Epstein-Barr virus is present in neoplastic cytotoxic T cells in extranodal, and predominantly in B cells in nodal T non-Hodgkin lymphomas

Epstein-Barr virus (EBV)-positive T non-Hodgkin lymphomas (T-NHLs) have bee n described, but it is at present unknown how EBV infects T lymphocytes, It has been postulated that cytotoxic T cells (CTLs) or natural killer (NK) c ells can be infected by EBV during the killing of an EBV-infected target ce ll. The objective of this study was therefore to determine whether the neop lastic cells in EBV-positive T-NNLs (n = 221) of various locations have a c ytotoxic phenotype, To identify EBV-harbouring cells, combinations were use d of EBV-encoded RNA (EBER) in situ hybridization (RISH) and immunohistoche mistry for T- and B-cell markers and the cytotoxic proteins TIA-1 and granz yme B. EBV was detected in the neoplastic cells of all nasal T-NHLs (n = 9) , 5/34 gastrointestinal (GI) T-NHLs, and 2/6 lung T-NHLs, but not in primar y cutaneous T-NHLs (n = 103). Moreover. EBV was found in the neoplastic cel ls of 2/48 nodal anaplastic large cell lymphomas (ALCLs), but not in neopla stic T cells of other nodal T-NHLs. However, 5/17 nodal peripheral T-NHLs n ot otherwise specified (PTCLs NOS) and 1/4 T-prolymphocytic leukaemias did contain EBV-positive non-T cells. Double staining revealed that in EBV-posi tive extranodal T-NHLs (n = 16), the EBER-positive cells had a cytotoxic ph enotype (TIA-1- and/or granzyme B-positive), In nodal non-ALCL T-NHLs, the EBER-positive cells were not positive for TIA-1 or granzyme B, nor did they express CD3, CD21 or HECA452. Instead, most of these cells expressed the B -cell marker CD20. These PTCLs NOS with EBER-positive cells showed features of AILD-like T-NHL. It is concluded that neoplastic cells of EBV-positive extranodal T-NHLs always have a cytotoxic phenotype, supporting the view th at EBV can infect CTLs. In nodal non-ALCL T-NHL, EBV is only found in T-NHL with AILD-like features and is present in B cells, where it may contribute to the outgrowth of a malignant B-cell clone. Copyright (C) 2000 John Wile y & Sons, Ltd.