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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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 - Jan 1 2014

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Enteropathy-Associated T-Cell Lymphoma
Japan
Lymphocytes
Mitogen-Activated Protein Kinases
Extracellular Signal-Regulated MAP Kinases
Lymphoma
Neoplasms
Proto-Oncogene Proteins c-met
Fluorescence In Situ Hybridization
Natural Killer Cells
Small Intestine
Atrophy
Cell Survival
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan. / Kikuma, Kanta; Yamada, Kozue; Nakamura, Shotaro; Ogami, Akiko; Nimura, Satoshi; Hirahashi, Minako; Yonemasu, Hirotoshi; Urabe, Shogo; Naito, Shinji; Matsuki, Yasumasa; Sadahira, Yoshito; Takeshita, Morishige.

In: Human Pathology, Vol. 45, No. 6, 01.01.2014, p. 1276-1284.

Research output: Contribution to journalArticle

Kikuma, K, Yamada, K, Nakamura, S, Ogami, A, Nimura, S, Hirahashi, M, Yonemasu, H, Urabe, S, Naito, S, Matsuki, Y, Sadahira, Y & Takeshita, M 2014, 'Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan', Human Pathology, vol. 45, no. 6, pp. 1276-1284. https://doi.org/10.1016/j.humpath.2013.10.038
Kikuma, Kanta ; Yamada, Kozue ; Nakamura, Shotaro ; Ogami, Akiko ; Nimura, Satoshi ; Hirahashi, Minako ; Yonemasu, Hirotoshi ; Urabe, Shogo ; Naito, Shinji ; Matsuki, Yasumasa ; Sadahira, Yoshito ; Takeshita, Morishige. / Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan. In: Human Pathology. 2014 ; Vol. 45, No. 6. pp. 1276-1284.
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