They typically have a tan-white or fleshy pink cut surface often with hemorrhagic foci, central cystic degeneration, or necrosis (Figure 3). The overlying mucosa of large tumors is typically ulcerated (46). Figure 3 A gastric GIST with a nodulular surface and thin capusle. The cut surface reveals coarse granular and solid white tan suface with hemarrhage and cavities Histopathology Microscopically, GISTs have a broad morphological spectrum. Three main histological subtypes have been best widely accepted and they are spindle cell type Inhibitors,research,lifescience,medical (most common, 70%), epithelioid type (20-25%), and mixed spindle cell and epithelioid type (99,105,106)

Inhibitors,research,lifescience,medical (Figure 4). In general, GISTs have a wide variation ranging from hypocellular to highly cellular with higher mitotic rates. Nuclear pleomorphism is relatively uncommon, and occurs more frequently in epithelioid type. Figure 4 Common histologic al features of GISTs. A. Spindle cell

GIST with short fascicles and whorls (×100); B. Spindle cell GIST with longer fascicles in bundles (×100); C. Spindle cell GIST with extensive OSI-906 supplier perinuclear vacuolization (×100); … Spindle cell type of GIST is composed of Inhibitors,research,lifescience,medical cells in short fascicles and whorls. They have pale eosinophilic fibrillary cytoplasm, ovoid nuclei, and ill-defined cell borders. Gastric spindle cell GISTs often reveal extensive perinuclear vacuolization, a diagnostic feature formerly

used for tumors Inhibitors,research,lifescience,medical of smooth muscle origin. The stroma sometimes demonstrates myxoid change or, rarely osseous metaplasia. Distinctive histological patterns among spindle cell GISTs including sclerosing type and palisading-vacuolated type (65). The sclerosing spindle cell GISTs have slender spindle cells with no nuclear atypia and low mitotic activity and are usually paucicellular with extensive extracellular collagen. They are often small and contain calcifications. The palisading-vacuolated type is one Inhibitors,research,lifescience,medical of the most common gastric GISTs and usually cellular with plump and uniformed spindle cells. Nuclear palisading with perinuclear vacuolization is characteristic. There is usually limited atypia with mitotic Phosphatidylinositol diacylglycerol-lyase activity rarely more than 10/50 high power fields (HPFs). However, some examples show diffuse hypercellular pattern, and others sarcomatoid features with significant nuclear atypia and mitotic activity (65,99,106). Epithelioid cell GISTs are characterized by round cells arranged in nests or sheets and with eosinophilic to clear cytoplasm. They also have spectrums from sclerosing and paucicellular to sarcomatous and mitotically inactive to mitotically highly active. However, the epithelioid GISTs with atypia, even with pleomorphism are sometimes benign (65,99,106).

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