Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%),  PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs  stain positively for KIT (CD117). Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract. Classification
GIST was introduced as a diagnostic term in 1983.: 1060  Until the late 1990s, many non-epithelial tumors of the gastrointestinal tract were called "gastrointestinal stromal tumors". Histopathologists were unable to specifically distinguish among types we now know to be dissimilar molecularly. Subsequently, CD34, and later CD117 were identified as markers that could distinguish the various types. Additionally, in the absence of specific therapy, the diagnostic categorization had only a limited influence on prognosis and therapy. The understanding of GIST biology changed significantly with identification of the molecular basis of GIST,: 1065  particularly c-KIT. Historically, literature reviews prior to the molecular definition of GIST, and for a short time thereafter, asserted that 70-80% of GISTs were benign. The identification of a molecular basis for GIST led to the exclusion of many tumors that had been considered as GIST previously, and also the incorporation of a much larger number of tumors that had been labeled as other types of sarcomas and undifferentiated carcinomas.
Imatinib (Glivec/Gleevec), an orally administered drug initially marketed for chronic myelogenous leukemia based on bcr-abl inhibition, also inhibits both c-KIT tyrosine kinase mutations and PDGFRA mutations other than D842V, and is useful in treating GISTs in several situations. Imatinib has been used in selected neoadjuvant settings. : 23  In the adjuvant treatment setting, the majority of GIST tumors are cured by surgery, and do not need adjuvant therapy. An exception to this is where the anatomical position of the tumour means that surgery is technically difficult or complex. For example, rectal GIST often requires radical surgery to achieve complete resection, involving abdominoperineal resection and permanent stoma. In these situations, the use of neoadjuvant imatinib can significantly decrease both tumour size and mitotic activity, and permit less radical sphincter-preserving surgery.A substantial proportion of GIST tumors have a high risk of recurrence as estimated by a number of validated risk stratification schemes, and can be considered for adjuvant therapy. The selection criteria underpinning the decision for possible use of imatinib in these settings, including a risk assessment based on pathological factors such as tumor size, mitotic rate and location, can be used to predict the risk of recurrence in GIST patients. Tumors <2 cm with a mitotic rate of <5/50 HPF have been shown to have lower risk of recurrence than larger or more aggressive tumors. Following surgical resection of GISTs, adjuvant treatment with imatinib  reduces the risk of disease recurrence in higher risk groups.