Elsevier

Human Pathology

Volume 28, Issue 6, June 1997, Pages 674-685
Human Pathology

Original contribution
Hepatosplenic γδ T-cell lymphoma: ultrastructural, immunophenotypic, and functional evidence for cytotoxic T lymphocyte differentiation,☆☆

https://doi.org/10.1016/S0046-8177(97)90176-3Get rights and content
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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 analysis 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 Vδ1 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 × 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 yS T cell subsets.

Keywords

peripheral T-cell lymphoma
hepatosplenic lymphoma
γδ T-cell
cytotoxic T lymphocyte
cytolytic granules
perforin
granzyme B
TIA-1
Fas ligand (CD95L)

Abbreviations

TCL
T cell lymphoma
PTCL
peripheral T cell lymphoma
TCR
T cell receptor
MHC
major histocompatibility complex
IFN
interferon
CTL
cytotoxic T lymphocyte
NK
natural killer
LAK
lymphokine-activated killer
FasL
Fas ligand
FSIP
frozen section immunoperoxidase
PIP
paraffin immunoperoxidase
GM-CFU
granulocyte-monocyte colony-forming unit
i
isochromosome
ALL
acute lymphoblastic leukemia
FcR
immunoglobulin Fe receptor
Ig
immunoglobulin
DAB
diaminobenzidine
IL
interleukin
E
effector
T
target
LDH
lactate dehydrogenase
CHOP
cyclophosphamide, doxorubicin, vincristine, prednisone
PHA
phytohemagglutinin
PMA
phorbol myristate acetate

Cited by (0)

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

☆☆

Presented in part at the Annual Meeting of the United States and Canadian Academy of Pathology, San Francisco, CA, March, 1994.