Sinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus

Abstract

The sinonasal tract is one of the least frequent sites for squamous cell carcinoma in the head and neck. However, it is still a complex tumor type for pathologists because there are numerous histologic variants with unusual morphologic features, several non-squamous carcinomas in the differential diagnosis that can have similar morphology and even squamous differentiation, and because of the increasing recognition of human papillomavirus (HPV) in a subset of the tumors. In addition, the unique and complex anatomy of the sinonasal tract can make proper staging and management of patients' tumors quite challenging. This article reviews sinonasal tract squamous cell carcinoma in depth and provides the latest data on Schneiderian papillomas and HPV in their pathogenesis.

Keywords: Human papillomavirus; Nonkeratinizing; Sinonasal; Squamous cell carcinoma.

Fig. 1

Keratinizing and nonkeratinizing squamous cell carcinoma of the sinonasal tract. Keratinizing (or conventional) squamous cell carcinoma on low power (a-×4 magnification) showing large, irregular, and stellate nests of tumor cells in a lightly basophilic (desmoplastic) stroma and on high power (b-×20 magnification) showing cells with abundant, eosinophilic cytoplasmic and foci of keratinization. Nonkeratinizing squamous cell carcinoma on low power (c-×4 magnification) with large, rounded nests of blue cells with little stromal reaction, and on higher power (d-×40 magnification), oval, hyperchromatic nuclei with minimal cytoplasm and minimal areas of maturing squamous differentiation

Fig. 2

Histologic variants of squamous cell carcinoma. Basaloid squamous cell carcinoma consists of nested tumor with rounded profiles that “mold” to one another in a jigsaw puzzle type pattern (a-×4 magnification) with necrosis and areas of hyalinized, collagenous stroma. On higher power, the nuclei are round with abundant surrounded hyaline material forming thin lines between some nests (arrow) (b-×20 magnification). Papillary squamous cell carcinoma consists predominantly of full-thickness dysplastic squamous cells lining papillary structures (c-×1.25 magnification), with cells above the basement membrane. On higher power (d-×10 magnification), the papillae can be seen with lining cells with eosinophilic cytoplasm, angulated, hyperchromatic nuclei and no maturation. Adenosquamous carcinoma (e-×4 magnification) consists of squamous cell carcinoma, here the angulated nests in a fibrous stroma, but with “punched out” gland spaces with smooth linings. On higher power (f-×20 magnification), flocculent mucin material can be seen in the large gland space but there are also several tumor cells with basophilic, intracytoplasmic mucin globules. Verrucous carcinoma is a “hyper-differentiated” tumor consisting of very thick squamous lining with hyperkeratosis and “glassy”, brightly eosinophilic cytoplasm (g-×4 magnification). On higher power (h-×20 magnification), the tumor cells have abundant cytoplasm and pushing borders without irregular infiltration or stromal reaction

Fig. 3

Spindle cell (sarcomatoid) carcinoma. A gross photograph of a total rhinectomy specimen for spindle cell carcinoma a shows violaceous nodules of tumor (asterisks) bulging underneath the skin of the nasal bridge. Histologically, the tumor was biphasic, consisting predominantly of keratinizing type squamous cell carcinoma but with sheet-like areas of spindle cells (b-×4 magnification) in a vaguely fascicular pattern with hyperchromatic, pleomorphic nuclei, collagenous to myxoid stroma (c-×20 magnification) and abundant mitoses, including atypical ones

Fig. 4

Human papillomavirus (HPV) in situ hybridization and p16 immunohistochemistry. HPV RNA can be detected by emerging in situ hybridization for E6/E7 mRNA in tissue slides, here (a-×20 magnification) with granular, brown staining in all of the tumor cells. In situ hybridization for high risk HPV DNA is common (b-×20 magnification), here showing multifocal, punctate, blue signals in the nuclei of tumor cells. p16 immunohistochemistry is a well established surrogate marker of transcriptionally-active high risk HPV in tumors with a stain pictured here where there is strong, nuclear and cytoplasmic staining (c-×4 magnification) in almost all tumor cells