Answer: Medullary carcinoma

Histology: The tumor in the thyroid is neither encapsulated nor circumscribed. Instead, it infiltrates the thyroid parenchyma as variably sized nests set in a highly collagenized background. Within the nests one can discern a microfollicular/acinar arrangement of the tumor cells. At high power, the nuclei have an finely speckled chromatin pattern with inconspicuous nucleoli. There is no evidence of chromatic pallor, intranuclear inclusions or nuclear grooves. Immunohistochemical studies were performed. The tumor cells were found to be immunoreactive for TTF-1, chromogranin and calcitonin; and they were not immunoreactive for thyroglobulin.

Discussion: Medullary thyroid carcinoma (MTC) is a neuroendocrine carcinoma derived from the calcitonin-secreting C-cells of the thyroid. It may exhibit a spectrum of growth patterns and cellular features that can cause confusion with thyroid carcinomas of follicular epithelial origin. MTC can exhibit pseudopapillary formations and even true papillary formations causing confusion with papillary carcinoma. MTCs often demonstrate a prominent insular pattern of growth, a pattern that may lead to an erroneous diagnosis of insular carcinoma. At times the cytoplasm of MTC takes on a very oncocytic appearance, thus causing confusion with Hurthle cell neoplasms. At the extreme, MTCs can demonstrate a very high grade neuroendocrine appearance reminiscent of small cell carcinoma, and these may be mistaken for anaplastic carcinoma. In the present case, the MTC exhibits a prominent follicular pattern of growth that introduces follicular neoplasms into the differential diagnosis.

In all of these instances, immunohistochemistry plays a crucial role in establishing the diagnosis. Unlike most tumors of follicular epithelial origin, MTC is consistently immunoreactive for neuroendocrine markers and non-immunoreactive for thyroglobulin. A word of caution regarding the use of TTF-1 staining in this particular context is in order. TTF-1 expression is not limited to tumors of follicular epithelial origin. Somewhat inconveniently, a significant percentage of MTCs are also positive for TTF-1. Thus, TTF-1 staining has no role in this specific scenario.