{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:47:51Z","timestamp":1791301671701,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:p>Olfactory carcinoma is one of many names applied to sinonasal malignancies with histologic similarity to olfactory neuroblastoma (ONB) but cytokeratin expression or gland formation. It is unclear whether these neuroepithelial tumors represent a unified category and if they are separate from ONB and currently-recognized sinonasal carcinomas. This study aims to explore their clinicopathologic characteristics based on a large collective experience. A total of 53 sinonasal tumors with neuroepithelial differentiation were identified affecting 41 men and 12 women, median age 47 years (range: 12 to 82\u2009y). The vast majority arose in the superior nasal cavity and presented at the high Kadish-Morita stage. Frequent histologic findings included (1) lobulated and solid growth, (2) rosettes and\/or neurofibrillary stroma, (3) high-grade cytology, (4) complex, often ciliated glands, (5) nonfocal pancytokeratin expression, (6) neuroendocrine pos+itivity, and (7) variable S100-positive sustentacular cells. Twelve patients with available follow-up (48%) developed progressive disease at a median 8 months (range: 0 to 114\u2009mo to progression), and 7 (28%) died of disease. Despite disparate historical terminology, neuroepithelial differentiation is a recurrent and recognizable histologic pattern that is associated with aggressive behavior in sinonasal tumors. While tumors with this phenotype may originate from olfactory mucosa, well-developed epithelial features warrant separation from conventional ONB and neural elements distinguish them from most sinonasal carcinomas. Although their full histogenesis remains uncertain and some heterogeneity may exist, we propose that this pattern is sufficiently distinctive to merit separate recognition as olfactory carcinoma. Use of consistent nomenclature may facilitate greater recognition of tumors with this phenotype and understanding of their pathogenesis and classification.<\/jats:p>","DOI":"10.1097\/pas.0000000000001908","type":"journal-article","created":{"date-parts":[[2022,4,14]],"date-time":"2022-04-14T11:01:48Z","timestamp":1649934108000},"page":"1025-1035","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["Sinonasal Tumors With Neuroepithelial Differentiation (Olfactory Carcinoma)"],"prefix":"10.1097","volume":"46","author":[{"given":"Lisa M.","family":"Rooper","sequence":"first","affiliation":[{"name":"Pathology"},{"name":"Oncology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin A.","family":"Bishop","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Faquin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Foss","sequence":"additional","affiliation":[{"name":"Dermatology"},{"name":"Head & Neck Pathology, Joint Pathology Center, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary L.","family":"Gallia","sequence":"additional","affiliation":[{"name":"Oncology"},{"name":"Otolaryngology\u2014Head and Neck Surgery"},{"name":"Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vickie Y.","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James S.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Pathology, Microbiology, and Immunology"},{"name":"Otolaryngology\u2014Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiya","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward B.","family":"Stelow","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Virginia, Charlottesville, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lester D.R.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Head and Neck Pathology Consultations, Woodland Hills, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce M.","family":"Wenig","sequence":"additional","affiliation":[{"name":"Department of Pathology, Moffitt Cancer Center, Tampa, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William H.","family":"Westra","sequence":"additional","affiliation":[{"name":"Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,4,15]]},"reference":[{"key":"R4-20250608","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.oraloncology.2017.09.010","article-title":"The clinicopathological spectrum of olfactory neuroblastoma and sinonasal neuroendocrine neoplasms: Refinements in diagnostic criteria