Answer: Metastatic HPV-related squamous cell carcinoma

Histology: Microscopically, the tumor is composed of basaloid cells growing as solid expanding lobules. Within the lobules, the cells exhibit a trabecular growth pattern with pallisading of cells at the periphery of the nests. The cells have scant cytoplasm, hyperchromatic nuclei and a high nuclear to cytoplasmic ration. Within the solid nests are small cystic spaces filled with eosinophilic stromal material. The solid nests also demonstrate foci of abrupt keratinization. Special studies were performed. An in-situ hybridization assay for high risk HPV demonstrates punctate hybridization signals in the tumor cell nuclei.

Discussion: HPV-related squamous cell carcinoma of the head and neck has a consistent histomorphologic appearance that includes a distinct basaloid quality (i.e. lobules of tumor cells with hyperchromatic nuclei and a high nuclear to cytoplasmic ratio). Accordingly, HPV-related squamous cell carcinoma often occurs in the differential of other basaloid carcinomas including the basaloid squamous variant of squamous cell carcinoma and the solid variant of adenoid cystic carcinoma.

Despite striking morphologic overlap with the solid variant of adenoid cystic carcinoma (e.g. basaloid cells, stromal deposition of eosinophilic ground substance, and ductal formations), the squamous nature of this tumor is evidenced by the presence of abrupt zones of keratinization. Indeed, the presence of keratinization, even when focal, is a key finding in separating basaloid squamous cell carcinoma from the solid variant of adenoid cystic carcinoma.

One could argue that this tumor demonstrates classic features of the basaloid squamous variant of head and neck squamous cell carcinoma, and that it should be classified as such based on these morphologic features. However a subset of basaloid squamous cell carcinomas, particularly those arising in the oropharynx, is related to high risk HPV. Identification of this subset by the detection of HPV is important as the HPV-positive tumors are associated with much more favorable clinical outcomes. For basaloid carcinomas arising in the oropharynx or presenting as lymph node metastases, we advocate routine HPV testing to separate out the less aggressive HPV-related tumors from the highly aggressive HPV-negative basaloid squamous variant.