AFF2 (AF4/FMR2 family member 2)

It is essential to be able to identify these entities, as they have distinct profiles in terms of progression and prognosis compared to other sinonasal tumors. The present study exhaustively describes their clinical and pathologic characteristics.

Recognition of recurrent diagnostic pitfalls, combined with a systematic pattern-based approach and judicious use of ancillary studies, is essential for accurate classification. Integration of morphologic, immunophenotypic, and molecular findings helps avoid misdiagnosis and ensures appropriate patient management.

Viral and targeted molecular testing are critical to classification of these tumors. "So it's squamous" is no longer the end of the work up-it is the beginning of a more refined classification.

The patient underwent chemotherapy with epirubicin and ifosfamide but experienced recurrence with lymph node and peritoneal involvement and succumbed to the disease after 9 months. Moreover, it identifies a novel fusion, which may have implications for tumor classification and diagnostic refinement. The morphological findings also suggest a possible association with poor clinical outcomes.

Combined surgical and radiation therapy lead to adequate response. Accurate diagnosis requires a multidisciplinary approach due to its challenging and rare presentation, particularly in an atypical age group.

Subsequent treatment with paclitaxel plus cetuximab also led to disease progression after two months...Third-line therapy with 5-FU, carboplatin, and pembrolizumab achieved a partial response, but disease progression occurred after nine months...Additionally, acquired MYC amplification may contribute to resistance to chemotherapy and pembrolizumab. These findings underscore the importance of personalized treatment strategies in SCC patients with specific genomic alterations.

DEK::AFF2 carcinoma appears to exhibit three key biological features favoring aerogenous dissemination: anatomic location of the primary tumor, loss of intercellular adhesion, and strong affinity for ciliated respiratory epithelium. These cases may help enhance our understanding of aerogenous tumor cell spread, including phenomena such as spread through air spaces (STAS).

While the DEK::AFF2 fusion is well-characterized in sinonasal region tumors, alternate fusion partners are becoming increasingly recognized.

The patient demonstrated an exceptional response to three cycles of neoadjuvant gemcitabine and cisplatin, achieving complete remission on MRI restaging. These cases highlight the aggressive nature of DEK::AFF2 fusion-associated carcinomas and the critical role of genetic profiling in diagnosis and management. The exceptional, first ever reported response to neoadjuvant chemotherapy in one case underscores the potential for personalized treatment strategies, warranting further investigation into targeted therapies for this rare malignancy.

These findings suggest that AFF2-rearranged tumors form a spectrum of carcinomas with diverse morphologies, immunophenotypes, and differentiation patterns. Given the consistent involvement of the AFF2 gene and uniform AFF2 immunohistochemical positivity despite morphological heterogeneity, we propose naming this entity AFF2 carcinoma.