Original ArticlesSinonasal Tumors With Neuroepithelial Differentiation (Olfactory Carcinoma) Delineation of Their Pathologic and Clinical Features With Insights into Their Relationship to Olfactory Neuroblastoma and Sinonasal CarcinomaRooper, Lisa M. MD*,†; Bishop, Justin A. MD‡; Faquin, William C. MD, PhD§; Foss, Robert D. DDS∥,¶; Gallia, Gary L. MD, PhD†,#,**; Jo, Vickie Y. MD††; Lewis, James S. Jr MD‡‡,§§; Nishino, Michiya MD, PhD∥∥; Stelow, Edward B. MD¶¶; Thompson, Lester D.R. MD##; Wenig, Bruce M. MD***; Westra, William H. MD††† Author Information Departments of *Pathology †Oncology ∥Dermatology **Otolaryngology—Head and Neck Surgery #Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD ‡Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX §Department of Pathology, Massachusetts General Hospital and Harvard Medical School ††Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School ∥∥Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA ¶Head & Neck Pathology, Joint Pathology Center, Silver Spring, MD Departments of ‡‡Pathology, Microbiology, and Immunology §§Otolaryngology—Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, TN ¶¶Department of Pathology, University of Virginia, Charlottesville, VA ##Head and Neck Pathology Consultations, Woodland Hills, CA ***Department of Pathology, Moffitt Cancer Center, Tampa, FL †††Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY W.H.W. is co-corresponding author. A portion of this data was presented in abstract form at the 2020 USCAP Annual Meeting in Los Angeles, CA. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Lisa M. Rooper, MD, The Johns Hopkins Medical Institutions, 401 North Broadway, Weinberg 2242, Baltimore, MD 21231 (e-mail: [email protected]). The American Journal of Surgical Pathology: August 2022 - Volume 46 - Issue 8 - p 1025-1035 doi: 10.1097/PAS.0000000000001908 Buy Metrics Abstract 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 y). 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 mo 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. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.