An Examination of the Diagnostic Utility of Ubiquitin-Specific Peptidase 6 (USP6) Rearrangement in Differentiating Nodular Fasciitis From Inflammatory Myofibroblastic Tumor: A Case Report.

Nodular fasciitis (NF) is a benign yet diagnostically challenging mesenchymal myofibroblastic proliferation that often mimics the histological features of inflammatory myofibroblastic tumors (IMTs) and soft tissue sarcomas. The overlap in histopathological appearance, compounded by the variability in immunohistochemical (IHC) staining, frequently leads to diagnostic uncertainty. In this report, we present a case of a rapidly expanding lesion on the left medial mandible, ultimately diagnosed as NF. Molecular analysis through fluorescence in situ hybridization (FISH) identified a ubiquitin-specific peptidase 6 (USP6; 17p13.2) gene rearrangement, a distinctive marker of NF, which played a critical role in confirming the diagnosis. IHC analysis, including negative staining for cytokeratin and ALK, further helped differentiate this benign entity from other IMTs and malignancies, highlighting the importance of combining molecular diagnostics with traditional histopathological techniques to ensure accurate classification and avoid misdiagnosis.