Since the first description of sinonasal undifferentiated carcinoma (SNUC) as a distinctive highly aggressive sinonasal neoplasm with probable origin from the sinonasal mucosa (Schneiderian epithelium), SNUC has been the subject of ongoing study and controversy. In particular, the SNUC category gradually became a "wastebasket" for any undifferentiated or unclassifiable sinonasal malignancy of definite or probable epithelial origin. However, with the availability of more specific and sensitive immunohistochemical antibodies and increasing implementation of novel genetic tools, the historical SNUC category became the subject of progressive subdivision leading to recognition of specific genetically defined, reproducible subtypes. These recently recognized entities are characterized by distinctive genetic aberrations including NUTM1-rearranged carcinoma (NUT carcinoma) and carcinomas associated with inactivation of different members of the SWI/SNF chromatin-remodeling gene complex such as SMARCB1-deficient and less frequently SMARCA4-deficient carcinoma. The ring became almost closed, with recent studies highlighting frequent oncogenic IDH2 mutations in the vast majority of histologically defined SNUCs, with a frequency of 82%. A review of these cases suggests the possibility that "true SNUC" probably represents a distinctive neoplastic disease entity, morphologically, phenotypically, and genetically. This review addresses this topic from a historical perspective, with a focus on recently recognized genetically defined subsets within the SNUC spectrum.

Alpert Medical School at Brown University Providence RI

Audiology Rigshospitalet Copenhagen Denmark

Department of Pathology Charles University Faculty of Medicine in Plzen Plzen Czech Republic

Department of Pathology Liverpool Clinical Laboratories Royal Liverpool University Hospital

Department of Pathology Southern California Permanente Medical Group Woodland Hills CA

Department of Pathology University of Texas Southwestern Medical Center Dallas TX

Department of Translational Research School of Medicine University of Pisa Pisa

Departments of Pathology

Epigenetics and Human Disease Laboratory Department of Biomedical Sciences and Medicine University of Algarve Faro Portugal

Institute of Pathology Friedrich Alexander University Erlangen Nürnberg University Hospital Erlangen Germany

International Head and Neck Scientific Group Padua Italy

Otolaryngology Head and Neck Surgery

Royal National Throat Nose and Ear Hospital University College London Hospitals London

School of Dentistry University of Liverpool Liverpool UK

University of Udine School of Medicine Udine

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Sinonasal malignancy: ESMO-EURACAN Clinical Practice Guideline for diagnosis, treatment and follow-up

SMARCB1-deficient sinonasal adenocarcinoma: a rare variant of SWI/SNF-deficient malignancy often misclassified as high-grade non-intestinal-type sinonasal adenocarcinoma or myoepithelial carcinoma