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 ( = 8) and ( = 2), inactivation ( = 5), mutations ( = 3), and hotspot mutations ( = 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 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 mutant sinonasal carcinoma.

中文翻译：

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鼻窦嗅癌中复发性 Wnt 通路和 ARID1A 改变

具有神经上皮分化的鼻窦肿瘤，由让人想起嗅神经母细胞瘤（ONB）的神经外胚层成分和角蛋白表达或腺体形成等上皮特征定义，是一个诊断上具有挑战性的群体，从未正式纳入鼻窦肿瘤分类。最近，我们记录了大多数神经上皮肿瘤具有独特的组织学和免疫组织化学发现，并提出术语“嗅觉癌”来描述这些肿瘤。然而，嗅癌的分子特征尚未得到评估。在本研究中，我们对 23 种鼻鼻腔嗅癌进行了靶向分子分析，以进一步阐明其发病机制和分类。本研究中包含的所有肿瘤均由高级神经外胚层细胞组成，这些细胞对 Pankeratin 和至少 1 种特定的神经内分泌标记物呈阳性。很大一部分病例还表现出玫瑰花结和神经原纤维基质、具有可变纤毛的混合腺体、外周 p63/p40 表达和 S100 蛋白阳性支持细胞。在 20 个肿瘤中发现了复发性致癌分子改变，包括影响 ( = 8) 和 ( = 2) 的 Wnt 通路改变、失活 ( = 5)、突变 ( = 3) 和热点突变 ( = 2)。总体而言，这些发现确实证明了嗅癌中存在复发性分子改变，尽管这组肿瘤似乎不是由任何单一突变来定义的。与先前报道的 ONB 改变的最小重叠也增加了 ONB 和嗅癌之间的组织学和免疫组织化学分离。相反，这些分子发现增强了嗅觉癌和鼻窦神经内分泌癌之间的重叠。神经上皮肿瘤的一小部分可能更适合突变型鼻窦癌的取代分子类别。此时，鼻窦神经内分泌和神经上皮肿瘤最好被视为一个组织学和分子谱，包括 ONB、嗅癌、神经内分泌癌、和突变型鼻窦癌。