HEPATOSPLENIC GAMMA-DELTA T-CELL LYMPHOMA - ULTRASTRUCTURAL, IMMUNOPHENOTYPIC, AND FUNCTIONAL EVIDENCE FOR CYTOTOXIC T-LYMPHOCYTE DIFFERENTIATION

Hepatosplenic gamma delta T cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cyt openias. Detailed clinicopathological, ultrastructural, and cytogeneti c analyses of these lymphomas are limited; functional characteristics of these lymphomas are unknown. We have undertaken a clinicopathologic al, immunophenotypic, ultrastructural, cytogenetic, and functional ana lysis of three hepatosplenic gamma delta TCLs. All patients presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or sever e neutropenia; terminal blastlike transformation occurred in one patie nt. Combination chemotherapy had no response in two patients, but indu ced complete remission in one. gamma delta T cell receptor (TCR) expre ssion and clonal TCR delta gene rearrangements were documented in each case. Two different subsets of gamma delta TCL were identified based on delta chain variable region usage; two lymphomas were V delta 1+, w hereas the third was negative for both V delta 1 and V delta 2. Cytoge netic analysis was performed on two lymphomas; isochromosome 7q and pr obable trisomy 8 was shown in one of the V delta 1+ lymphomas, whereas the V delta 1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK ce ll-associated antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocy te (CTL) effector proteins (perforin, granzyme B, TIA-1, and Fas ligan d) were expressed by each lymphoma; dense core cytolytic granules were observed by electron microscopy in both lymphomas studied. Functional studies performed in two cases showed TCR-mediated cytolysis of P815 x 2 FcR+ cells induced by anti-CDS in a redirected cytolysis assay in one of the CD56+, V delta 1+ lymphomas, whereas IFN gamma secretion wa s induced by anti-CD3 in the CD56-, V delta 1 negative lymphoma. These studies show that hepatosplenic gamma delta TCLs have CTL differentia tion, retain functional activity in vitro, and are derived from at lea st two gamma delta T cell subsets. Copyright (C) 1997 by W.B. Saunders Company.