Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan

Kanta Kikuma, Kozue Yamada, Shotaro Nakamura, Akiko Ogami, Satoshi Nimura, Minako Hirahashi, Hirotoshi Yonemasu, Shogo Urabe, Shinji Naito, Yasumasa Matsuki, Yoshito Sadahira, Morishige Takeshita

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22 Citations (Scopus)

Abstract

Twenty-six Japanese cases of type II enteropathy-associated T-cell lymphoma (EATL) were examined. Multiple tumors throughout the small intestine were found in 15 patients (58%) and duodenal and colonic mucosal lesions in 8 and 6 cases, respectively. Histologically, intramucosal tumor spread and a zone of neoplastic intraepithelial lymphocytes (IELs) neighboring the main transmural tumors were detected in 20 (91%) and 17 (77%) of the 22 cases examined, respectively. Inside and outside the IEL zone, some degree of enteropathy with many reactive small IELs and villous atrophy was detected in 11 cases (50%). Immunohistologically, many CD56/CD8-positive small IELs were found in the enteropathic lesions of 4 (36%) and 7 (64%) of these 11 cases. Lymphoma cells expressed tyrosine kinase receptor c-Met, serial phosphorylated (p)-mitogen-activated protein kinase/extracellular signal-regulated kinase, c-Myc, and Bcl2 in 18 (78%), 21 (91%), 11 (42%), and 19 (73%) of the total cases, respectively. By fluorescence in situ hybridization, chromosomal loci 7q31 (c-Met) and 8q24 (c-Myc) were amplified in 11 (65%) and 12 (71%) of the 17 cases analyzed. Gain of 7q31 and c-Met expression were significantly (P <.01) higher than in peripheral CD8-positive T-cell or CD56-positive natural killer-cell lymphomas. Enteropathy was seen near the IEL zone in type II EATL, and activation of the c-Met, mitogen-activated protein kinase/extracellular signal-regulated kinase-mitogen-activated protein kinase pathway, and c-Myc-Bcl2-mediated cell survival may play important roles in lymphomagenesis, converting enteropathy to type II EATL. Seven cases in the early clinical stages I and II-1 showed significantly (P <.01) better prognoses than did those in the advanced stages. Early detection of the mucosal lesions and tumors may improve patient prognosis.

Original languageEnglish
Pages (from-to)1276-1284
Number of pages9
JournalHuman Pathology
Volume45
Issue number6
DOIs
Publication statusPublished - Jun 2014

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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