Primary Laryngeal Squamous Cell Carcinoma with DEK::AFF2 Fusion: The First Case Report

DEK::AFF2 fusion squamous cell carcinoma (SCC) is a rare and aggressive subtype of non-keratinizing SCC. Previously reported cases have predominantly involved the sinonasal tract, middle ear, and skull base. To date, only 62 cases have been described, with rare exceptions including a primary lung tumor and a recurrent tumor in the trachea.

We describe the first documented case of primary laryngeal SCC harboring a DEK::AFF2 fusion in a 64-year-old female who presented with progressive hoarseness and airway obstruction. Clinical, radiologic, histopathologic, immunohistochemical, and molecular analyses were performed to characterize the tumor.

Imaging and laryngoscopic evaluation revealed a transglottic mass. Histopathology demonstrated non-keratinizing SCC composed of monotonous tumor cells with an infiltrative growth pattern. Immunohistochemistry showed diffuse p40 positivity and moderate to strong nuclear AFF2 expression. The DEK::AFF2 fusion was confirmed by fluorescence in situ hybridization and reverse transcription polymerase chain reaction. The patient underwent total laryngectomy followed by adjuvant chemoradiotherapy and remains disease-free at 12 months of follow-up.

This case expands the known anatomical distribution of DEK::AFF2 fusion SCC to include the larynx, suggesting that this rare entity may arise throughout the respiratory tract epithelium. Recognition of this fusion is important in the differential diagnosis of non-keratinizing SCCs across the respiratory tract.