Answer: Squamous cell carcinoma arising in anaplastic thyroid carcinoma

Histology: The tumor is biphasic having two distinct components. One component demonstrates a papillary growth pattern. The cells lining the papillae are columnar and have atypical nuclei showing enlargement, angulations, grooves and crowding. The other components demonstrates solid nested growth pattern. The tumor cells have pink glassy cytoplasm that in some areas shows frank keratinization. This component is highly infiltrative with prominent perineural invasion. The tumor cells are pleomorphic, the mitotic rate is very high, and necrosis is prominent.

Discussion: Several morphologic variants of anaplastic thyroid carcinoma are recognized including a spindle cell variant, a giant cell variant and a squamoid variant. As for the squamoid variant, it is somewhat unusual to encounter overt epidermoid differentiation including the presence of keratin pearls. In these instances, some prefer the designation of squamous cell carcinoma arising in an undifferentiated carcinoma. These are aggressive, rapidly fatal neoplasms that do not respond to radioactive iodine therapy.

Primary squamous cell carcinomas of the thyroid are uncommon and must be distinguished from secondary involvement of the thyroid by a mucosal primary. Keeping in mind that undifferentiated thyroid carcinomas are generally not immunoreactive for TTF-1 or thyroglobulin, a diligent search for a focal component of well-differentiated thyroid carcinoma is the best way to confirm thyroid origin. One must be careful not to dismiss the squamous component as simple metaplasia. About one-third of well-differentiated papillary carcinomas harbor focal or diffuse areas of squamous metaplasia, but these areas do not demonstrate the necrosis, pleomorphism and high mitotic activity that marks anaplastic carcinoma.