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Adv Anat Pathol. 2020 Mar;27(2):51-60. doi: 10.1097/PAP.0000000000000258.

Sinonasal Undifferentiated Carcinoma (SNUC): From an Entity to Morphologic Pattern and Back Again-A Historical Perspective.

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Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Erlangen, Germany.
Department of Translational Research, School of Medicine, University of Pisa, Pisa.
Royal National Throat, Nose and Ear Hospital, University College London Hospitals, London.
Department of Pathology, Charles University, Faculty of Medicine in Plzen, Plzen, Czech Republic.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX.
Department of Pathology, Liverpool Clinical Laboratories, Royal Liverpool University Hospital.
School of Dentistry, University of Liverpool, Liverpool, UK.
Departments of Pathology.
Otolaryngology Head and Neck Surgery.
Audiology, Rigshospitalet, Copenhagen, Denmark.
Alpert Medical School at Brown University, Providence, RI.
Epigenetics and Human Disease Laboratory, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal.
Department of Pathology, Southern California Permanente Medical Group, Woodland Hills, CA.
University of Udine School of Medicine, Udine.
International Head and Neck Scientific Group, Padua, Italy.


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.

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