and impact of multimodal treatments on survival","volume":"74","author":"Turri-Zanoni","year":"2017","journal-title":"Oral Oncol"},{"key":"R5-20250608","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s12105-007-0004-7","article-title":"Non-small cell neuroendocrine carcinoma of the sinonasal tract and nasopharynx. Report of 2 cases and review of the literature","volume":"1","author":"Weinreb","year":"2007","journal-title":"Head Neck Pathol"},{"issue":"suppl 1","key":"R6-20250608","first-page":"E2259","article-title":"Neuroendocrine neoplasms of the sinonasal region","volume":"38","author":"Bell","year":"2016","journal-title":"Head Neck"},{"key":"R7-20250608","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/s12105-016-0696-7","article-title":"Neuroendocrine neoplasms of the sinonasal tract: neuroendocrine carcinomas and olfactory neuroblastoma","volume":"10","author":"Shah","year":"2016","journal-title":"Head Neck Pathol"},{"key":"R8-20250608","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1093\/ajcp\/94.5.547","article-title":"Olfactory neuroblastoma. Additional immunohistochemical characterization","volume":"94","author":"Frierson","year":"1990","journal-title":"Am J Clin Pathol"},{"key":"R9-20250608","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.ejca.2012.12.008","article-title":"Low- and high-grade esthesioneuroblastomas display a distinct natural history and outcome","volume":"49","author":"Malouf","year":"2013","journal-title":"Eur J Cancer"},{"key":"R10-20250608","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/00000478-199804000-00002","article-title":"Olfactory neuroblastoma is not related to the Ewing family of tumors: absence of EWS\/FLI1 gene fusion and MIC2 expression","volume":"22","author":"Argani","year":"1998","journal-title":"Am J Surg Pathol"},{"key":"R11-20250608","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/ajcp\/88.2.139","article-title":"Esthesioneuroblastoma. Intermediate filaments, neuroendocrine, and tissue-specific antigens","volume":"88","author":"Axe","year":"1987","journal-title":"Am J Clin Pathol"},{"key":"R12-20250608","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s10014-012-0083-3","article-title":"Clincopathological analysis of olfactory neuroblastoma","volume":"29","author":"Fukushima","year":"2012","journal-title":"Brain Tumor Pathol"},{"key":"R13-20250608","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/1097-0142(19950701)76:1<4::AID-CNCR2820760103>3.0.CO;2-E","article-title":"Olfactory neuroblastoma. An immunohistochemical, ultrastructural, and flow cytometric study","volume":"76","author":"Hirose","year":"1995","journal-title":"Cancer"},{"key":"R14-20250608","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1097\/00000478-198610000-00004","article-title":"The spectrum of olfactory neural tumors. A light-microscopic immunohistochemical and ultrastructural analysis","volume":"10","author":"Taxy","year":"1986","journal-title":"Am J Surg Pathol"},{"key":"R15-20250608","first-page":"616","article-title":"Immunohistochemical diagnosis of sinonasal melanoma, carcinoma, and neuroblastoma with monoclonal antibodies HMB-45 and anti-synaptophysin","volume":"112","author":"Wick","year":"1988","journal-title":"Arch Pathol Lab Med"},{"key":"R16-20250608","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/modpathol.3880522","article-title":"Neuroectodermal neoplasms of the head and neck with emphasis on neuroendocrine carcinomas","volume":"15","author":"Mills","year":"2002","journal-title":"Mod Pathol"},{"key":"R17-20250608","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1097\/PAS.0000000000001697","article-title":"IDH2 R172 mutations across poorly differentiated sinonasal tract malignancies: forty molecularly homogenous and histologically variable cases with favorable outcome","volume":"45","author":"Gloss","year":"2021","journal-title":"Am J Surg Pathol"},{"key":"R18-20250608","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1038\/s41379-019-0285-x","article-title":"DNA methylation-based classification of sinonasal undifferentiated carcinoma","volume":"32","author":"Dogan","year":"2019","journal-title":"Mod Pathol"},{"key":"R19-20250608","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/modpathol.2016.239","article-title":"Recurrent IDH2 R172X mutations in sinonasal