Epstein-Barr virus (EBV)-related lymphoproliferative disorder with subsequent EBV-negative T-cell lymphoma

A 58-year-old Chinese man presented initially with generalized lymphadenopathy, and lymph-node biopsy showed disturbed architecture with preponderance of large B-blasts mixed with numerous CD8+ T lymphocytes, consistent with an acute Epstein-Barr virus (EBV) infection. Immunohistological and gene rearrangement studies confirmed the absence of clonal 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 immunostaining. EBV-lytic proteins EA-D, VCA, MA were also detected in rare scattered cells. Double immunostaining showed that the LMP-positive cells were of B and of T phenotype: 73% CD19+, 26% CD2+, 23% CD3+, 8% CD4+, 17% CD8+. After biopsy, there was spontaneous regression of lymph-node enlargement, but lymphadenopathy recurred 8 months later, and the second lymph-node biopsy showed T-cell lymphoma, confirmed by detection of clonally rearranged T-cell-receptor beta-chain gene. However, EBV genome could not be detected in the second biopsy by SoBH, in situ hybridization for EBV-encoded EBER RNA, and immunostaining for EBNA2, LMP and ZEBRA was also negative. This case is of special interest because an EBV-negative T-cell lymphoma developed shortly after an acute episode of EBV-related lymphoproliferation, even though many EBV-positive T cells were detected during the acute episode. EBV was apparently not a direct cause of the lymphoma, but the close temporal association of the 2 lesions supports the hypothesis that EBV can act as a co-factor in lymphomagenesis.