Nontraumatic Myositis Ossificans Adjacent to the Femoral Nerve: A Ubiquitin-Specific Peptidase 6 (USP6)-Rearranged Lesion Mimicking Malignancy.

Myositis ossificans (MO) is a benign, self-limiting lesion characterized by heterotopic ossification that can mimic malignancy both radiographically and histologically. Non-traumatic MO is particularly challenging to diagnose, especially when arising adjacent to major neurovascular structures. Recent studies have identified ubiquitin-specific peptidase 6 (USP6) gene rearrangements in a subset of MO, linking it to a family of transient fibroblastic/myofibroblastic neoplasms. We present a 21-year-old female who presented with progressive right lower extremity pain and weakness without a history of trauma. Imaging revealed an intramuscular thigh mass adjacent to the femoral nerve, raising concern for a peripheral nerve sheath tumor or malignancy. Due to worsening symptoms and diagnostic uncertainty, the patient underwent surgical resection with femoral nerve neuroplasty. Histopathological analysis demonstrated a spindle cell lesion with zonal ossification, and fluorescence in situ hybridization confirmed a USP6 gene rearrangement, establishing the diagnosis of non-traumatic MO. Postoperatively, the patient experienced improvement in strength and partial sensory recovery. Non-traumatic MO can closely mimic peripheral nerve sheath tumors when arising adjacent to major nerves, creating significant diagnostic uncertainty. This case highlights the importance of integrating imaging features, histology, and molecular confirmation of USP6 rearrangement to accurately distinguish benign pseudosarcomatous lesions from malignancy and guide appropriate management.