NK-cell Lineage Predicts Poor Survival in Primary Intestinal NK-cell and T-cell Lymphomas

Abstract

Most primary intestinal natural killer (NK)-cell and T-cell lymphomas (PINKTL) in the Northern Europe are enteropathy-associated T-cell lymphomas, a complication of celiac disease, which is rare in the East. Primary intestinal NK-cell lymphoma is extremely rare and is poorly characterized. We investigated 30 cases of PINKTL from Taiwan with male: female at 2:1, median age at 55.5, 80% with jejunal/ileal involvement, 77% with perforation, 27% with multicentric tumors, and 67% at stage IE. All 7 cases tested for serum IgA anti-tissue transglutaminase were negative. Only 3 (10%) tumors showed enteropathy. Six (20%) were NK-cell lymphoma and 24 (80%) were T-cell lymphoma. The tumor cells in 21/30 (70%) cases were small to medium sized, which correlated with the coexpression of both CD8 and CD56. All tumors expressed at least 1 cytotoxic marker. All 6 NK-cell lymphomas were negative for betaF1, diffusely positive for Epstein-Barr virus-encoded mRNA (EBER), and polyclonal for T-cell receptor gene rearrangement. Five (22%) of the 24 T-cell tumors expressed betaF1, 8 (35%) of the 23 tumors were positive for EBER, and 20 (95%) of the 21 tumors were clonal for T-cell receptor. The overall 1-year survival was 36%. Univariate regression analysis showed that NK-cell lineage, multicentricity, and perforation were associated with poor prognosis. NK-cell lineage (P=0.037) was a poor prognostic factor by multivariate Cox proportional hazard regression analysis. PINKTL in Taiwan is predominantly not enteropathic with a high frequency of perforation, small to medium tumor cell size and cytotoxic phenotype. Primary intestinal NK-cell lymphoma carries a very poor prognosis, and is probably a distinct entity.

Primary intestinal T-cell and NK-cell lymphomas: a clinicopathological and molecular study from China focused on type II enteropathy-associated T-cell lymphoma and primary intestinal NK-cell lymphoma

“…males (mean age 37 years), and the lymphomas were more likely to arise in the colon. As same as previous reports, 7,16 primary intestinal NK-cell lymphoma in our study had a higher incidence of intestinal perforation and was more likely to cause systemic symptoms such as fever compared with the T-cell group. In 2008, Tung et al 17 reported five primary intestinal NK-cell lymphomas based on EBER positivity and polyclonal T-cell receptor gene rearrangements using conventional clonality studies in a series of 11 primary intestinal T-cell and NKcell lymphomas.…”

“…In our study, seven tumors were considered type II enteropathy-associated T-cell lymphoma, accounting for 16 and 22% of the primary intestinal T-cell and NK-cell lymphoma and T-cell groups, respectively. These percentages are higher than those reported by Chuang et al, 16 who found only 2 type II enteropathy-associated T-cell lymphoma cases among 30 primary intestinal T-cell and NK-cell lymphomas.…”

Type II enteropathy‐associated T‐cell lymphoma: A multicenter analysis from the Asia Lymphoma Study Group

“…This observation is consistent with a recent study of EATL in 18 Chinese patients, which also showed only type II histology [10]. In several previous studies of intestinal T-cell lymphomas in Asian patients [6][7][8][9]11,12,17,18], type II EATL was also predominantly observed, although fewer than 10 cases of apparently classical EATL were described. However, the diagnosis of classical EATL in these few cases had been queried, based on the lack of stringency in diagnosis, doubtful histologic features, and immunophenotypes that would in fact be consistent with type II EATL [10].…”

“…However, the clinical, histolopathologic, and immunophenotypic features of these cases were really indistinguishable from other EBV-negative cases and to classify these cases as PTCL-NOS simply because they were EBV-positive might not be justified. Interestingly, EBV positivity has also been reported in intestinal T-cell lymphomas in other Asian patients [7]. The presence of EBV infection in a small fraction of type II EATL warrants further investigations into its pathogenetic significance.…”

“…Only a few case series of EATL have been reported from Asian populations [6][7][8][9][10][11], in whom celiac disease is rare. Interestingly, convincing cases of classical EATL cannot be identified from these publications.…”