INI1 and GLUT-1 Expression in Epithelioid Sarcoma and Its Cutaneous Neoplastic and Nonneoplastic Mimics

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
The American Journal of dermatopathology (Impact Factor: 1.39). 05/2009; 31(2):152-6. DOI: 10.1097/DAD.0b013e31818a5c4f
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The morphological features of epithelioid sarcoma may closely mimic those of epithelial neoplasms, such as squamous cell carcinoma, mesenchymal tumors, such as benign fibrous histiocytoma, and nonneoplastic lesions, such as granuloma annulare. Immunohistochemistry, particularly for epithelial markers and CD34, thus plays a valuable role in the differential diagnosis of epithelioid sarcoma. However, some epithelioid sarcomas may show very focal or even absent expression of such markers and may be difficult to distinguish from various morphological mimics. There is therefore continued interest in the development of new immunohistochemical markers of epithelioid sarcoma. Recently, loss of expression of INI1, a tumor suppressor gene/protein, and expression of GLUT-1, a glucose transporter protein, have been described in epithelioid sarcoma. We examined the utility of immunohistochemistry for INI1 and GLUT-1 in the diagnosis of epithelioid sarcoma and various cutaneous mimics. Twenty-four cases of epithelioid sarcoma, 13 cases of granuloma annulare, 10 cases of rheumatoid nodule, 19 cases of cutaneous squamous cell carcinoma, 7 cases of atypical fibroxanthoma, 9 cases of benign fibrous histiocytoma (dermatofibroma), and 3 cases of nodular fasciitis were immunostained for GLUT-1 and INI1 using commercially available antibodies, heat-induced epitope retrieval, and the Dako Envision detection system. Total or near-total loss of normal constitutive expression of INI1 protein was noted in more than 85% of epithelioid sarcomas, with 19 of 24 cases (79%) showing complete loss of INI1 expression. In contrast, all other cases studied showed uniformly retained expression of INI1. GLUT-1 was positive in 40%-50% of epithelioid sarcomas, all cases of granuloma annulare and rheumatoid nodules, 67% of benign fibrous histiocytomas, and in all squamous cell carcinomas. In contrast, atypical fibroxanthomas and cases of nodular fasciitis were consistently GLUT-1 negative. We conclude that immunohistochemistry for INI1 expression should be included as part of the routine immunohistochemical panel for the diagnosis of epithelioid sarcoma, along with established markers such as wide-spectrum cytokeratins, cytokeratin 5/6, p63, and CD34. In this clinical context, loss of INI1 expression seems to be an entirely specific marker of epithelioid sarcoma and this finding may be of great value in distinguishing CD34-negative epithelioid sarcoma from squamous cell carcinoma and in the distinction of rare cytokeratin-negative epithelioid sarcomas from necrobiotic processes, nodular fasciitis, and benign fibrous histiocytomas. In contrast, there does not seem to be a role for GLUT-1 immunohistochemistry in this differential diagnosis.

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    • "Glut1, a glucose transporter protein, was positive in our case and has been reported positive in about 50% of ES but has little value in the differential diagnosis from its dermal mimics as it is also expressed in granuloma annulare and rheumatoid nodules, in benign fibrous histiocytomas and squamous cell carcinomas while it is negative in atypical fibroxanthomas and nodular fasciitis [17]. Finally, the negativity of our case for glypican-3 is a finding consistent with previous reports for this marker in distal ES. "
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    ABSTRACT: Distal epithelioid sarcoma is a rare and slowly growing tumor that usually develops in the upper extremities of young adults. Neoplastic cells have both spindle and epithelioid appearance and are characterized by the loss of the nuclear protein SMARCB1/INI1. We present the case of a distal epithelioid sarcoma arising in the thumb of a 14-year-old girl, which immunohistochemically was characterized by the loss of SMARCB1/INI1 protein as well as the expression of podoplanin (D2-40), TLE1, Glut1, and Ca 125; plus, we highlight the differential diagnosis of epithelioid sarcoma from its histological mimics.
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    ABSTRACT: Epithelioid sarcoma of proximal type (ESPT), a subtype of epithelioid sarcoma, is an uncommon malignant neoplasm of the soft tissue with histo- and cytologic features similar to epithelioid sarcoma, classic type and to the more commonly encountered extra-renal malignant rhabdoid tumor (EMRT). Unlike classic epithelioid sarcoma, ESPT usually involves pelvic, perineal, and genital regions and has an aggressive clinical course. Like EMRT, ESPT can have aberrations of the INI1 gene on chromosome 22q, which results in the loss of INI1 protein expression. We describe here the cytological findings of an ESPT metastatic to the scalp in a 14-year-old boy. Cytological preparations showed a discohesive population of pleomorphic ovoid to polygonal cells with large irregular nuclei and prominent nucleoli. Isolated cells with rhabdoid features were noted. These cells had abundant cytoplasm and occasional intracytoplasmic hyaline inclusions. In the light of the patient's clinical history of a known primary ESPT of the maxilla, the cytologic features were distinct enough to render a diagnosis of a metastatic lesion to the skull.
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