Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin

Abstract

We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T- cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation.

Primary CD30‐positive cutaneous T‐cell lymphomas and lymphomatoid papulosis frequently express cytotoxic proteins

“…29,30 We and others have already demonstrated that ␥␦ T-cell lymphomas are derived from cytotoxic ␥␦ T-cells. 18,23,31 These cells can be regarded as a first line of immunodefense in various mucosal and epithelial sites. 32 The absence of cytotoxic proteins in tumour cells of most of CD30 negative cutaneous T-cell lymphomas was also observed in mycosis fungoides and in Sezary syndrome, in which cells with a cytotoxic profile had the appearance of reactive lymphocytes 33,34 (personal data).…”

Is there truly a risk of lymphoma from biologic therapies?

“…As there is no effective therapy for HSTCL, all cases were fatal. HSTCL is a rare clinicopathological entity, usually of cytotoxic, gd T-cell origin (53). Although the incidence of this disease is unknown, about 200 cases have been reported since its first description in 1981.…”

Hepatosplenic γδ T‐cell lymphoma: relation to Epstein–Barr virus and activated cytotoxic molecules

“…1,2 Most postthymic neoplasms that arise from this ␥␦ T-cell subpopulation can be classified as hepatosplenic ␥␦ lymphomas. [3][4][5][6] On the other hand, only a few cases of non-hepatosplenic ␥␦ lymphoma have been reported. 7,8 Hepatosplenic ␥␦ T-cell lymphoma is a rare, recently described subset of peripheral T-cell lymphomas characterized by hepatosplenomegaly without lymphadenopathy, clinically significant cytopenia and an aggressive clinical course.…”

“…7,8 Hepatosplenic ␥␦ T-cell lymphoma is a rare, recently described subset of peripheral T-cell lymphomas characterized by hepatosplenomegaly without lymphadenopathy, clinically significant cytopenia and an aggressive clinical course. [3][4][5][6] These lymphomas preferentially infiltrate hepatic sinusoids and splenic red pulp but may also involve lymph node sinuses, bone marrow and peripheral blood. 5,6 Non-hepatosplenic ␥␦ T-cell lymphoma can be regarded as a model of lymphoma derived from activated cytotoxic cells, occurring in mucosa or skin.…”