DEK::AFF2 Fusion Sinonasal Tract and Skull Base Nonkeratinizing Squamous Cell Carcinoma

DEK::AFF2 fusion‑positive sinonasal tract and skull base nonkeratinizing squamous cell carcinoma (DEK::AFF2 SCC) is a rare and recently recognized entity; however, its clinicopathologic and demographic features remain incompletely defined. We aimed to further refine and supplement the characterization of this entity. We retrieved institutional pathology records and identified 50 DEK::AFF2 SCCs at a single institution (2009-2025). The cohort included 20 males and 30 females aged 18-74 years (median, 50.5 y). The most common presenting symptoms were nasal obstruction and epistaxis. The predominant primary site was the paranasal sinus, followed by the nasal cavity and nasopharynx. Histologically, most tumors exhibit mixed exophytic and endophytic growth patterns, complex anastomosing trabeculae, monotonous cytomorphology, acantholytic changes, and tumor-infiltrating neutrophils. High-grade histologic features and infiltration were observed in 24% of the cases; 6% presented features resembling mucoepidermoid carcinoma, and 4% presented an ameloblastoma-like appearance. Immunohistochemically, more than 70% of the cases coexpressed squamous and glandular markers. The recurrence rate was 59.2%, the lymph node metastasis rate was 24.5%, the distant metastasis rate was 20.4%, and the disease‑related mortality rate was 24.5%, with a median follow-up period of 71 months (range, 5-235 mo). This study expanded the histologic spectrum of DEK::AFF2 SCC and demonstrated its aggressive behavior, highlighting the need for accurate differentiation from mimics and long‑term surveillance.