Plexosarcoma

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.EDAR (EDAR hypohidrotic ectodermal dysplasia) 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. 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 between 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.:1065 For example, some previous diagnoses of stomach and small bowel leiomyosarcomas (malignant tumor of smooth muscle) would be reclassified as GISTs on the basis of immunohistochemical staining. All GIST tumors are now considered to have malignant potential, and no GIST tumor can be definitively classified as 'benign'. Hence, all GISTs are eligible for cancer staging in the AJCC (7th edition) / UICC. Nonetheless, different GISTs have different risk assessments of their tendency to recur or to metastasize, dependent on their site of origin, size, and number of mitotic figures. Due to the change in definition, clinical pathways of care before the year 2000 are largely uninformative in the current era. GISTs may present with trouble swallowing, gastrointestinal bleeding, or metastases (mainly in the liver). Intestinal obstruction is rare, due to the tumor's outward pattern of growth. Often, there is a history of vague abdominal pain or discomfort, and the tumor has become rather large by time the diagnosis is made. GISTs are tumors of connective tissue, i.e. sarcomas; unlike most gastrointestinal tumors, they are nonepithelial. About 70% occur in the stomach, 20% in the small intestine and less than 10% in the esophagus. Small tumors are generally benign, especially when cell division rate is slow, but large tumors disseminate to the liver, omentum and peritoneal cavity. They rarely occur in other abdominal organs. GISTs 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. Most GISTs 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 GIST, 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 GIST and paraganglioma, that is caused by germline mutations in the mitochondrial tumor suppressor gene pathway involving the succinate dehydrogenase (SDH) subunits SDHD, SDHC and SDHB. Approximately 85% GISTs 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 GISTs are associated with constitutive activity of the KIT enzymatic pathway, found by immunoblotting.:1062 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 GIST, arising from ICC cells.