undifferentiated carcinoma","volume":"30","author":"Jo","year":"2017","journal-title":"Mod Pathol"},{"key":"R20-20250608","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1002\/path.4915","article-title":"Frequent IDH2 R172 mutations in undifferentiated and poorly-differentiated sinonasal carcinomas","volume":"242","author":"Dogan","year":"2017","journal-title":"J Pathol"},{"key":"R21-20250608","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1097\/PAS.0000000000001428","article-title":"SMARCA4-deficient sinonasal carcinoma: a series of 10 cases expanding the genetic spectrum of SWI\/SNF-driven sinonasal malignancies","volume":"44","author":"Agaimy","year":"2020","journal-title":"Am J Surg Pathol"},{"key":"R22-20250608","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1007\/s12105-017-0783-4","article-title":"SMARCA4-deficient sinonasal carcinoma","volume":"11","author":"Agaimy","year":"2017","journal-title":"Head Neck Pathol"},{"key":"R23-20250608","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1097\/PAS.0000000000001508","article-title":"Recurrent loss of SMARCA4 in sinonasal teratocarcinosarcoma","volume":"44","author":"Rooper","year":"2020","journal-title":"Am J Surg Pathol"},{"key":"R24-20250608","first-page":"229A","article-title":"Olfactory neuroblastoma with divergent differentiation: from ganglioneuroblastoma to carcinoma","volume":"20","author":"Seethala","year":"2007","journal-title":"Mod Pathol"},{"key":"R26-20250608","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1080\/01676830.2016.1193537","article-title":"Aggressive esthesioneuroblastoma with divergent differentiation: a taxonomic dilemma","volume":"35","author":"Charles","year":"2016","journal-title":"Orbit"},{"key":"R27-20250608","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s12105-017-0781-6","article-title":"Olfactory neuroblastoma with divergent differentiation: an unusual histologic finding in a rare tumor","volume":"11","author":"Meyer","year":"2017","journal-title":"Head Neck Pathol"},{"key":"R28-20250608","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1046\/j.1440-1827.2001.01300.x","article-title":"Olfactory neuroblastoma with epithelial and endocrine differentiation transformed into ganglioneuroma after chemoradiotherapy","volume":"51","author":"Miura","year":"2001","journal-title":"Pathol Int"},{"key":"R29-20250608","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/neup.12730","article-title":"Olfactory neuroblastoma associated with extensive \u201cin situ\u201d lesion and aberrant glandular and rhabdomyosarcomatous differentiation","volume":"41","author":"Shintaku","year":"2021","journal-title":"Neuropathology"},{"key":"R30-20250608","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1007\/s12105-019-01062-w","article-title":"Mixed olfactory neuroblastoma and adenocarcinoma with in situ neuroendocrine hyperplasia","volume":"14","author":"Attwood","year":"2020","journal-title":"Head Neck Pathol"},{"key":"R31-20250608","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4103\/sni.sni_30_17","article-title":"A rare case report of mixed olfactory neuroblastoma: carcinoma with review of literature","volume":"8","author":"Gandhoke","year":"2017","journal-title":"Surg Neurol Int"},{"key":"R32-20250608","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1002\/1097-0142(19841101)54:9<2019::AID-CNCR2820540940>3.0.CO;2-P","article-title":"Mixed olfactory neuroblastoma and carcinoma. A report of two cases","volume":"54","author":"Miller","year":"1984","journal-title":"Cancer"},{"key":"R33-20250608","doi-asserted-by":"crossref","first-page":"97","DOI":"10.25259\/SNI_473_2019","article-title":"Mixed olfactory neuroblastoma and neuroendocrine carcinoma: an unusual case report and literature review","volume":"11","author":"Lao","year":"2020","journal-title":"Surg Neurol Int"},{"key":"R34-20250608","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/BF00691536","article-title":"Esthesioneuroepithelioma, a true neurosensorial tumor. Light- and electron-microscopic study of a case with endocranial extension","volume":"55","author":"Hassoun","year":"1981","journal-title":"Acta Neuropathol"},{"key":"R35-20250608","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1111\/j.1440-1789.2006.00703.x","article-title":"Olfactory neuroepithelioma: an immunohistochemical