Classification of gastrointestinal stromal tumor syndromes

Abstract

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, thought to derive from neoplastic outgrowth of the interstitial cells of Cajal. Building on recent advances in recognition, classification and diagnosis, the past two decades have seen a changing paradigm with molecular diagnostics and targeted therapies.KITandPDGFRAmutations account for 85–90% of GIST carcinogenesis. However, the remaining 10–15% of GISTs, which until recently were calledKIT/PDGFRAwild-type GISTs, have been found to have one of the several mutations, including in theSDHA,B,C,D,BRAFandNF1genes. Though most of such GISTs are sporadic, a number of families with high incidence rates of GISTs and other associated clinical manifestations have been reported and found to harbor germline mutations inKIT,PDGFRA,SDHsubunits andNF1. The goal of this review is to describe the mutations, clinical manifestations and therapeutic implications of syndromic and inherited GISTs in light of recent studies of their clinicopathologic range and pathogenesis.