Expression of Melanoma Antigens in Epithelioid Gastrointestinal Stromal Tumors: A Potential Diagnostic Pitfall (Report)
Gastrointestinal stromal tumors (GISTs) are CD117/c-kit-immunoreactive mesenchymal neoplasms that arise in the GI tract as well as abdominal soft tissues with no connection to the tubular gut. (1,2) The stomach, followed by the small intestine and the colon, are the most commonly involved sites; the esophagus is rarely involved. About 25% of gastric GISTs are malignant, and just more than 90% express CD117/c-kit in the largest published series of gastric GIST. (3) In various studies, prognosticators of malignancy were found to be a mitotic rate of more than 5 per 50 high-powered fields, a size of more than 5 cm, and the presence of mucosal invasion. The likelihood of malignant behavior is also strongly influenced by anatomic location (small bowel, colon, and esophageal GISTs all have a worse prognosis than GISTs of the stomach). (3-6) Most GISTs are spindle cell tumors and can usually be distinguished from most other common spindle cell lesions in the GI tract (smooth muscle tumors, nerve sheath tumors, inflammatory myofibroblasts tumor, spindle cell carcinomas) on the basis of histologic and immunohistochemical characteristics. A second, less common histologic variant, the epithelioid GIST, is most commonly mistaken for epithelioid and epithelial neoplasms, such as melanoma and signet ring carcinoma. Although CD117/c-kit is very useful in establishing a diagnosis of GIST, other neoplasms can also occasionally express this marker, such as a subset of melanoma, dermatofibrosarcoma protuberans, solitary fibrous tumor, synovial sarcoma, and fibromatoses, among others. (2,7-9) Among these, probably mesenteric fibromatosis is most likely to result in a misdiagnosis of GIST by spurious labeling with CD117/c-kit antibodies, depending on antigen retrieval technique, (7-9) but melanoma can also be a congener of GIST, particularly epithelioid examples. In fact, between approximately 20% and 65% of melanomas are reported to express CD117/c-kit, (7,10-12) and in one study of purely metastatic melanomas, 63% were CD117/c-kit reactive, (10) although kit protein immunolabeling in the absence of KIT gene mutations is a function of the particular antibody and conditions used. (11,13) Because of the known pitfalls of relying on a single antibody for important differential diagnoses, pathologists often apply a panel of immunohistochemical stains to confirm a diagnostic impression. Recognizing that the capacity of metastatic melanoma involving the gastrointestinal tract to mimic GIST is amplified by its likelihood of expressing CD117/c-kit, we evaluated the most commonly used “melanoma markers” in a set of well-characterized gastric GISTs from which we had prepared tissue microarrays (TMAs)14 to learn whether GIST can express antigens traditionally used to confirm an impression of melanoma. After reviewing results of the TMA studies, we performed further Melan-A labeling on 15 additional (separate) standard sections of epithelioid GIST. MATERIALS AND METHODS
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