene transcripts were detected in 1 (NK2) and 2 patients (NK2 and 3), respectively. The patient (NK2) with UK-cell lymphoma expressing the both transcripts died of rapid progression of the illness. No LMP-1, EBNA-2 or ZEBRA antigens were detected in the skin lesions by immunostaining although they were positive in the cell line cells.One EBV-infected NK cellI line designated NOY-1 was established from a patient with hypersensitivity to mosquito bite associated with oligoclonal proliferation of EBV-infected NK cells in the blood. Clonal expansion of the cells was observed in the cutaneous lesions following mosquito bite. The cell line cells contained 7.5 copies of EBV-DNA, and produced high levels of IFN-gamma by stimulation.