Answer: Follicular adenoma with mucinous metaplasia (signet ring follicular adenoma)

Histology: The nodule measures 3 cm in diameter, and it is thinly encapsulated without evidence of invasive tumor growth beyond the capsule. The lesion demonstrates a microfollicular pattern of growth. The follicles are filled with a wispy bluish substance, and the cells lining the follicles demonstrate cytoplasmic clearing. In some of these cells a large vacuole distends the cytoplasm and compresses the nucleus. These cytoplasmic vacuoles, as well as the material filling the follicles, are mucicarmine positive and alcian blue positive. By immunohistochemistry, this material is also thyroglobulin positive.

Discussion: Signet-ring follicular adenoma is a rare variant of follicular adenoma characterized by the presence of large cytoplasmic vacuoles that distend and displace the nucleus, thereby imparting a signet ring configuration. When these vacuoles have a basophilic quality, mucin stains are often positive. The consistent finding of strong immunoreactivity for thyroglobulin has lent support to the belief that the cytoplasmic vacuoles represent protein-polysaccharide complexes derived from partial degradation of thyroglobulin.

Whatever its chemical composition, a signet-ring cell morphology should not be taken as unequivocal evidence of malignancy when dealing with thyroid nodules. This finding by itself is of no prognostic relevance as cytoplasmic vacuolization can be encountered in both follicular adenomas and follicular carcinomas. For signet-ring follicular neoplasms, the distinction between benign and malignant still rests on the presence or absence of invasive tumor growth.