Abstract

A 61-year-old man presented with an enlarging mass on his fourth digit, prompting a punch biopsy. Histologic analysis revealed a dermal-based proliferation of relatively monomorphic cells arranged in haphazard fascicles. The cells exhibited moderate eosinophilic cytoplasm, elongated nuclei with finely dispersed chromatin, and inconspicuous nucleoli. There was no evidence of overt cytologic atypia, mitotic figures, or necrosis. Immunohistochemistry showed strong, diffuse positivity for the ERG stain and patchy (10-15%) strong nuclear staining for the SATB2 stain. The cells were negative for the CD34, Factor XIIIa, SOX-10, S100, and EMA stains. These histomorphological and immunohistochemical features led to consideration of an EWSR1::SMAD3 rearranged fibroblastic tumor. To assess gene fusions, the Anchored Multiplex PCR (AMPTM) FUSION-SEQer platform was utilized. Although no fusions were detected, RNA sequencing uncovered an exon 7 skipping alteration in the ERG gene which was confirmed by RT-PCR and Sanger sequencing. ERG expression plays a crucial role in regulating transforming growth factor β (TGF-β) and SMAD3, which are involved in mesenchymal differentiation. Exon 7 skipping in ERG has been previously linked to prostate cancer progression. This is the first reported case of an ERG alteration as a potential alternative mechanism related to the histomorphological spectrum of fibroblastic tumors involving the SMAD3 gene.