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. KIT and PDGFRA mutations account for 85-90% of GIST carcinogenesis. However, the remaining 10-15% of GISTs, which until recently were called KIT/PDGFRA wild-type GISTs, have been found to have one of the several mutations, including in the SDHA, B, C, D, BRAF and NF1 genes. 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 in KIT, PDGFRA, SDH subunits and NF1. 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.

Are gastrointestinal stromal tumours really asymptomatic?

“…Positivity for CD117 (the C-kit marker) is very common [2,3]. In our case series, the CD117 and CD34 positivity rates were 92.3% and 50%, respectively, similar to rates described in the literature [7,8].…”

“…Arthur Purdy Stout [6] first described GISTS, which are mesenchymal tumours thought to originate from the precursors of Cajal intestinal cells [2]. Positivity for CD117 (the C-kit marker) is very common [2,3].…”

“…GISTs are thought to originate from precursors of Cajal cells, which regulate peristalsis in the gastrointestinal tract. Mutations in the Ckit or platelet-derived growth factor receptor alpha proto-oncogenes often play roles in GIST pathogenesis [2]. However, some GISTs lack detectable mutations [3].…”

Screening populations at high risk for soft tissue sarcoma and surveillance following soft tissue sarcoma resection

“…A small subset of GISTs (10%) harbor mutations in the platelet‐derived growth factor receptor alpha ( PDGFRA ) gene, which confers increased chance of imatinib resistance. In the remaining 10% of GISTs, additional mutated genes identified include NF‐1 , succinate dehydrogenase complex subunits ( SDH ), and the B‐raf proto‐oncogene …”

Intestinal tumors in neurofibromatosis 1 with special reference to fatal gastrointestinal stromal tumors (GIST)

“…In NF1, the development of GISTs has been shown to result from the inactivation of both alleles of NF1 gene (Maertens et al, ). Other pathogenic mechanisms of GISTs include mutations of succinate dehydrogenase complex subunits, or rare mutations in genes such as BRAF, PIK3CA, CBL, or KRAS (Gopie et al, ; Wada, Arai, Kure, Peng, & Naito, ).…”