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 cutaneous T‐cell lymphoma of unspecified type with cytotoxic phenotype: Clinicopathological analysis of 27 patients

“…In addition, cytotoxic T‐cell lymphomas that appeared in other anatomical sites (e.g. hepatosplenic T‐cell lymphoma ( 36,37 ) and enteropathy‐type T‐cell lymphoma ( 38,39 ) ) shared aggressive clinical behavior despite an absence of any association with EBV. In contrast, cutaneous cytotoxic lymphoma cases that were unassociated with EBV appeared to be unique in their relatively favorable clinical course and spontaneous regression in some patients; thus these should be differentiated from EBV + cases.…”

Nodal, Uterine and Meningeal γδ T‐Cell Lymphomas in Cattle

“…Human γδ T‐cell lymphomas occur in limited anatomical sites, and are categorized roughly into hepatospleenic and non‐hepatospleenic types (Cooke et al., 1996; Arnulf et al., 1998). The skin, nasal cavity, larynx, lung or small bowel are initially involved in the latter type (Arnulf et al., 1998).…”

“…As they were small in number and size, the amount of perforin was considered to be too small to be detected immunohistochemically. In case 3, the negative reactivity for perforin may have been caused by post‐mortem changes or the lymphoma cells may have been functionally immature and not yet capable of cytotoxic function (Cooke et al., 1996). In humans, some hepatosplenic γδ T‐cell lymphomas, whose neoplastic cells are perforin negative, represent tumours of non‐activated cytotoxic γδ T cells (Boulland et al., 1997).…”

“…In humans, hepatosplenic γδ T‐cell lymphoma is a distinct clinicopathological entity derived from cytotoxic γδ T cells, and is characterized by involvement of the liver and spleen in a sinusoidal pattern (Cooke et al., 1996). Other γδ T‐cell lymphomas are classified into several types on the basis of the involved sites (De Wolf‐Peeters and Achten, 2000).…”

Pitfalls and major issues in the histologic diagnosis of peripheral T‐cell lymphomas: results of the central review of 573 cases from the T‐Cell Project, an international, cooperative study

“…The different entities belonging to this group have different morphological and immunophenotypical patterns and can be recognized for the diverse clinical presentation, a usually aggressive clinical course and poor response to available chemotherapy . High diversity of PTCLs reflects the diverse cells from which they can originate .…”