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Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study

Tawatchai Pongpruttipan, Sanya Sukpanichnant, Thamathorn Assanasen, Pongsak Wannakrairot, Paisarn Boonsakan, Wasana Kanoksil, Kanita Kayasut, Winyou Mitarnun, Archrob Khuhapinant, Udomsak Bunworasate, Teeraya Puavilai, Anan Bedavanija, Adriana Garcia-Herrera, Elias Campo, James R Cook, John Choi, Steven H Swerdlow
American Journal of Surgical Pathology 2012, 36 (4): 481-99
22314189
Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of αβ or γδ type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 γδ enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) β,γ and, in cases tested, δ negative (presumptive NK origin); 5% were TCR γδ, 3% were TCR αβ, 1% were TCR αβ/γδ, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only αβ T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with γδ EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal γδ EATL.

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