title: Gastrointestinal stromal tumors of neurofibromatosis type I (von Recklinghausen's disease).
abstract: Gastrointestinal stromal tumor (GIST), as well as the hyperplastic lesions of intestinal neural tissue and its supporting structures, is a gastrointestinal complication of type 1 neurofibromatosis (NF1) (von Recklinghausen's disease). In the present study, we analyzed the histologic and immunohistochemical features, and the c-kit and PDGFRA gene mutations of 36 GISTs derived from 9 NF1 patients. Distinctively, multiple GISTs arose preferentially in the small intestine. The histologic features of NF1-associated GISTs are almost similar to those of non-NF1 GISTs, but characteristically most of the NF1-associated GISTs contained skeinoid fibers. Thirty-three GISTs (92%) showed immunoreactivity for KIT, and 23 tumors (64%) showed diffuse or mosaic-like immunoreactivity for S-100 protein. Hyperplasic lesions, which may be the hyperplasia of interstitial cells of Cajal, were observed around some GISTs. Exons 9, 11, 13, and 17 of the c-kit gene and exons 12 and 18 of the PDGFRA gene were amplified and directly sequenced. Point mutations of c-kit gene or PDGFRA gene were identified only in three (8%) and two (6%) tumors, respectively. NF1-associated GISTs, showing the dual differentiation of interstitial cells of Cajal and Schwann cells, develop in close association with the myenteric nerve structure of gastrointestinal tract of NF1 patients. The point mutations of c-kit and PDGFRA gene may play a limited role in the tumorigenesis of NF1-associated GISTs.
authors.affiliation: Department of Human Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Takazawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Sakurai
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Ikeda
authors.forename: Jun
authors.initials: J
authors.lastname: Yamaguchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hashizume
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Motegi
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009456:Neurofibromatosis 1 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha