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Novel MEAF6‐SUZ12 fusion in ossifying fibromyxoid tumor with unusual features

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation that has the capacity for local recurrence and metastasis. Many OFMTs, including typical, atypical, and malignant tumors, have demonstrated recurrent gene fusions. The fusion partners reported to date share a common core function in that they play either a direct or indirect role in processes influencing histone modification. Herein, we report an OFMT with unusual morphology and non‐specific immunoprofile harboring a novel MEAF6‐SUZ12 fusion. A 34‐year‐old male presented with a slowly growing mass in the right antecubital fossa. Excision demonstrated a 6.9 cm partially encapsulated, tan‐white, lobulated, and calcified lesion. Microscopic evaluation demonstrated cytologically bland spindle to ovoid cells arranged in a haphazard manner within a fibromyxoid background containing dense collagen, often with sclerotic nodules, and randomly distributed ossification. The tumor cells were diffusely positive for CD34 while essentially negative for S100, desmin, MUC4, SOX10, AE1/3, SMA, and EMA. Next‐generation sequencing studies (sarcoma gene fusion next‐generation sequencing panel with subsequent Sanger confirmation) performed on formalin‐fixed paraffin‐embedded tissue detected a fusion product between MEAF6 exon 4 (NM_001270875) and SUZ12 exon 2 (NM_001321207.1). The proposed mechanism of pathogenesis in OFMT, namely epigenetic dysregulation, is reinforced by the fact that both of these partner genes are involved in histone modification.