130 Ossifying Fibromyxoid Tumor Featuring a Novel NBPF10::PHF1 Fusion

Introduction/Objective Ossifying fibromyxoid tumor (OFMT) represents a rare mesenchymal neoplasm of uncertain differentiation which harbors PHF1 fusion with various partner genes, notably EP400, MEAF6, EPC1, and TFE3. Herein we report a case of OFMT with a novel NBPF10::PHF1 fusion. Methods/Case Report The patient is a 41-year-old female who presented initially for evaluation of subarachnoid hemorrhage secondary to a ruptured cerebral aneurysm. Incidentally, imaging identified a 2.8 cm heterogeneously calcified mass in the left supraclavicular region. Biopsy of this mass demonstrated spindled to ovoid cells within a variably myxoid and densely collagenous stroma, lacking classic bone formation and typical lobular architecture. The lesion exhibited prominent staghorn vessels and minimal cytologic pleomorphism. Immunohistochemical staining revealed diffuse CD10 positivity, focal desmin positivity, and cytoplasmic localization of beta-catenin, while markers such as S100, MUC4, SMA, SOX10, CD34, STAT6, and TLE1 were negative. Mayo Clinic Sarcoma targeted gene fusion/rearrangement next-generation sequencing panel (SARCP) was performed and identified an NBPF10::PHF1 fusion, confirming the diagnosis of OFMT. Results NA Conclusion This case expands the spectrum of PHF1 gene fusion partners in OFMT. It highlights metaplastic bone is not always present in OFMT, especially in small biopsies, and underscores the importance of molecular testing in diagnosing this rare mesenchymal neoplasm.