Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma.

Autor:	Rooper LM; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: rooper@jhmi.edu., Agaimy A; Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Erlangen, Germany., Bell D; Department of Pathology, City of Hope Comprehensive Cancer Center, Duarte, California., Gagan J; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas., Gallia GL; Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland., Jo VY; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Lewis JS; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee; Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee., London NR; Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland., Nishino M; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts., Stoehr R; Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg, University Hospital, Erlangen, Germany., Thompson LDR; Head and Neck Pathology Consultations, Woodland Hills, California., Din NU; Department of Pathology and Laboratory Medicine, Aga Khan University, Karachi, Pakistan., Wenig BM; Department of Pathology, Moffitt Cancer Center, Tampa, Florida., Westra WH; Department of Pathology, Icahn School of Medicine at Mount Sinai Hospital, New York, New York., Bishop JA; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
Jazyk:	angličtina
Zdroj:	Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2024 May; Vol. 37 (5), pp. 100448. Date of Electronic Publication: 2024 Feb 16.
DOI:	10.1016/j.modpat.2024.100448
Abstrakt:	Sinonasal tumors with neuroepithelial differentiation, defined by neuroectodermal elements reminiscent of olfactory neuroblastoma (ONB) and epithelial features such as keratin expression or gland formation, are a diagnostically challenging group that has never been formally included in sinonasal tumor classifications. Recently, we documented that most of these neuroepithelial neoplasms have distinctive histologic and immunohistochemical findings and proposed the term "olfactory carcinoma" to describe these tumors. However, the molecular characteristics of olfactory carcinoma have not yet been evaluated. In this study, we performed targeted molecular profiling of 23 sinonasal olfactory carcinomas to further clarify their pathogenesis and classification. All tumors included in this study were composed of high-grade neuroectodermal cells that were positive for pankeratin and at least 1 specific neuroendocrine marker. A significant subset of cases also displayed rosettes and neurofibrillary matrix, intermixed glands with variable cilia, peripheral p63/p40 expression, and S100 protein-positive sustentacular cells. Recurrent oncogenic molecular alterations were identified in 20 tumors, including Wnt pathway alterations affecting CTNNB1 (n = 8) and PPP2R1A (n = 2), ARID1A inactivation (n = 5), RUNX1 mutations (n = 3), and IDH2 hotspot mutations (n = 2). Overall, these findings do demonstrate the presence of recurrent molecular alterations in olfactory carcinoma, although this group of tumors does not appear to be defined by any single mutation. Minimal overlap with alterations previously reported in ONB also adds to histologic and immunohistochemical separation between ONB and olfactory carcinoma. Conversely, these molecular findings enhance the overlap between olfactory carcinoma and sinonasal neuroendocrine carcinomas. A small subset of neuroepithelial tumors might better fit into the superseding molecular category of IDH2-mutant sinonasal carcinoma. At this point, sinonasal neuroendocrine and neuroepithelial tumors may best be regarded as a histologic and molecular spectrum that includes core groups of ONB, olfactory carcinoma, neuroendocrine carcinoma, and IDH2-mutant sinonasal carcinoma. (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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