DEK::AFF2 Fusion-Associated Nonkeratinizing Squamous Cell Carcinoma with Noncontiguous Middle Ear and Sinonasal...

Area of Science:

• Oncology
• Pathology
• Genetics

Background:

• DEK::AFF2 fusion-associated nonkeratinizing squamous cell carcinoma (NSCC) is a rare, HPV-independent malignancy.
• This entity often presents with subtle morphologic features, mimicking benign or inflammatory conditions.
• Accurate diagnosis is challenging due to its deceptive appearance.

Purpose of the Study:

• To report a case of DEK::AFF2 fusion-associated NSCC involving noncontiguous middle ear and sinonasal sites.
• To detail the clinicopathologic, immunophenotypic, and molecular characteristics of this rare tumor.
• To emphasize the importance of recognizing this entity to prevent misdiagnosis.

Main Methods:

• Case presentation of a 21-year-old female with recurrent otorrhea and hearing loss.
• Radiologic imaging revealed noncontiguous lesions in the middle ear/mastoid and sinonasal regions.
• Histopathological examination, immunohistochemistry (CK5/6, p40, p53, p16, INSM1, AFF2), and targeted next-generation sequencing were performed.

Main Results:

• Both lesions exhibited nonkeratinizing squamous proliferation with focal papillary/inverted architecture, mild atypia, and stromal invasion.
• Immunohistochemistry showed diffuse nuclear AFF2, CK5/6+, p40+, wild-type p53, p16-, and INSM1-.
• DEK::AFF2 fusion was confirmed in both tumor sites via next-generation sequencing.

Conclusions:

• This case expands the known anatomical distribution of DEK::AFF2 fusion-associated NSCC to include the middle ear and sinonasal regions.
• The findings underscore the need for a high index of suspicion for this entity in relevant clinical scenarios.
• Comprehensive evaluation including molecular testing is essential for definitive diagnosis and appropriate management.