Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma

Rooper LM, Agaimy A, Bell D, Gagan J, Gallia GL, Jo VY, Lewis JS, London NR, Nishino M, Stöhr R, Thompson LD, Din NU, Wenig BM, Westra WH, Bishop JA (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Modern Pathology Nature Publishing Group: Open Access Hybrid Model Option B

Book Volume: 37

Article Number: 100448

Journal Issue: 5

DOI: 10.1016/j.modpat.2024.100448

Abstract

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.

Authors with CRIS profile

Abbas Agaimy Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Robert Stöhr Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie

Involved external institutions

Vanderbilt University US United States (USA) (US) City of Hope Medical Center US United States (USA) (US) University of Texas Southwestern Medical Center (UT Southwestern) US United States (USA) (US) Johns Hopkins Hospital US United States (USA) (US) Brigham and Women's Hospital (BWH) US United States (USA) (US) Veterans Affairs Healthcare System Boston and Harvard Medical School US United States (USA) (US) Woodland Hills Medical Center US United States (USA) (US) Aga Khan University (AKU) / آغا خان یونیورسٹی‎ PK Pakistan (PK) H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) Icahn School of Medicine at Mount Sinai US United States (USA) (US)

How to cite

APA:

Rooper, L.M., Agaimy, A., Bell, D., Gagan, J., Gallia, G.L., Jo, V.Y.,... Bishop, J.A. (2024). Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma. Modern Pathology, 37(5). https://doi.org/10.1016/j.modpat.2024.100448

MLA:

Rooper, Lisa M., et al. "Recurrent Wnt Pathway and ARID1A Alterations in Sinonasal Olfactory Carcinoma." Modern Pathology 37.5 (2024).

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