Gastrointestinal stromal tumors in Japanese patients with neurofibromatosis type I.

Toshirou Nishida,Masahiko Tsujimoto,Tsuyoshi Takahashi,Seiichi Hirota,Mari Wataya-Kaneda,Jean-Yves Blay

doi:10.1007/s00535-015-1132-6

Abstract

BackgroundNeurofibromatosis type I (NF1) predisposes patients to various neoplasias, including gastrointestinal stromal tumors (GISTs). Little is known about the risk of developing GISTs for NF1 patients or the clinicopathologic features and prognosis of NF1-GIST.MethodsWe conducted a multi-detector computed tomography screen for adult NF1 patients between 2003 and 2012. Clinicopathologic data of sporadic GISTs from patients who underwent surgery between 2001 and 2010 were retrospectively collected from 32 hospitals in Japan.ResultsCT screening identified 6 GIST patients from the 95 NF1 patients screened, suggesting that the prevalence rate of GISTs was approximately 6.3/100 in NF1 patients. All 6 NF1 patients exhibited hyperplasia of the interstitial cells of Cajal in the adjoining small intestine. NF1-GISTs may account for 1.1–1.3 % of primary sporadic GISTs and present as multiple tumors in the small intestine, with low mitotic activity and no KIT or PDGFRA mutations. The risk of recurrence and mortality is very similar between NF1 and non-NF1 patients after surgical resection of GISTs.ConclusionsNF1 patients may be predisposed to developing small intestinal GISTs, which may appear as multiple GISTs without KIT and PDGFRA mutations. The prognosis of patients with NF1-GISTs is similar to patients with conventional GISTs.Electronic supplementary materialThe online version of this article (doi:10.1007/s00535-015-1132-6) contains supplementary material, which is available to authorized users.

Highlights

Gastrointestinal stromal tumors (GISTs) predominantly occur in the stomach (60–70 %) and small intestine (20–30 %), and multiple tumors are rarely observed [1, 2].J Gastroenterol (2016) 51:571–578gastrointestinal stromal tumors (GISTs) proliferation may be caused by gain-of-function mutations in either the KIT (80–85 %) or PDGFRA (10 %) genes [2]
Several retrospective studies have reported an increased risk for GISTs in NF1 patients, most reports have suffered from small sample sizes
One epidemiologic study using the Swedish Cancer Registry estimated that the lifetime risk of an NF1 patient developing GISTs could be as high as 7 % [3, 11]

Summary

Introduction

Gastrointestinal stromal tumors (GISTs) predominantly occur in the stomach (60–70 %) and small intestine (20–30 %), and multiple tumors are rarely observed [1, 2]. GIST proliferation may be caused by gain-of-function mutations in either the KIT (80–85 %) or PDGFRA (10 %) genes [2]. Five to ten percent of GISTs lack mutations in these genes (wild-type GISTs). A selective tyrosine kinase inhibitor of KIT, PDGFR-a, and Abl, exhibits exceptional activity in advanced GIST patients. The benefits of imatinib have largely been observed in KIT- and PDGFRAmutant GISTs; its activities are less well documented in wild-type GISTs [2]. Little is known about the risk of developing GISTs for NF1 patients or the clinicopathologic features and prognosis of NF1-GIST.

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Conclusion