Gastrointestinal Stromal Tumors: Review on Morphology, Molecular Pathology, Prognosis, and Differential Diagnosis

Abstract

Context.—Gastrointestinal stromal tumors (GISTs) are specific, generally Kit (CD117)-positive, mesenchymal tumors of the gastrointestinal tract encompassing a majority of tumors previously considered gastrointestinal smooth muscle tumors. They are believed to originate from interstitial cells of Cajal or related stem cells. Objective.—To review current clinicopathologically relevant information on GIST. Data Sources.—Literature in Medline and authors' own experience. Conclusions.—GISTs usually occur in older adults (median age 55–60 years) and rarely in children in the second decade (502-Tyr⁵⁰³ duplication is specific for intestinal GISTs. Mutations in PDGFRA have been identified in juxtamembrane (exon 12) and tyrosine kinase domains (exons 14 and 18), nearly exclusively in gastric GISTs, mostly in epithelioid variants. Some Kit and PDGFRA mutations have a prognostic value. Kit/PDGFRA tyrosine kinase inhibitor imatinib has been successfully used in the treatment of metastatic GISTs for more than 5 years. However, primary and acquired secondary resistance linked to certain types of Kit and PDGFRA mutations is limiting long-term success necessitating the use of alternative treatments.