Pathologic Histologic and Immunohistochemical Features

GISTs usually involve the outer muscular layer and therefore, are predominantly exophytic. They usually project into the abdominal cavity. Mucosal ulceration may be seen in up to 50% of cases.28 Tumor size ranges from several millimeters to larger than 30 cm. Typically, tumors are well circumscribed but lack a true capsule. They may result in significant mass effect on surrounding organs. Cut sections are pink, tan, or gray with focal areas of hemorrhage, cystic degeneration, and necrosis, especially if large. Extensive hemorrhage and necrosis may result in cavity formation, which may communicate with the gastrointestinal lumen.

GISTs usually present with moderate to high cellularity, and tumor cells vary from spindle (70% to 80%) to epithelioid (20% to 30%).16'27 Spindle cell GISTs exhibit spindle cells that have elongated nuclei with tapered, blunt, or rounded ends and eosinophilic or basophilic cytoplasm. Epithelioid GISTs are composed of round or polygonal cells with central or slightly eccentric nuclei; they may show mitosis, but typically, they have a more benign clinical course than spindle cell GISTs. Histologically, GISTs with spindle-shaped cells may simulate smooth muscle tumors or nerve sheath tumors. They may also have prominent vascularity, hemorrhage, extensive hyalinization, or myxoid degeneration.

The biologic behavior of GISTs ranges between benign and malignant, and the differentiation is based on size, location, cellularity, and the degree of mitotic activity. Generally, malignant GISTs are large and more cellular than benign GISTs. However, the critical size is not agreed upon. Tumor behavior varies significantly by location, and the cutoff tumor size also varies by location. GISTs arising from the stomach are more likely to be benign than malignant.10 Gastric GISTs that are smaller than 5 cm in maximum diameter, with five or fewer mitoses per 50 consecutive high-power fields, have a low risk for metastasis, and are considered benign. Gastric GISTs that are larger than 10 cm and with more than five mitoses per 50 high-power fields are considered malignant. Tumors that fall between these two categories have indeterminate malignant potential. Tumors with high mitotic activity (more than 50 mitoses per 50 high-power fields) are considered aggressive with high-grade malignant potential.29 GISTs that arise from the small intestine tend to be more aggressive than those arising from the stomach. Most esophageal, colonic, and anorectal GISTs are malignant. Because benign-appearing GISTs may recur or metastasize, it has been recently suggested to classify GISTs into very low, low-, intermediate-, and high-risk categories rather than as benign or malignant.30 Careful clinical and imaging follow-up is therefore advised for all patients.30,31

The diagnosis of GIST requires confirmation with immunostaining for CD 117, which is expressed by all GIST, both spindle and epithelioid type,6 regardless of their anatomic site or clinical behavior. The presence and expression of CD 117 is also found in the interstitial cells of Cajal, which are the pacemaker cells of the gastrointestinal tract. This association suggests that these cells are the common origin of GISTs.4 The expression of CD 117 is the most specific marker for GIST.30 However, it is not pathognomonic, as other malignant neoplasms, including malignant melanoma, seminoma, sarcoma, and some leukemias, may also express CD 117.6 Fortunately, the distinction between GISTs and other tumors that express CD 117 can be made histologically. Approximately 70% to 80% of GISTs also express CD34, which is a hemopoietic progenitor cell antigen. GIST may also express smooth muscle antigen in approximately one-third of cases, but it is rarely reactive to desmin, present in true smooth muscle tumors, and S-100 immunostaining, present in schwannoma.

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