They typically harbor KIT exon 11 mutations as seen in gastric GISTs and a small portion of small intestinal GISTs contain duplication of two codons in KIT exon 9 (86,118).
Usually, small intestinal GISTs do not harbor PDGFRA mutations. The sigmoid colon is the most common segment involved by GISTs (39) in the colon. Histopathologic profile of colonic GISTs is similar to that of small intestinal GISTs. Pediatric Inhibitors,research,lifescience,medical GISTs account for about 1-2% of GISTs. They are often misdiagnosed as having another acute or chronic MG-132 abdominal condition and they are usually symptomatic and mostly located in the stomach with mainly epithelioid pattern (35,46,50,51). GIST occurs in children and young adults as a component of two distinct syndromes: Carney triad and Carney-Stratakis syndrome. Carney triad is composed of co-occurrence of GIST, pulmonary chondroma, and paraganglioma. Carney triad can Inhibitors,research,lifescience,medical be diagnosed when any of the two tumors are present in a patient. However, if only GIST and paraganglioma are present, it is considered to be Carney-Stratakis Inhibitors,research,lifescience,medical syndrome. GIST in patients with Carney triad tends to be multifocal and have high local recurrence rate and/or metastatic rate. However, the clinical course of GIST in Carney triad is usually indolent (61). Although pediatric GISTs express KIT protein, the majorities lack KIT or PDGFRA mutations (46,50,51). In 2002, a germline-inactivating mutation in the hereditary paraganglioma
gene was found to be unique for Carbey-Stratakis Inhibitors,research,lifescience,medical (119,120). This germline mutation results in a cancer predisposition syndrome including GIST. Patients with neurofibromatosis type 1 (NF1) have a high risk for GIST. Some autopsy studies have demonstrated as many as one of three NF1 patients to have GISTs (121). NF-associated GIST typically occur in duodenum or small intestine and often multifocal Inhibitors,research,lifescience,medical and small. They commonly have low risk parameters
and are clinically indolent (57,121). In contrast to sporadic adults GISTs, NF1-associated GISTs lack KIT and PDGFRA mutations (57,121,122). Familial GISTs were reported and account for a very small portion of GISTs (<0.1%). They have typically activated germline KIT or PDGFRA mutations with an autosomal dominant inheritance and high penetrance (52,55,123,124). They occur usually in middle age of life and typical multifocal Cediranib (AZD2171) or diffuse in the GI tract. Most of these GISTs have a benign course. Differential diagnosis Although GISTs are the most common mesenchymal tumor of the GI tract, a variety of other tumors should be included in the differential diagnosis. Accurate recognition of GIST is obviously important as the treatment differs according to the tumor type. The main differential diagnoses include smooth muscle tumors, schwannoma, desmoid fibromatosis, inflammatory myofibroblastic tumor, inflammatory fibroid polyp, solitary fibrous tumor, synovial sarcoma, follicular dendritic cell sarcoma, glomus tumor, and melanoma.