Context: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and should be differentiated from other mesenchymal tumors. They harbor specific activating mutations in the KIT or platelet-derived growth factor receptor α ( PDGFRA ) receptor tyrosine kinases, which makes them responsive to pharmacologic inhibitors, such as imatinib mesylate and sunitinib malate.
Objectives: To provide a comprehensive review of the pathogenesis of GIST and the underlying principles of targeted therapy, to review the salient histologic and immunohistochemical features that facilitate the distinction of GIST from other mesenchymal neoplasms of the gastrointestinal tract, and to present the prognostic parameters for risk stratification that guide clinical management.
Data sources: Review of the English literature through PubMed as well as personal experience. Photographs were taken from cases encountered at the Cleveland Clinic.
Conclusions: The discovery of the KIT -GIST connection has not only improved the diagnostic accuracy of GISTs but also provided us with a better understanding of the histogenesis and molecular pathogenesis of these neoplasms.