Abstract

A 5-year-old girl presented with an enlarging scalp mass and cervical lymphadenopathy. Histopathology showed a dermal-based neoplasm with subcutaneous extension, sparing the epidermis. Cells were monomorphic with moderate eosinophilic cytoplasm and round nuclei with vesicular chromatin and prominent nucleoli. The cells were arranged in sheets and vague nests showing frequent mitotic figures and focal tumor necrosis. Immunohistochemistry showed diffuse SOX10 expression; MART-1 staining was pale and patchy, HMB-45 was rare, and S100 protein was essentially negative. The Ki-67 index was elevated at 30%. Stains for pan-cytokeratin, p63, smooth muscle actin, myogenin, and desmin were negative. INI1 and BAP1 were retained, BRAF V600E staining was negative, H3K27me3 was variable (retained), and PRAME was negative. Sequencing showed an EPHA7 mutation. Further molecular studies were negative for fusions involving EWSR1, FUS, CRTC1, or TRIM11, but instead revealed a novel MED15::ATF1 fusion. Copy number gains of 12q13 and 22q11, including both MED15 and ATF1 loci, were also detected. Gene expression clustering grouped this lesion with cutaneous melanocytic tumors with CRTC1-TRIM11 fusion (CMTCT). Although the location, immunophenotype, and gene expression features were more typical of a CMTCT, the aggressive presentation with clinically suspected nodal metastases and an ATF1 fusion suggested behavior similar to clear cell sarcoma. Thus, treatment based on a clear cell sarcoma protocol was suggested. Treatment with nivolumab and ipilimumab had already been initiated due to a working diagnosis of melanoma; only limited clinical follow-up is available to date.