A potential conundrum in dermatopathology: molecularly confirmed superficial ossifying fibromyxoid tumors with unusual histomorphologic findings and a novel fusion.

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain histogenesis, primarily arising in subcutaneous tissues of the extremities, head and neck, or trunk. Most cases present as well-circumscribed masses with a characteristic morphologic appearance, comprising cytologically bland ovoid cells with fibromyxoid stroma, a peripheral rim of metaplastic bone, and lobulated architecture. Nevertheless, tumors displaying unusual morphologic characteristics pose significant diagnostic challenges, requiring the detection of a pathogenic fusion for a definitive diagnosis. The majority of OFMTs exhibits PHF1 gene rearrangements. Herein, we present six cases of molecularly confirmed OFMTs with uncommon histomorphologic features, including the absence of myxoid stroma, extensive chondroid differentiation, prominent clear cell morphology, collagen entrapment, interdigitating fibrocollagenous and fibromyxoid stromal elements, and conspicuous red blood cell extravasation. One case harbored a novel fusion (EPC1::SUZ12). This study emphasizes the broad range of morphologic manifestations that can be encountered in OFMT and the crucial role of molecular testing in establishing a conclusive diagnosis in such cases.