Abstract

GLI1 gene alterations (rearrangement or amplification) have been found in several bone and soft tissue tumors including pericytic tumors, gastric plexiform fibromyxoma, gastroblastoma, and a various group of epithelioid tumors with regional recurrence or distant metastasis. Although previous studies have shown the presence of GLI1 mRNA and protein overexpression in basal cell carcinomas and cutaneous adnexal tumors, chromosomal alterations involving GLI1 have not been reported in other cutaneous tumors. Herein, we describe a case of primary cutaneous epithelioid mesenchymal tumor harboring hitherto not reported ATP2B4-GLI1 gene fusion. A 42-year-old man presented with a growing firm lesion on the left postauricular scalp. Microscopically, the shave biopsy specimen revealed a dermal-based nodular proliferation of relatively monotonous epithelioid cells with round to ovoid nuclei and pale eosinophilic cytoplasm, accompanied by prominent stromal vasculature. Significant cytologic atypia, necrosis and mitotic activity were absent. The tumor cells were partially positive for S-100 protein, but were negative for other markers, including SOX-10, keratins, and myogenic markers. An ATP2B4-GLI1 gene fusion was identified by next-generation sequencing. Array-CGH was also performed, but it did not show relevant chromosomal copy number changes. The patient underwent subsequent complete surgical excision. The present case might be the first example of a GLI1-rearranged mesenchymal tumor of the skin. Additionally, this study identified a novel ATP2B4-GLI1 gene fusion. Its line of differentiation and biologic potential remain uncertain. Awareness of this rare cutaneous tumor and thus reporting of additional cases is necessary for further delineating its full clinicopathologic spectrum.

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