Ossification-deficient atypical ossifying fibromyxoid tumor of submandibular gland with PHF1::EP400 fusion: diagnostic challenges.

Abstract

Background: Ossifying fibromyxoid tumor (OFMT) is a soft tissue neoplasm of uncertain differentiation, characterized by peripheral ossification within a fibromyxoid stroma and typically occurring in the extremities and trunk. However, OFMT arising from the submandibular gland is extremely rare.

Case presentation: A 40-year-old male presented with a progressively enlarging painless mass in the left submandibular region over two years. Radiological examination revealed a well-demarcated, round lesion measuring 1.3 cm in maximal diameter. Histopathology demonstrated nodular/lobular growth of uniform round-to-oval tumor cells with abundant eosinophilic cytoplasm, focal epithelioid features, and minimal atypia. Prominent myxoid stroma containing vascular networks was also observed in tumor. While peripheral infiltration was noted in small nests, resection margins were clear and perineural invasion absent. Immunohistochemistry showed diffuse S-100/vimentin positivity, focal weak desmin reactivity, and cytokeratin/CD34/SMA negativity. Next-generation sequencing (NGS) identified a pathogenic PHF1::EP400 fusion, confirming OFMT diagnosis despite absent calcification. The presence of infiltrative tumor cell growth warrants a diagnosis of atypical OFMT in this case. No recurrence occurred at 18-month follow-up.

Conclusion: In this report, we present a rare case of OFMT arising in the submandibular region without histological evidence of ossification. This case give prominence to molecular detection in diagnosing morphologically ambiguous tumors and expands the clinicopathological spectrum of OFMT regarding anatomical distribution and histological variants.