ArticleVirchows Archiv : an international journal of pathology2026
Cutaneous basaloid neoplasms with epithelial differentiation and EWSR1-fusions: a series of four cases.
Article in Virchows Archiv : an international journal of pathology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
EWSR1::FLI1 is an established oncogenic driver of Ewing sarcoma, a malignant round cell sarcoma, while EWSR1::PBX3 fusions have been associated with myoepithelioma, in particular the syncytial type, which is characterized by cutaneous predilection, syncytial growth and co-expression of S100 and EMA in the absence of cytokeratin expression. We recently reported two cases of basaloid neoplasms with adnexal differentiation harboring EWSR1::FLI1 and EWSR1::PBX3 fusions. Herein, we report four additional basaloid epithelial tumors with similar morphologic features and EWSR1 fusions. We discuss the potential overlap between these cases with syncytial myoepitheliomas, and superficial adamantinoma-like Ewing sarcoma (ALES). The cases arose on the leg (n = 2), buttock, and back in 1 female and 3 males with a median age of 30 (range: 16-84). Microscopically all tumors were dermal based neoplasm with subcutaneous involvement in two. These neoplasms consist in basaloid tumor cells with trabecular growth patterns and prominent follicular differentiation in 3. A second solid or syncytial component was observed in two cases. Immunohistochemistry revealed BerEP4 positivity as well as cytokeratin expression in all cases. RNA sequencing revealed EWSR1::PBX3 in three cases and EWSR1::FLI1 in one. Transcriptomic and methylation comparison of the cases with a control group of skin tumors revealed the EWSR1::PBX3 basaloid tumors to form a cluster distinct from syncytial myoepitheliomas with EWSR1::PBX3 fusion while the EWSR1::FLI1-rearranged case co-clustered with the Ewing sarcoma group. Our findings confirm the existence of adnexal tumors with EWSR1-fusion and further highlight the diagnostic dilemmas between these tumors and other entities with EWSR1- fusions such as syncytial myoepithelioma and ALES.
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