PEComa of the gastrointestinal tract: clinicopathologic study of 35 cases with evaluation of prognostic parameters

Perivascular epithelioid cell tumors (PEComas) are distinctive mesenchymal neoplasms that most often arise in the retroperitoneum, visceral organs, and abdominopelvic sites and usually show reactivity for melanocytic and smooth muscle markers. Fewer than 20 PEComas of the gastrointestinal (GI) tract have been reported, and behavior and criteria for malignancy are incompletely defined. The purpose of this study was to examine the clinicopathologic features of a series of GI PEComas and to evaluate prognostic parameters. A total of 35 PEComas of the GI tract were retrieved from consult and surgical files. Clinical and pathologic features were evaluated, and immunohistochemical analysis was performed. Clinical follow-up information was obtained from medical records and referring physicians. Nineteen patients were female and 16 male (median age 45 y; range, 7 to 70 y). One patient had tuberous sclerosis. Nineteen tumors arose in the colon, 12 in the small bowel, 2 in the stomach, and 1 each in gallbladder and omentum. Median tumor size was 6.2 cm (range, 0.8 to 22 cm). Three tumors were limited to the mucosa and submucosa, 8 extended to the muscularis propria, 15 to the subserosa/serosa, and 8 into the mesentery. The tumors were composed of nests and sheets of usually epithelioid cells with abundant granular eosinophilic to clear cytoplasm, surrounded by a delicate capillary vasculature. Thirteen tumors had mixed epithelioid and spindle cell components, and 2 were purely spindled. Sixteen tumors showed marked nuclear atypia. Seventeen tumors contained occasional pleomorphic cells, and 12 showed diffuse cellular pleomorphism. The median mitotic rate was 2/10 HPF (range, 0 to 36). Vascular invasion was present in 5 cases, and 16 tumors showed necrosis. By immunohistochemistry, 23/35 were positive for HMB45, 23/34 for melan-A, 15/25 for MiTF, 20/35 for smooth muscle actin, 26/35 for desmin, and 3/20 for TFE3. Focal cytoplasmic S100 protein was present in 5/27 cases, 2/25 cases were positive for KIT, and 1 case each was positive for EMA and keratin. Follow-up information was available for 31 patients (median 36 mo; range, 2 to 176 mo). Thirteen patients have developed metastases (10 liver, 3 peritoneum, 4 lymph node, 3 lung, 1 bone, 1 brain, and 1 adrenal). Thus far, 5 patients have died of disease. Metastases were significantly associated with marked atypia, diffuse pleomorphism, and mitoses ≥2/10 HPF. In summary, PEComas of the GI tract occur at similar frequency in female and male patients, most commonly involve the colon, and exhibit variable clinical behavior, ranging from benign lesions to aggressive, high-grade sarcomas. The presence of marked nuclear atypia, diffuse pleomorphism, and mitotic activity are the strongest predictors of malignant behavior.