Answer: Follicular adenoma, signet ring cell type

Histology: The nodule is thinly encapsulated without evidence of invasive tumor growth beyond the capsule. The lesion demonstrates a microfollicular pattern of growth. The cells lining the follicles exhibit cytoplasmic clearing. In some cells, large cytoplasmic vacuoles compress and indent the nucleus in a fashion that resembles lipoblasts.

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. 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. Further, immunoreactivity for thyroglobulin as well as TTF-1 eliminates the possibility of a liposarcoma or a metastasis from the breast or stomach.

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.