SQUAMOUS DIFFERENTIATION IN SMALL-CELL CARCINOMA OF THE PAROTID-GLAND

Small-cell anaplastic carcinomas comprise 1% to 2% of major salivary g land malignant tumors and demonstrate an aggressive clinical course. T he initial classification of salivary small-cell anaplastic carcinoma was based on the ultrastructural identification of membrane-bound dens e core granules, confirming neuroendocrine differentiation. These neur oendocrine-type small-cell carcinomas were felt to arise from neuroend ocrine stem cells that migrated to the salivary gland from the neural crest. Absent neuroendocrine differentiation by ultrastructural evalua tion was felt to signify origin from ductal cells. Immunohistochemical study has revised this concept because many small-cell carcinomas exp ress at least one neuroendocrine marker, even in the absence of ultras tructural evidence of neuroendocrine differentiation. In addition, gla ndular differentiation both by ultrastructural and light microscopic s tudy has been found in cases showing neuroendocrine differentiation. U ltrastructural evidence for squamous differentiation, such as desmosom es and tonofilaments, has also been recognized. These new findings hav e led to a revision of the old histogenetic hypothesis. All of these s mall-cell carcinomas are presumed to arise from a hypothetical ductal stem cell that can undergo neuroendocrine, squamous, or glandular diff erentiation. We report a small-cell anaplastic carcinoma of the left p arotid gland in a 61-year-old man with squamous differentiation identi fied by light microscopy and confirmed by immunohistochemical expressi on 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 t o well-differentiated squamous differentiation, which was identified r eadily by light microscopy. Our findings support this new hypothesis o f a single multipotential stem cell by demonstrating bidirectional neu roendocrine and squamous differentiation.