Gastrointestinal stromal tumors (GISTs) are categorized as a type of soft-tissue sarcoma and are the most common type of sarcoma arising within the GI tract. Overall, they are very rare with approximately 4000 to 6000 new cases annually in the United States (1 General references Gastrointestinal stromal tumors are tumors of the gastrointestinal tract derived from mesenchymal precursor cells in the gut wall (interstitial cells of Cajal). Diagnosis is usually by endoscopy... read more ).
GISTs result from mutations in receptor tyrosine kinases. The vast majority are caused by a mutation in the C-KIT gene, whereas some are caused by a mutation in the PDGFRA gene (2 General references Gastrointestinal stromal tumors are tumors of the gastrointestinal tract derived from mesenchymal precursor cells in the gut wall (interstitial cells of Cajal). Diagnosis is usually by endoscopy... read more ). Some are caused by previous radiation therapy to the abdomen for other tumors. The remainder are caused by a variety of less common mutations and are generally referred to as wild-type GISTs.
In one study, 51% of GISTs occurred in the stomach,36% in the small bowel, and a small number in the esophagus, colon, and rectum (3 General references Gastrointestinal stromal tumors are tumors of the gastrointestinal tract derived from mesenchymal precursor cells in the gut wall (interstitial cells of Cajal). Diagnosis is usually by endoscopy... read more ). Average age at presentation is 50 to 60.
GISTs may arise in people with a genetic syndrome. The two most common are
Familial SDH deficiency (Carney-Stratakis syndrome)
GISTs are often slow growing, but they exhibit a wide array of malignant potential. The malignant potential of a particular GIST is related to where in the GI tract it originates, the size of the primary tumor, and the mitotic rate seen on biopsy (or surgical pathology). Of these, small tumors in the stomach with a low mitotic rate have the most favorable outcomes. Those measuring < 2 cm have very low malignant potential (2 to 5%) and are often managed by observation.
Symptoms of GISTs vary with location but include bleeding, dyspepsia Dyspepsia Dyspepsia is a sensation of pain or discomfort in the upper abdomen; it often is recurrent. It may be described as indigestion, gassiness, early satiety, postprandial fullness, gnawing, or burning... read more , and obstruction. They are also commonly identified incidentally on imaging that is done for another reason.
General references
1. Cancer.Net: Gastrointestinal Stromal Tumor—GIST: Statistics. Accessed August 1, 2023.
2. Heinrich MC, Corless CL, Duensing A, et al: PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299(5607):708-710, 2003. doi: 10.1126/science.1079666
3. Tran T, Davila JA, El-Serag HB: The epidemiology of malignant gastrointestinal stromal tumors: An analysis of 1,458 cases from 1992 to 2000. Am J Gastroenterol 100(1):162–168, 2005. doi: 10.1111/j.1572-0241.2005.40709.x
Diagnosis of GISTs
Endoscopy
Diagnosis of GISTs is usually by endoscopy, with biopsy and endoscopic ultrasonography for staging.
Immunohistochemistry with positive staining for CD117 (C-KIT) and DOG-1 are pathognomonic for the diagnosis of GIST.
Once diagnosed, all patients require complete staging with CT of the chest, abdomen, and pelvis.
Treatment of GISTs
Surgical removal
Treatment of GISTs is surgical removal. Patients with metastatic disease (most commonly to the liver) may also be candidates for surgery depending on the degree of liver involvement, tumor size, and surgical resectability.
The tyrosine kinase inhibitor imatinib can be used when tumors are positive for the KIT protein CD117; it is effective for patients with unresectable and/or metastatic malignant GISTs and also as adjuvant treatment following resection in adults (1 Treatment reference Gastrointestinal stromal tumors are tumors of the gastrointestinal tract derived from mesenchymal precursor cells in the gut wall (interstitial cells of Cajal). Diagnosis is usually by endoscopy... read more ). Imatinib is also frequently given before surgery to shrink borderline resectable tumors and make surgery possible or easier. For imatinib-refractory tumors, sunitinib and regorafenib can be used.
Avapritinib, another tyrosine kinase inhibitor, should be used as first-line therapy for patients with a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.
Treatment reference
1. Dematteo RP, Ballman KV, Antonescu CR, et al: Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: A randomised, double-blind, placebo-controlled trial. Lancet 373(9669):1097–1104, 2009. doi: 10.1016/S0140-6736(09)60500-6. Clarification and additional information. Lancet 374(9688):450, 2009.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
imatinib |
Gleevec |
sunitinib |
Sutent |
regorafenib |
Stivarga |
avapritinib |
AYVAKIT |
