CYTOTOXIC PROTEIN EXPRESSION IN NATURAL-KILLER-CELL LYMPHOMAS AND IN ALPHA-BETA AND GAMMA-DELTA PERIPHERAL T-CELL LYMPHOMAS

Lymphomas with T-cell phenotype represent a heterogeneous group of dis eases differing in histopathology, tumour site, and cell origin. They include peripheral T-cell lymphomas (PTCLs) derived from alpha beta ce lls, but also some recently recognized entities such as gamma delta he patosplenic lymphomas and natural killer (NK) cell lymphomas, Only a f ew studies have investigated the possibility that at least some PTCLs could be derived from lymphocytes with cytotoxic potential, In order t o investigate this possibility, 60 cases of PTCL, including 27 cases e xpressing the alpha beta T-cell receptor (TCR alpha beta), 15 TCR gamm a delta cases acid 18 cases expressing neither TCR (TCR silent), as we ll as 14 cases of NK-cell lymphomas, were studied by immunohistochemis try for the expression of TIA-1, perforin, and granzyme B proteins. Ex pression of TIA-I is characteristic of cytotoxic cells regardless of t heir activation status, whereas expression of perforin and granzymes i s highly increased in activated cytotoxic cells and correlates with th e induction of cytolytic activity. All NK-cell lymphomas (11 sinonasal , three systemic cases) expressed TIA-1, perforin, and granzyme B in m ost tumour cells, All gamma delta PTCLs (15 cases) expressed TIA-I pro tein in most tumour cells, with a different cytotoxic antigen profile in hepatosplenic gamma delta PTCL, (TIA-1+, perforin -, granzyme B -) and in non-hepatosplenic gamma delta PTCLs (three nasal, one skin, one lung), the latter expressing the three cytotoxic proteins, Of the 45 cases of alpha beta and TCR silent PTCL, 15 (33 per cent) were conside red to be derived from cytotoxic lymphocytes with expression of at lea st one cytotoxic protein (TIA-1, 15/45; perforin, 10/41; granzyme B, 1 4/38) in tumour cells, This cytotoxic protein expression appeared to b e related to the site of localization, since 7/13 (54 per cent) extran odal and only 8/32 (25 per cent) nodal alpha beta and TCR silent PTCLs expressed TIA-1, and to histology, since this pattern was observed in a proportion of anaplastic (6/8, 75 per cent) and pleomorphic (8/17, 47 per cent) lymphomas, but nor in AILD-type NHL (0/16). Taken togethe r, our data suggest that NK-cell. lymphomas and non-hepatosplenic gamm a delta PTCLs represent tumours of activated cytotoxic NE cells and ga mma delta T cells, respectively; that hepatosplenic gamma delta PTCLs represent tumours of non-activated cytotoxic gamma delta T cells; and that a small proportion of alpha beta and TCR silent PTCLs, mostly ext ranodal cases, or nodal anaplastic lymphomas, represent tumours of cyt otoxic T cells. (C) 1997 John Wiley & Sons, Ltd.