Classification of Sinonasal Tract Neoplasms

The sinonasal tract and pharynx are anatomically small regions that are host to a wide variety of tumor types including epithelial, neuroendocrine/neuroectodermal, melanocytic, hematolymphoid and mesenchymal benign and malignant neoplasms. Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the head and neck and most often is associated with tobacco and alcohol use. However, viruses including human papillomavirus (HPV) and Epstein-Barr virus (EBV) have been implicated as being causative of oropharyngeal and nasopharyngeal carcinomas, respectively. HPV-related SCC and EBV-related SCC share overlapping morphologic features and both may present with metastasis to the cervical neck lymph nodes as occult primary cancers. Further, several morphologic variants of HPV-related carcinomas have been identified, expanding the tumor types associated with HPV. With advances in molecular diagnoses, several unique and distinct tumors types that heretofore may have been classified within the histologic spectrum of sinonasal undifferentiated carcinoma (SNUC) have been identified. Such tumors include NUT (midline) carcinoma and SMARCB1 (INI-1)-deficient carcinomas. The sinonasal tract and pharynx may give rise to the group of small round cell undifferentiated malignant neoplasms that, in small biopsies, pose diagnostic challenges given their overlapping morphologic features. Differentiating these tumor types requires immunohistochemical staining and/or molecular diagnostics in order to guide proper treatment. This chapter provides an overview of the array of neoplasms that may occur in the sinonasal tract and pharynx. In the upper aerodigestive tract (UADT), the more common sites for clinically early stage squamous cell carcinoma (SCC) in the form of intraepithelial dysplasia are the oral cavity and the larynx. The most common histologic type of intraepithelial dysplasia of the UADT is the keratinizing or differentiated type. In contrast to uterine cervical dysplasia, full thickness intraepithelial dysplasia or carcinoma in situ (CIS) is not a prerequisite for progression to invasive carcinoma, which may be seen with dysplastic epithelium wholly limited to basal zone epithelium. As a result of this phenomenon, the classification of UADT intraepithelial dysplasia may be subjective without diagnostic consensus among pathologists. Recent changes in the classification of UADT keratinizing (differentiated) intraepithelial dysplasia to a 2 tiered system including low-grade intraepithelial dysplasia (mild dysplasia) and high-grade intraepithelial dysplasia (including moderate and severe dysplasia/CIS) has to a large extent reduced the subjectivity and lack of consensus in their diagnosis. A focus of this chapter is to detail the morphologic spectrum of the keratinizing (differentiated) intraepithelial dysplastic lesions. Similarly, given the common occurrence of laryngeal SCC and variants thereof, this chapter details their clinical and pathologic findings. Neuroendocrine carcinomas (NEC) uncommonly occur in the head and neck but have a predilection to occur in the (supraglottic) larynx. The pathologic spectrum of the group of NEC is addressed in this chapter including the recent identification of the large cell type of poorly-differentiated NEC, now recognized and included in the classification of NEC of the head and neck.