Pathology of Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumor (GIST) is a well recognized and relatively well understood soft tissue tumor. Early events in GIST development are activating mutations in KIT or PDGFRA, which occur in most GISTs and encode for mutated tyrosine receptor kinases that are therapeutic targets for tyrosine kinase inhibitors, including imatinib and sunitinib. A small minority of GISTs possessing neither KIT nor PDGFRA mutations may have germline mutations in SDH, suggesting a potential role of SDH in the pathogenesis. Immunohistochemical detection of KIT, and more recently DOG1, has proven to be reliable and useful in the diagnosis of GISTs. Because current and future therapies depend on pathologists, it is important that they recognize KIT-negative GISTs, GISTs in specific clinical contexts, GISTs with unusual morphology, and GISTs after treatment. This review focuses on recent developments in the understanding of the biology, immunohistochemical diagnosis, the role of molecular analysis, and risk assessment of GISTs.

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