Answer: Basaloid squamous cell carcinoma

Histology: The surface epithelium is intact without evidence of classic dysplasia. The carcinoma extensively infiltrates the submucosal as expanding nests and lobules with central necrosis. The tumor cells palisade at the periphery of the lobules. Within the lobules, the cells form duct-like structures filled with eosinophilic hyalinized stromal material. The tumor cells have a high N:C ratio imparting a distinctly basaloid appearance. In areas, these basaloid cells show a very abrupt transition with nests of keratinizing squamous cells.

Discussion: The WHO defines the basaloid squamous variant of squamous cell carcinoma (BSCC) as an aggressive, high-grade variant of squamous cell carcinoma composed of both basaloid and squamous components. It is set apart as a distinct subtype of head and neck squamous cell carcinoma based on its striking basaloid morphology (e.g. solid lobules of cells with peripheral pallisading, scant cytoplasm and dark nuclei) and its highly aggressive behavior. It is clinically characterized by rapid growth, a propensity for metastatic spread, and a tendency to present at an advanced stage. Although it can arise anywhere in the upper respiratory tract, it has a strong predilection for the hypopharynx, base of tongue, supraglottic larynx, and the palatine tonsil.

Given its prominent basaloid morphology, it is easily confused with other basaloid neoplasms including the solid variant of adenoid cystic carcinoma and small cell undifferentiated carcinoma. Distinction from adenoid cystic carcinoma relies heavily on the demonstration of clear-cut squamous differentiation. This may take the form of dysplasia of the overlying surface epithelium, abrupt squamous eddies within the basaloid nests, or a separate component of conventional squamous cell carcinoma. Due to the focal nature of these findings, distinction from adenoid cystic carcinoma may be particularly problematic on biopsy.

Immunohistochemistry may be of some use if the distinction between small cell carcinoma and BSCC cannot be reliably made on morphologic grounds. Although BSCC may show positive staining for NSE, it lacks immunoreactivity for more specific markers of neuroendocrine differentiation including chromogranin and synaptophysin. Recently it has been shown that a subset of BSCCs, particularly those arising from the oropharynx, is positive for the human papillomavirus (HPV). HPV testing of basaloid carcinomas arising from the oropharynx is important as those related to HPV are much less aggressive than those that are HPV-unrelated.