Anatomic location may be helpful in differential diagnosis. Intramural leiomyomas most commonly locate in the esophagus and are rare in the stomach and small intestine (126). Morphologically, leiomyomas have brightly eosinophilic cytoplasm with distinct cell borders whereas GISTs

usually reveal syncytial cell morphology. Immunohistochemically, GISTs and leiomyomas share some markers, such as SMA and Inhibitors,research,lifescience,medical h-caldesmon, but spindle cell GISTs are rarely positive for desmin which is more specific for leiomyomas. Rare epithelioid GISTs that lack KIT expression do stain positive for desmin (116). Leiomyomas are negative for CD117. Although gastric schwannomas are not commonly seen, they can be morphologically very similar to certain spindle cell GISTs. Distinct peripheral Inhibitors,research,lifescience,medical cuffing of lymphocytes and strong reactivity with S-100 and GFAP readily differentiate them from GIST in addition to the negativities of CD117 and CD34 (127). Mesenteric fibrous lesions can be very challenging in terms of diagnosis of itself and confusion with GIST due to the location and gross appearance. Microscopically, intraabdominal desmoid fibromatosis Inhibitors,research,lifescience,medical usually display long sweeping fascicles of spindle cells embedded within a collagen matrix with an infiltrating patter at peripheral of the tumor. Immunohistochemical stain of beta-catenin is positive in about 75% of cases (128-130).

Inflammatory myofibroblastic tumors are commonly seen in pediatric or young adult patients and recognized as a mesenteric mass. Microscopically, this Inhibitors,research,lifescience,medical tumor has cellular fascicular fibroblastic/myofibroblastic proliferation with a prominent mixed inflammatory components including significant number of plasma cells. About 50% of tumors express ALK-1 (131), which is essentially negative in GIST. Inflammatory fibroid polyp is a polypoid lesion of mucosa with collagenous or Inhibitors,research,lifescience,medical myxoid stroma admixed with fibroblasts. It can be CD34 positive but should be negative for CD117 and DOG1 (113,114,132). Interestingly, same PDGFRA mutations

as seen in GISTs are also discovered in inflammatory fibroid polyps (133). Histologically, epithelioid Isotretinoin GISTs need to be distinguished from other epithelial or epithelioid tumors including carcinoma, melanoma, glomus tumor, germ cell tumor and clear cell sarcoma. Immunohistochemical studies play a major rule on the differential diagnosis and the evaluation of appropriate immunophenotypic markers in context with morphology in most cases allows an accurate classification (Table 1). Table 1 Immunophenotypic features of gastrointestinal mesenchymal tumors Role of molecular analysis Mutational analysis of the KIT gene including exons 11, 9, 13, and 17, and PDGFRA gene including exons 12, 14, and 18 can be helpful in confirming the diagnosis of GISTs if immunohistochemical studies fail to support the diagnosis (particularly in CD117/DOG1-negative spindle cell learn more suspect cases).