Squamous differentiation in small-cell carcinoma of the parotid gland

Small-cell anaplastic carcinomas comprise 1% to 2% of major salivary gland malignant tumors and demonstrate an aggressive clinical course. The initial classification of salivary small-cell anaplastic carcinoma was based on the ultrastructural identification of membrane-bound dense core granules, confirming neuroendocrine differentiation. These neuroendocrine-type small-cell carcinomas were felt to arise from neuroendocrine stem cells that migrated to the salivary gland from the neural crest. Absent neuroendocrine differentiation by ultrastructural evaluation was felt to signify origin from ductal cells. Immunohistochemical study has revised this concept because many small-cell carcinomas express at least one neuroendocrine marker, even in the absence of ultrastructural evidence of neuroendocrine differentiation. In addition, glandular differentiation both by ultrastructural and light microscopic study has been found in cases showing neuroendocrine differentiation. Ultrastructural evidence for squamous differentiation, such as desmosomes and tonofilaments, has also been recognized. These new findings have led to a revision of the old histogenetic hypothesis. All of these small-cell carcinomas are presumed to arise from a hypothetical ductal stem cell that can undergo neuroendocrine, squamous, or glandular differentiation. We report a small-cell anaplastic carcinoma of the left parotid gland in a 61-year-old man with squamous differentiation identified by light microscopy and confirmed by immunohistochemical expression of predominantly high rather than low molecular weight cytokeratins. This tumor is distinctive because it shows an abrupt transition from small-cell anaplastic carcinoma with neuroendocrine differentiation to well-differentiated squamous differentiation, which was identified readily by light microscopy. Our findings support this new hypothesis of a single multipotential stem cell by demonstrating bidirectional neuroendocrine and squamous differentiation.