Nodular fasciitis (NF) is a benign proliferation of fibroblasts and myofibroblasts occurring most commonly in the upper extremities that can mimic a variety of mesenchymal tumors including sarcoma. Although reported in almost all anatomic locations, only 7 cases of intraneural nodular fasciitis have been reported in English literature. The CTNNB1::USP6 gene fusion has not been previously reported in intraneural nodular fasciitis, although it has been reported in three entities including aneurysmal bone cyst, nodular fasciitis, and intravascular fasciitis. We report a case of a 29-year-old female with a 6-month history of left leg weakness, myalgia, and paresthesia of the left foot prompting a clinical diagnosis of a peripheral nerve sheath tumor. Surgical resection was performed, and histologic sections revealed a circumscribed lesion composed of banal spindle cells with variable interstitial collagen and occasional mitotic figures. By immunohistochemistry, the lesional cells were positive for smooth muscle actin, smooth muscle heavy chain myosin, p16, and H-caldesmon and negative for desmin, S-100, SOX10, HMB45, CD34, and beta-catenin. Fluorescence in Situ Hybridization for USP6 gene rearrangement was positive and consistent with the diagnosis of nodular fasciitis. Next-generation sequencing uncovered the presence of a CTNNB1::USP6 gene fusion involving CTNNB1 gene in exon 1 at the genomic position chr3:41241161 and the USP6 gene in exon 1 at the genomic position chr17:5033231. This gene fusion was confirmed by Sanger sequencing. Herein, we report a case that underscores the rare incidence of intraneural nodular fasciitis and highlights the pitfalls associated with the clinical differential diagnoses of intraneural tumors.
Keywords: CTNNB1::USP6; intraneural localization; molecular genetics; nodular fasciitis; pseudosarcoma.