GIST
Summary
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the GI tract, arising from the interstitial cells of Cajal (the GI pacemaker cells). Most cases are driven by gain-of-function mutations in the c-KIT (CD117) or PDGFRA tyrosine kinase receptors. The stomach is the most common site, and treatment involves surgical resection with imatinib (a tyrosine kinase inhibitor) for unresectable, metastatic, or high-risk disease.
Detail
GISTs originate from interstitial cells of Cajal, which normally regulate GI motility as pacemaker cells within the muscularis propria. Approximately 75-80% of GISTs harbor activating mutations in KIT (CD117), while a subset have PDGFRA mutations; a minority are wild-type for both (often associated with SDH deficiency, seen in Carney triad or Carney-Stratakis syndrome, and in NF1 patients). Immunohistochemistry is key to diagnosis: tumors stain positive for CD117 (KIT), DOG1 (discovered on GIST-1), and often CD34; they are typically negative for desmin and S-100, helping distinguish GIST from leiomyoma/leiomyosarcoma (desmin+) and schwannoma (S-100+).
Most GISTs occur in the stomach (~60%), followed by small intestine, colon/rectum, and esophagus. Clinical presentation varies from asymptomatic incidental finding to GI bleeding, abdominal pain, early satiety, or a palpable mass; they can also present with obstruction. Risk stratification for malignant potential depends on tumor size, mitotic rate, and location (per the modified NIH/Miettinen criteria).
Treatment: Complete surgical resection is first-line for localized, resectable disease. Molecular targeted therapy with imatinib (a KIT/PDGFRA tyrosine kinase inhibitor) is used for unresectable, metastatic, or recurrent disease, and as adjuvant therapy in high-risk resected tumors. Imatinib resistance can develop via secondary KIT mutations, prompting use of second-line agents like sunitinib or regorafenib.
High-yield associations: GIST is part of Carney triad (GIST, paraganglioma, pulmonary chondroma) and neurofibromatosis type 1. Unlike adenocarcinomas, GISTs arise from mesenchymal tissue, not epithelium, making them sarcomas rather than carcinomas.
Sources
- Robbins and Cotran Pathologic Basis of Disease
- First Aid for the USMLE Step 1
- Sabiston Textbook of Surgery
- UpToDate: Gastrointestinal stromal tumors
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