Metastatic neuroendocrine tumors to the thyroid gland mimicking medullary carcinoma: a pathologic and immunohistochemical study of six cases.

The clinical, pathological, and immunohistochemical features of six cases of metastatic neuroendocrine and carcinoid tumors to the thyroid simulating medullary thyroid carcinoma (MTC) are described. The patients were women between the ages of 24 and 70 years who, without symptoms or significant past medical histories, presented with either a single mass or multiple thyroid nodules. The primary source of the tumor was only discovered on follow-up. Two of the neoplasms were classical carcinoid tumors, one was a carcinoid predominantly composed of large cells, another showed a prominent oval to spindle cell component, and the two remaining cases were atypical carcinoid/high-grade neuroendocrine carcinomas. The immunohistochemical profile was inconsistent with MTC in that all tumors were negative for calcitonin and only two were focally positive for carcinoembryonic antigen (CEA). A variable pattern of staining for other neuroendocrine and epithelial markers was obtained in each case. Despite the morphologic and immunohistochemical similarities with MTC, the diagnosis of a metastatic neuroendocrine tumor to the thyroid should be favored in the presence of a predominantly interstitial pattern of spread; occurrence of multiple tumor foci; folliculotropism; rosette formations with lumen and cuticular borders; and lack of immunoreactivity for calcitonin and CEA. The differential diagnosis between MTC and metastatic neuroendocrine carcinoma to the thyroid is of importance because of the vast differences in treatment and prognosis.