title: Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan.
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.
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, 81400180, Japan.
authors.forename: Kanta
authors.initials: K
authors.lastname: Kikuma
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, 81400180, Japan.
authors.forename: Kozue
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 814858, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, 81400180, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ogami
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, 81400180, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nimura
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 814858, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Hirahashi
authors.affiliation: Second Pathology Laboratory, Oita Red Cross Hospital, Oita, 8700033, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Yonemasu
authors.affiliation: Pathology Laboratory, Oita Prefectural Hospital, Oita, 8708511, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Urabe
authors.affiliation: Pathology Laboratory, National Organization Ureshino Hospital, Ureshino, 8430393, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Naito
authors.affiliation: Pathology Laboratory, Kenwakai Otemachi Hospital, Kitakyushu, 8038543, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Matsuki
authors.affiliation: Department of Pathology, Kawasaki Medical School, Kurashiki, 7010192, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Sadahira
authors.affiliation: Department of Pathology, Faculty of Medicine, Fukuoka University, Fukuoka, 81400180, Japan. Electronic address: m-take@adm.fukuoka-u.ac.jp.
authors.forename: Morishige
authors.initials: M
authors.lastname: Takeshita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058527:Enteropathy-Associated T-Cell Lymphoma / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007564:Japan; D008297:Male; D008875:Middle Aged
keywords: Bcl2; Enteropathy; Enteropathy-associated T-cell lymphoma; Fluorescence in situ hybridization; MAPK; MEK; c-Met; c-Myc