Combined Neuroendocrine and Squamous Cell Carcinoma of the Sinonasal Tract: A Morphologic and Immunohistochemical Analysis and Review of Literature

Authors

Shweta Agarwal, Department of Pathology, University of New Mexico School of Medicine, University of New Mexico, MSC08 4640, Albuquerque, NM, 87131, USA; Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA
Annemieke van Zante, Department of Pathology, University of California San Francisco, San Francisco, CA, USA
Michaela L. Granados, Department of Pathology, University of New Mexico School of Medicine, University of New Mexico, MSC08 4640, Albuquerque, NM, 87131, USA

Document Type

Article

Publication Date

12-1-2022

Abstract

Sinonasal malignancies constitute 3% of head and neck cancers, with squamous cell carcinoma (SCC) the most common histology. Neuroendocrine carcinomas (NEC) are rare, with a subset showing neuroendocrine carcinoma and a non-neuroendocrine component. The pathogenesis of these combined tumors is largely unknown, and TP53 driver mutations may play a role. A database search for combined NEC was performed across two institutions (UNM and UCSF) spanning 15 years. Excluding NUT midline carcinoma, 3 cases met inclusion criteria. All were morphologically NEC + SCC and underwent a comprehensive immunohistochemical evaluation. Tumors demonstrated two components histologically: moderately to poorly differentiated SCC and high-grade NEC. Divergent differentiation was confirmed with lineage-specific markers. Only one patient received neoadjuvant chemotherapy prior to surgery, with a remarkable response (a marked decrease in the size of the primary lesion and resolution of liver metastases). Immunohistochemical staining for p53 was increased in 2 of 3 cases (both components), suggesting a role in the carcinogenesis of these tumors. Aberrant expression of beta-catenin was not identified. One case tested positive for p16, which can be seen in high grade NECs due to inactivation of Rb gene. Additionally, both cases with a small cell NEC component expressed PD-L1, suggesting that immunotherapy may be an effective treatment. Findings in this study support the role of p53 mutation in a subset of combined NEC + SCC of the sinonasal tract. Recognition of this rare entity is essential for optimal management of these aggressive neoplasms.

Recommended Citation

Agarwal S, van Zante A, Granados ML. Combined Neuroendocrine and Squamous Cell Carcinoma of the Sinonasal Tract: A Morphologic and Immunohistochemical Analysis and Review of Literature. Head Neck Pathol. 2022 Dec;16(4):1019-1033. doi: 10.1007/s12105-022-01457-2. Epub 2022 May 4. PMID: 35507300; PMCID: PMC9729485.