Tumor site appears to be associated with distinct chromosomal imbalances; for example, gastric GISTs show predominantly losses 14q, whereas intestinal GISTs more frequently

exhibit losses of 15q (95). Clinical presentation Most GISTs remain ‘silent’ until reaching a large size. Symptoms vary according to location and size. Symptomatic GIST patients generally present with nonspecific symptoms including abdominal pain, fatigue, dyspepsia, nausea, anorexia, weight Inhibitors,research,lifescience,medical loss, fever and obstruction. Patients may present with chronic GI or overt bleeding due to mucosal ulceration or tumor rupture with life-threatening intraperitoneal hemorrhage. Some patients with large GISTs may have externally palpable masses (96,97). Aggressive GISTs have a defined pattern of metastasis to the liver and throughout the Inhibitors,research,lifescience,medical abdomen or both (45). Lymph node metastasis is not common. Spreading to the lung and bone in advanced cases has been reported (98). Metastasis often occurs 10-15 years after initial surgery (45). More than 80% of GISTs are primarily located in GI tract and may occur throughout the GI tract with extra-GI tract GISTs reported in omentum, mesentery, retroperitoneum, gallbladder and urinary bladder (99-101). The majority of GISTs (60%) are seen in the stomach, usually in the

fundus (35,39). The percentages of GISTs found in other portions of GI tract are reported as 30% in jejunum and ileum, Inhibitors,research,lifescience,medical 5% in duodenum, 4% in colorectum,

and rarely in the esophagus and appendix (45,46,48,65). Reported tumor size in the stomach varies from a few millimeters to >40 Inhibitors,research,lifescience,medical cm with a mean size of 6 cm in the largest reported series (65). Apparently, the tumor size is one of the factors contributing to the clinical symptoms. A population-based study Inhibitors,research,lifescience,medical showed that the tumor size is 8.9 cm in patients with clinical symptoms, which is about 70% of GISTs studied, 2.7 cm in patients without clinical symptoms, 20%, and 3.4 cm in patients with GISTs detected at autopsy, 10% (35). Many smaller GISTs are detected incidentally during endoscopy, surgery, or computed tomography (CT) scans (35). Astemizole Diagnosis The diagnostic evaluation of GISTs is based on imaging techniques (Figure 2), with a special role of endoscopic examination because it is usually accessible when tumors are in the stomach, esophagus and large intestine. In addition, endoscopic ultrasonography (EUS) also plays an important role in the diagnostic MLN8237 work-up of GISTs and is accurate and efficient in the diagnosis of GISTs (102). In general, externally bilging tumors are more common than intraluminal masses (103). Punch-out ulcer is the classical appearance of a submucosal tumor (104). Figure 2 Computed tomography scan revealed a partially exophytic, dumbbell shaped solid mass (arrow) arising from the posterior aspect of the gastric fundus along the greater curvature, measuring approximately 6.7 cm × 4.