<unk> s are<unk> s of connective tissue, i.e. sarcomas; unlike most<unk><unk> s, they are nonepithelial. About 70% occur in the stomach, 20% in the small intestine and less than 10% in the esophagus. Small<unk> s are generally benign, especially when cell division rate is slow.<unk><unk> s commonly metastasize to the liver (in 28% of cases) and/or to the greater omentum, lesser omentum, or mesentery (in 30% of cases). Less common areas of metastasis include the lungs, subcutaneous tissue, lymph nodes or bones.<unk> s are thought to arise from interstitial cells of Cajal (ICC), that are normally part of the autonomic nervous system of the intestine. They serve a pacemaker function in controlling motility. Genetics Most<unk> s are sporadic. Less than 5% occur as part of hereditary familial or idiopathic multitumor syndromes. These include, in descending order of frequency, neurofibromatosis Recklinghausen (NF-1), Carney's triad (gastric<unk> , pulmonary chondroma and extra-adrenal paraganglioma), germline gain-of-function mutations in c-Kit/PDGFRA, and the Carney-Stratakis syndrome. The Carney-Stratakis syndrome is a dyad of hereditary<unk>  and paraganglioma, that is caused by germline mutations in the mitochondrial<unk>  suppressor gene pathway involving the succinate dehydrogenase (SDH) subunits SDHD, SDHC and SDHB. c-KIT mutations Approximately 85%<unk> s are associated with an abnormal c-KIT pathway. c-KIT is a gene that encodes for a transmembrane receptor for a growth factor termed stem cell factor (scf). The abnormal c-KIT pathway most commonly (85%) arises from mutation of the gene itself; a smaller subset of c-KIT-associated<unk> s are associated with constitutive activity of the KIT enzymatic pathway, found by immunoblotting. The c-KIT product/CD117 is expressed on ICCs and a large number of other cells, mainly bone marrow cells, mast cells, melanocytes and several others. In the gut, however, a mass staining positive for CD117 is likely to be a<unk> , arising from ICC cells. The c-KIT molecule comprises a long extracellular domain, a transmembrane segment, and an intracellular part. Mutations generally occur in the DNA encoding the intracellular part (exon 11), which acts as a tyrosine kinase to activate other enzymes. Mutations make c-KITfunction independent of activation by scf, leading to a high cell division rate and possibly genomic instability. Additional mutations are likely "required" for a cell with a c-KIT mutation to develop into a<unk> , but the c-KIT mutation is probably the first step of this process. Mutations in the exons 11, 9 and rarely 13 and 17 of the c-KIT gene are known to occur in<unk> . The tyrosine kinase function of c-KIT is important in the medical therapy for<unk> s, as described below. *KIT-D816V point mutations in c-KIT exon 17 are responsible for resistance to targeted therapy drugs like imatinib mesylate, a tyrosine kinase inhibitor. *KIT-p.D419del (exon 8) - A subset of<unk> s previously regarded as wild-type<unk> s carries somatic activating mutations in KIT exon 8 (p.D419del). PDGFRA mutations Most<unk>  cells with wildtype (i.e. not mutated) c-kit instead have a mutation in another gene, PDGFR-α (platelet derived growth factor receptor alpha), which is a related tyrosine kinase. Mutations in c-kit and PDGFrA are mutually exclusive . Wild-type<unk> s Lesser numbers of<unk> s appear to be associated with neither c-kit nor PDGFR-α abnormalities. About 10-15% of<unk> s <unk> s) carry wild-type sequences in all hot spots of KIT and platelet-derived growth factor receptor alpha (PDGFRA) (wt-GISTs). These<unk> s are currently defined by having no mutations in exons 9, 11, 13, and 17 of the KIT gene and exons 12, 14, and 18 of the PDGFRA gene.
Gastrointestinal stromal tumor
Ectopic pancreas
Krukenberg tumor
Signet ring cell carcinoma
Lipoblastoma
Nesidioblastoma
Angiomyofibroblastoma
Myxoid cyst