title: Hepatosplenic gammadelta T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation.
abstract: Hepatosplenic gammadelta T cell lymphoma (TCL) is a rare, aggressive subset of peripheral TCL that presents with hepatosplenomegaly and cytopenias. Detailed clinicopathological, ultrastructural, and cytogenetic analyses of these lymphomas are limited; functional characteristics of these lymphomas are unknown. We have undertaken a clinicopathological, immunophenotypic, ultrastructural, cytogenetic, and functional analysis of three hepatosplenic gammadelta TCLs. All patients presented with massive hepatosplenomegaly and anemia, thrombocytopenia, or severe neutropenia; terminal blastlike transformation occurred in one patient. Combination chemotherapy had no response in two patients, but induced complete remission in one. gammadelta T cell receptor (TCR) expression and clonal TCRdelta gene rearrangements were documented in each case. Two different subsets of gammadelta TCL were identified based on delta chain variable region usage; two lymphomas were Vdelta1+, whereas the third was negative for both Vdelta1 and Vdelta2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vdelta1+ lymphomas, whereas the Vdelta1 negative lymphoma had 14p+ with t(1;14)(q21;p13). NK cell-associated antigens (CD11c, CD16, or CD56) and cytotoxic T lymphocyte (CTL) effector proteins (perforin, granzyme B, TIA-1, and Fas ligand) 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-CD3 in a redirected cytolysis assay in one of the CD56+, Vdelta1+ lymphomas, whereas IFNgamma secretion was induced by anti-CD3 in the CD56-, Vdelta1 negative lymphoma. These studies show that hepatosplenic gammadelta TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two gammadelta T cell subsets.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine and Wistar Institute Philadelphia 19104, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Salhany
authors.forename: M
authors.initials: M
authors.lastname: Feldman
authors.forename: M J
authors.initials: MJ
authors.lastname: Kahn
authors.forename: D
authors.initials: D
authors.lastname: Peritt
authors.forename: R D
authors.initials: RD
authors.lastname: Schretzenmair
authors.forename: D M
authors.initials: DM
authors.lastname: Wilson
authors.forename: R S
authors.initials: RS
authors.lastname: DiPaola
authors.forename: A D
authors.initials: AD
authors.lastname: Glick
authors.forename: J A
authors.initials: JA
authors.lastname: Kant
authors.forename: P C
authors.initials: PC
authors.lastname: Nowell
authors.forename: M
authors.initials: M
authors.lastname: Kamoun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D053804:Granzymes; D006168:Guinea Pigs; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D054353:Perforin; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism* / Q000648:ultrastructure; D012697:Serine Endopeptidases / Q000378:metabolism; D013160:Splenic Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D000074019:T-Cell Intracellular Antigen-1; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D054353:Perforin; D015847:Interleukin-4; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases