Answer: Basaloid squamous cell carcinoma

Histology: The tumor is biphasic. One component is characterized by conventional squamous cell carcinoma. Here the tumor infiltrates a desmoplastic stroma as irregular cords and nests of cells with overt cytoplasmic keratinization. The second component of the tumor is present as tumor cells that invade and fill the subepithelial tissues as expanding nests and lobules. The presence of cellular necrosis within the center of the tumor lobules is a prominent finding. In some lobules the tumor cells often palisade at the periphery. The tumor cells take on a basaloid appearance in that they have a very immature appearance, they exhibit a high nuclear to cytoplasmic ratio, and they lack abundant eosinophilic cytoplasm indicating more mature squamous differentiation. Within the basaloid nests there are occasional abrupt zones of keratinization with keratin pearls formations.

Discussion: Basaloid squamous cell carcinoma is a variant of SCC that is set apart by its prominent basaloid morphology and by its aggressive clinical behavior. The term basaloid refers to the immature appearance of the tumor cells. They exhibit a high nuclear to cytoplasmic ratio, lacking the abundant eosinophilic cytoplasm indicating more mature squamous differentiation. Some areas of the tumor must show unambiguous squamous differentiation, although these areas may be focal and are dominated by the basaloid component. This squamous element may take the form of surface dysplasia, an associated conventional invasive SCC, or abrupt zones of keratinization within the basaloid nests.

Basaloid SCC may exhibit morphological overlap with other tumors characterized by a prominent basaloid morphology including the solid variant of adenoid cystic carcinoma, small cell carcinoma, and HPV-associated SCC. Unlike basaloid SCC, the solid variant of adenoid cystic carcinoma is not associated with a squamous component. It can be safely eliminated from the differential diagnosis when surface dysplasia, zones of keratinization, and/or an invasive SCC are identified. Conversely, the absence of a squamous component and the presence of a classic cribriform growth pattern support the diagnosis of adenoid cystic carcinoma. The distinction of basaloid SCC from small cell carcinoma generally requires the integration of histological and immunohistochemical findings. Immunohistochemical evidence of neuroendocrine differentiation (e.g. positivity for chromogranin, synaptophysin, CD56) in a high grade carcinoma characterized by nuclear hyperchromasia, nuclear molding, and extreme mitotic activity supports the diagnosis of small cell carcinoma over basaloid SCC. TTF-1 is variable expressed in small cell carcinomas, but it is not expressed in basaloid SCCs. The expression of high molecular weight cytokeratins (e.g. CK 5/6) is nearly constant in basaloid SCCs, but they are not expressed in small cell carcinomas.

Squamous cell carcinomas caused by HPV consistently demonstrate basaloid features, even to the point where they cannot be distinguished from basaloid SCC on histological grounds. Morphologic similarities aside, these HPV-related SCCs do not share the same aggressive clinical behavior that characterizes the basaloid SCC. Determination of HPV tumor status is currently the only reliable means of differentiating a highly aggressive basaloid SCC from a prognostically favorable HPV-related SCC. In this particular case, origin from the oral tongue (as opposed to posterior tongue) would strongly favor a non-HPV related cancer.