EPSTEIN-BARR-VIRUS (EBV)-RELATED LYMPHOPROLIFERATIVE DISORDER WITH SUBSEQUENT EBV NEGATIVE T-CELL LYMPHOMA

A 58-year-old Chinese man presented initially with generalized lymphad enopathy, and lymph-node biopsy showed disturbed architecture with pre ponderance of large B-blasts mixed with numerous CD8(+) T lymphocytes, consistent with an acute Epstein-Barr virus (EBV) infection. Immunohi stological and gene rearrangement studies confirmed the absence of clo nal T or B cells. Polyclonal EBV with lytic infection was detected by Southern blot hybridization (SoBH). Expression of EBV proteins (EBNA2, LMP and ZEBRA) was detected in a proportion of cells by immunostainin g. EBV-lytic proteins EA-D, VCA, MA were also detected in rare scatter ed cells. Double immunostaining showed that the LMP-positive cells wer e of B and of T phenotype: 73% CD19(+), 26% CD2(+), 23% CD3(+), 8% CD4 (+), 17% CD8(+). After biopsy, there was spontaneous regression of lym ph-node enlargement, but lymphadenopathy recurred 8 months later, and the second lymph-node biopsy showed T-cell lymphoma, confirmed by dete ction of clonally rearranged T-cell-receptor beta-chain gene. However, EBV genome could not be detected in the second biopsy by SoBH, in sit u hybridization for EBV-encoded EBER RNA, and immunostaining for EBNA2 , LMP and ZEBRA was also negative. This case is of special interest be cause an EBV-negative T-cell lymphoma developed shortly after an acute episode of EBV-related lymphoproliferation, even though many EBV-posi tive T cells were detected during the acute episode. EBV was apparentl y not a direct cause of the lymphoma, but the close temporal associati on of the 2 lesions supports the hypothesis that EBV can act as a co-f actor in lymphomagenesis. (C) 1994 Wiley-Liss, Inc.