and ultrastructural study","volume":"26","author":"Sugita","year":"2006","journal-title":"Neuropathology"},{"key":"R36-20250608","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/BF00687075","article-title":"Esthesioneuroepithelioma: a tumor of true olfactory epithelium origin. An ultrastructural and immunohistochemical study","volume":"75","author":"Takahashi","year":"1987","journal-title":"Acta Neuropathol"},{"key":"R37-20250608","first-page":"7","article-title":"Olfactory neuroepithelioma arising from the olfactory placode","volume":"19","author":"Utsuki","year":"2000","journal-title":"Clin Neuropathol"},{"key":"R38-20250608","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1097\/PAP.0b013e3181e3bf80","article-title":"Adenocarcinoma of the upper aerodigestive tract","volume":"17","author":"Stelow","year":"2010","journal-title":"Adv Anat Pathol"},{"key":"R39-20250608","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1046\/j.1365-2559.1997.d01-615.x","article-title":"Mixed olfactory neuroblastoma and craniopharyngioma: an unusual pathological finding","volume":"30","author":"Chang","year":"1997","journal-title":"Histopathology"},{"key":"R40-20250608","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1227\/00006123-199305000-00002","article-title":"Esthesioneuroblastoma: prognosis and management","volume":"32","author":"Morita","year":"1993","journal-title":"Neurosurgery"},{"key":"R42-20250608","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s12105-018-0887-5","article-title":"Sinonasal neuroendocrine neoplasms: current challenges and advances in diagnosis and treatment, with a focus on olfactory neuroblastoma","volume":"12","author":"Bell","year":"2018","journal-title":"Head Neck Pathol"},{"key":"R43-20250608","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/S0046-8177(98)90452-X","article-title":"Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses","volume":"29","author":"Perez-Ordonez","year":"1998","journal-title":"Hum Pathol"},{"key":"R44-20250608","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1097\/PAS.0000000000000521","article-title":"Ciliated HPV-related carcinoma: a well-differentiated form of head and neck carcinoma that can be mistaken for a benign cyst","volume":"39","author":"Bishop","year":"2015","journal-title":"Am J Surg Pathol"},{"key":"R45-20250608","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/PAS.0000000000000932","article-title":"MAML2 rearrangements in variant forms of mucoepidermoid carcinoma: ancillary diagnostic testing for the ciliated and warthin-like variants","volume":"42","author":"Bishop","year":"2018","journal-title":"Am J Surg Pathol"},{"key":"R46-20250608","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s12105-015-0653-x","article-title":"Ciliated adenosquamous carcinoma: expanding the phenotypic diversity of human papillomavirus-associated tumors","volume":"10","author":"Radkay-Gonzalez","year":"2016","journal-title":"Head Neck Pathol"},{"key":"R47-20250608","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00401-018-1854-7","article-title":"DNA methylation-based reclassification of olfactory neuroblastoma","volume":"136","author":"Capper","year":"2018","journal-title":"Acta Neuropathol"},{"key":"R48-20250608","doi-asserted-by":"crossref","first-page":"811.e5","DOI":"10.1016\/j.celrep.2018.09.047","article-title":"Integrated multi-omic analysis of esthesioneuroblastomas identifies two subgroups linked to cell ontogeny","volume":"25","author":"Classe","year":"2018","journal-title":"Cell Rep"}],"container-title":["American Journal of Surgical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/PAS.0000000000001908","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,8]],"date-time":"2025-06-08T17:03:20Z","timestamp":1749402200000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/PAS.0000000000001908"}},"subtitle":["Delineation of Their Pathologic and Clinical Features With Insights into Their Relationship to Olfactory Neuroblastoma and Sinonasal Carcinoma"],"short-title":[],"issued":{"date-parts":[[2022,4,15]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022]]}},"URL":"https:\/\/doi.org\/10.1097\/pas.0000000000001908","relation":{},"ISSN":["0147-5185"],"issn-type":[{"value":"0147-5185","type":"print"}],"subject":[],"published":{"date-parts":[[2022,4,15]]}}}