Gastrointestinal stromal tumours: A clinicopathological perspective

Gastrointestinal stromal tumours (GIST) account for only 1-2% of all gastrointestinal (GI) neoplasms, yet they are the most common mesenchymal tumours of the GI tract. They arise from the interstitial cells of Cajal involved in gut motility and peristaltic movement. Early events in GIST development are activating mutations in CD117/c-KIT (cytoplasmic tyrosine kinase) or PDGFRA (Platelet Derived Growth Factor Receptor Alpha), which occur in most GISTs and encode for mutated tyrosine receptor kinases that are therapeutic targets for tyrosine kinase inhibitors. A small minority of GISTs possessing neither KIT nor PDGFRA mutations may have germline mutations in succinate dehydrogenase enzyme (SDH), suggesting a potential role of SDH in the pathogenesis. Immunohistochemical detection of c-KIT, DOG1 has proven to be highly sensitive and specific in the diagnosis of GISTs. Since accurate diagnosis by pathologists is crucial for current and future therapy, it is important to recognize KIT-negative GISTs, GISTs in specific clinical conditions, GISTs with unusual morphology, and GISTs with differential immunostaining that signify mutational subtypes. This case series highlights the biology, clinical presentations, morphology, immunohistochemistry, molecular analysis, and risk assessment of GISTs.