Answer: Follicular adenoma, signet ring variant

Histology: The nodule measures 4 cm in diameter, and it is thinly encapsulated throughout without evidence of invasive tumor growth beyond the capsule. The lesion demonstrates a nested pattern of growth. The cells demonstrate prominent cytoplasmic clearing. In some of these cells a large vacuole distends the cytoplasm and compresses the nucleus.

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.

Although the cytoplasmic vacuolization and nested arrangement of the tumor cells raises the possibility of metastatic renal cell carcinoma, the tumor lacks the prominent delicate vascularity of renal cell carcinoma. Immunohistochemical stains should unable a definite diagnosis in difficult cases. Follicular adenomas in all of its variants are consistently immunoreactive for thyroglobulin and TTF-1; and they are not immunoreactive for RCC.