A MAZ::NCOA2 Subcutaneous Small Round Cell Sarcoma of Infancy With Diffuse S100/SOX10 Positivity: A Novel Entity

ABSTRACT Small round cell sarcomas (SRCSs) constitute a heterogeneous group of high‐grade tumors with a poor prognosis, predominantly affecting children and young adults. According to the 2020 WHO Soft Tissue Tumor classification, SRCSs are categorized into Ewing sarcoma, round cell sarcoma with EWSR1 ‐non‐ETS fusions, CIC ‐rearranged sarcoma, and sarcoma with BCOR genetic alterations. Herein, we report a case of a 10‐month‐old boy presenting with a progressively enlarging left lumbar mass. Histopathological examination revealed a well‐demarcated lesion composed of small, round to oval cells with scant cytoplasm and mildly irregular nuclei. Immunohistochemical staining demonstrated strong, diffuse positivity for S100 and SOX10, indicating neurocristic differentiation. Next‐generation sequencing identified an in‐frame fusion between MAZ exon 3 on chromosome 16 and NCOA2 exon 12 on chromosome 8. Fluorescence in situ hybridization (FISH) confirmed a break‐apart signal at the NCOA2 locus. To the best of our knowledge, this represents the first documented instance of an NCOA2 rearrangement involving MAZ in SRCSs. This case broadens the molecular spectrum of SRCSs, highlights the importance of incorporating molecular techniques into diagnostic workflows, and may have implications for future diagnostic and therapeutic strategies.