These tumors express the cell-surface transmembrane receptor c-KIT that has tyrosine kinase activity and is the protein product of the KIT proto-oncogene (1). GIST are rare tumors with an incidence of 1.5/100,000/year with EGIST being <5% of the total. There

is a well-known correlation between NF1 and GIST as GIST develops in 7% of patients with NF1. The occurrence of NF1 is 150-180 times more frequent in GIST than in the general population. However, it is known that NF1- associated and sporadic GIST have different pathogenesis. EGIST are very rare mesenchymal tumors which originate in sites outside #KU-57788 clinical trial keyword# the gastrointestinal tract, with clinico-pathological and molecular profiles similar to GIST. The most common sites of EGIST

are the retroperitoneum, the mesentery and the omentum (2). However, other less frequent Inhibitors,research,lifescience,medical sites have also been reported such as the gallbladder, the pancreas and the recto-vaginal septum. The EGIST comprise a group of aggressive stromal tumors; their behavior is similar to those of GIST of distal location. It is unusual to diagnose EGIST when they are small due to their atypical location and vague symptomatology (2). Goh et al. in a series of 8 cases found average tumor size of 14.8 cm at Inhibitors,research,lifescience,medical the time of diagnosis (3). NF1-associated GIST appears to be a different entity than sporadic GIST (4). NF1 patients develop GIST at a younger age (median, 49 years) than individuals

with sporadic GIST (median, 56 years). There Inhibitors,research,lifescience,medical is some female predominance for NF1-associated GIST, in contrast to a weak male predominance for patients with sporadic GIST. Also in terms of distribution, GIST in NF1 occur Inhibitors,research,lifescience,medical predominantly in the small intestines, unlike sporadic GIST of which 60% arise in the stomach (4). The occurrence of multiple GIST is notably common in NF1 patients, and it is very uncommon among patients with sporadic GIST (4). It has been reported that c-KIT activation occurs in all cases of GIST, regardless of the mutational status of KIT (4). In a study by Miettinen et al, no mutations were detected in the genomic DNA of KIT (exons 9, 11, 13, 17) or PDGFRA (exons 12, 18) in NF1 associated GIST, whereas sporadic GIST have a high frequency of such activating mutations (4). In sporadic GIST, these mutations are Terminal deoxynucleotidyl transferase thought to be central events in tumorigenesis, and their occurrence even in minimal GIST <1 cm in diameter indicates them to be an early pathogenetic event. In regard to KIT mutations, Kinoshita et al. also reported no KIT mutations in 21 GIST in 7 patients with NF1 (such as in our patient described above). Lack of GIST-specific mutations suggests that the pathogenesis of GIST in NF1 patients is different from that of KIT or PDGFRA-driven GIST. The diagnosis of GIST relies on morphology and immunohistochemistry.