Compound Clear Cell Sarcoma of the Skin—A Potential Diagnostic Pitfall

The proliferation of cells with melanocytic lineage and a nested pattern has traditionally been regarded as a characteristic feature of a wide range of benign and malignant melanocytic proliferations. Herein, we report a series of 4 clear cell sarcomas, including 3 primary cutaneous and 1 metastatic to the skin, associated with a clear-cut intraepidermal proliferation of tumor cells representing a serious potential diagnostic pitfall. All patients were male individuals, aged from 17 to 71 years (mean: 42 y). The size of the tumors ranged from 8 to 55 mm (mean: 22.2 mm, median: 13 mm). Two tumors arose on a lower extremity and 1 each on the scalp and chest. Cutaneous metastasis developed on the limb proximal to the amputation site. Histologically, all tumors were variably circumscribed nodular or multinodular proliferations within the dermis, focally extending into the subcutis. They were composed of nests and fascicles of pale spindled and epithelioid cells with finely granular or pale cytoplasm, elongated nuclei with a single prominent nucleolus, featuring mild nuclear pleomorphism, and surrounded by delicate fibrous septa. Scattered wreath-like giant cells were present in all cases. Mitotic activity was low (mean and median: 3.5 mitoses/mm2). The intraepidermal component consisted in all 4 cases of nests of tumor cells localized at the dermal-epidermal junction. Nests were well-defined and composed of spindled or epithelioid cells with irregular hyperchromatic nuclei, prominent nucleoli, and scant to moderately abundant eosinophilic to pale cytoplasm. Lentiginous proliferation of epithelioid tumor cells was coupled with focal upward migration of isolated tumor cells in a single case. By immunohistochemistry, all tumors were S100 protein, melan A, and HMB45 positive. By fluorescence in situ hybridization analysis, 3 tumors displayed rearrangements in the EWSR1 gene, whereas reverse transcriptase polymerase chain reaction confirmed EWSR1(e8)/ATF1(e4) translocation in the remaining case. In conclusion, an epidermal component in primary cutaneous clear cell sarcomas, or cutaneous metastasis of the tumor, is exceptional and represents a potential diagnostic pitfall. Careful attention to the salient morphologic features in the dermal component of the tumor, as well as confirmation of EWSR1 gene rearrangement by fluorescence in situ hybridization or reverse transcriptase polymerase chain reaction, is necessary for correct recognition of the tumor and to avoid erroneous diagnosis of a benign or malignant melanocytic proliferation.