Intestinal γδ T-cell lymphomas are most frequently of type II enteropathy-associated T-cell type

Abstract

Summary Enteropathy-associated T-cell lymphoma includes type I cases and distinctive type II cases that, according to 2008 and 2010 World Health Organization descriptions, are T-cell receptor β+. Although T-cell receptor γδ enteropathy-associated T-cell lymphomas are reported, it is unknown if they have distinctive features and if they should be categorized as enteropathy-associated T-cell lymphoma or as a mucocutaneous γδ T-cell lymphoma. To address these questions, the clinicopathologic, immunophenotypic, molecular, and cytogenetic features of 5 γδ-enteropathy-associated T-cell lymphomas were investigated. Only 1 patient had celiac disease and had type I enteropathy-associated T-cell lymphoma, and the others fulfilled the histopathologic criteria for type II enteropathy-associated T-cell lymphoma. All lacked cutaneous involvement. A celiac disease–associated HLA type was found in the patient with CD and one of four others. All were T-cell receptor γ+, T-cell receptor δ+, βF1−, CD3+, CD7+, CD5−, CD4−, and TIA-1+ with variable staining for CD2 (3/5), CD8 (2/5), Granzyme B (1/5), and CD56 (4/5). Fluorescence in situ hybridization demonstrated 9q34 gains in 4 cases, with 9q33-34 gains by single nucleotide polymorphism in 3 of these. Single nucleotide polymorphism analysis also demonstrated gains in 5q34-q35.1/5q35.1 (4/5), 8q24 (3/5), and in 32 other regions in 3 of 5 cases. Vδ1 rearrangements were identified in 4 of 4 cases with documented clonality showing the same clone in normal-appearing distant mucosa (3/3 tested cases). Thus, γδ-enteropathy-associated T-cell lymphomas share many features with other enteropathy-associated T-cell lymphoma and are mostly of type II. Their usual nonactivated cytotoxic phenotype and Vδ1 usage are features unlike many other mucocutaneous γδ T-cell lymphomas but shared with hepatosplenic T-cell lymphoma. These findings support the conclusion that a γδ T-cell origin at extracutaneous sites does not define a specific entity.

Human Peripheral Blood Gamma Delta T Cells: Report on a Series of Healthy Caucasian Portuguese Adults and Comprehensive Review of the Literature

“…Loss of CD5 expression has been considered an aberrant immunophenotypic feature, useful for identifying the neoplastic Tc, in the PB and in the involved tissues [191]. However, this characteristic may only traduce a terminal differentiation of the neoplastic Tc into CTL, as occurs in γδ Tc LGL leukemia [23], cutaneous γδ Tc lymphoma [192] and intestinal γδ Tc lymphoma [193]; or a premature loss of CD5 expression in activated, functionally-immature, cytotoxic, neoplastic Tc, as happens in hepatosplenic γδ Tc lymphoma [48].…”

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma

“…Cytogenetic studies have demonstrated gains and translocations of MYC (8q24) 10 , 13 , 16 in EITL, although they may also be seen in classical EATL. 17 Conversely, gains of 1q32.2-q41 and 5q34-q35.2 are more common in EATL compared with EITL, whereas 9q31.3 gain and 16q21.1 loss can be observed in both classical EATL and EITL. 1 , 3 Recently, it was reported that an activating STAT5B p.N642H mutation is common in T-cell lymphoma derived from γδ T-cells, including some cases of EITL.…”

SYK expression in monomorphic epitheliotropic intestinal T-cell lymphoma

“…Thus, the expression of the TCR is an indicator, though no discriminator, differentiating between MEITL and EATL with statistical significance. 37 In addition, our study adds to the notion that the loss of TCR expression is common in EATL. 34,38 As a main finding in our study, SYK is strongly expressed in the vast majority of MEITL cases.…”