Hepatosplenic γδ T-cell lymphoma: Ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation

Kevin E. Salhany, Michael Feldman, Marc J. Kahn, David Peritt, Richard D. Schretzenmair, Darren M. Wilson, Robert S. Dipaola, Alan D. Glick, Jeffrey A. Kant, Peter C. Nowell, Malek Kamoun

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Hepatosplenic γδ 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 analysts of three hepatosplenic γδ 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. γδ T cell receptor (TCR) expression and clonal TCRδ gene rearrangements were documented in each case. Two different subsets of γδ TCL were identified based on δ chain variable region usage; two lymphomas were Vδ1+, whereas the third was negative for both V 1/2 and Vδ2. Cytogenetic analysis was performed on two lymphomas; isochromosome 7q and probable trisomy 8 was shown in one of the Vδ1+ lymphomas, whereas the Vδ1 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+, Vδ1+ lymphomas, whereas IFNγ secretion was induced by anti-CD3 in the CD56-, Vδ1 negative lymphoma. These studies show that hepatosplenic γδ TCLs have CTL differentiation, retain functional activity in vitro, and are derived from at least two δ T cell subsets.

Original languageEnglish
Pages (from-to)674-685
Number of pages12
JournalHuman Pathology
Volume28
Issue number6
DOIs
StatePublished - 1997

Bibliographical note

Funding Information:
Supported in part by grant no. IRG-135L from the American Cancer Society (KES) and a McCabe Fund Award (KES).

Keywords

  • Cytolytic granules
  • Cytotoxic T lymphocyte
  • Fas ligand (CD95L)
  • Granzyme B
  • Hepatosplenic lymphoma
  • Perforin
  • Peripheral T-cell lymphoma
  • TIA-1
  • γδ T-cell

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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