DEK::AFF2 Fusion-Associated Sinonasal Carcinoma With Intracranial and Orbital Involvement.

Abstract

Sinonasal carcinomas encompass a molecularly heterogeneous group of malignancies. DEK::AFF2 fusion-associated carcinoma is a recently recognized subtype of nonkeratinizing squamous cell carcinoma characterized by deceptively bland morphology yet clinically aggressive behavior. We report the case of a 67-year-old woman who presented with a rapidly enlarging sinonasal mass with extensive local invasion involving both the intracranial compartment and orbit. Histologically, the tumor was composed of cytologically bland cells with monotonous nuclei and exhibited a combination of exophytic and endophytic growth patterns that closely mimicked a sinonasal papilloma. Although the tumor shows predominantly squamous differentiation, focal extracellular mucin was also present. The brain-invasive foci demonstrated tumor cells in sheets and nests floating within pools of mucin, a pattern focally reminiscent of mucinous adenocarcinoma. RNA sequencing identified a DEK::AFF2 fusion with breakpoints at DEK exon 7 and AFF2 exon 6, confirming the diagnosis. The tumor demonstrated positive PD-L1 expression with a combined positive score (CPS) of 40 and a low tumor mutational burden (TMB) of 0.5 mutations/Mb. This case highlights the diagnostic challenges posed by DEK::AFF2 fusion-associated carcinoma, underscores the importance of molecular profiling for accurate classification, and demonstrates the aggressive clinical behavior of this rare entity.