Follicular neoplasms of the thyroid gland are most often characterized by follicular-patterned thyrocytes with a neutrally stained cytoplasm, while a minority of cases present with oncocytic differentiation (Hürthle cell tumors). Exceedingly rare variants with a clear cell phenotype have also been reported, both as clear cell follicular thyroid adenomas (ccFTAs) and clear cell follicular carcinomas (ccFTCs). We present a patient with a 30-mm lesion in the thyroid isthmus in which the preoperative cytology proposed a follicular tumor. On postoperative histopathological evaluation, the tumor surprisingly displayed uniform clear-cell differentiation. No nuclear features suggestive of papillary thyroid carcinoma were observed, and differential diagnoses such as medullary thyroid carcinoma, metastatic renal cell, and parathyroid carcinoma were ruled out. The histological investigation revealed intracapsular collections of tumor cells displaying a debatable relation to the surrounding capsule and blood vessels, and the final diagnosis was a follicular tumor of uncertain malignant potential (FT-UMP) as defined by the WHO 2017 classification. As subsets of FT-UMPs with TERT promoter mutations do recur as advanced malignant tumors, a sequencing analysis was undertaken but could not identify TERT promoter mutations at position C228 or C250. To our knowledge, no previous literature has described a clear cell phenotype in an FT-UMP. We therefore advocate that endocrine pathologists should be aware of this entity in addition to ccFTAs and ccFTCs.
TERT Immunohistochemistry Is a Poor Predictor of TERT Promoter Mutations and Gene Expression in Follicular Thyroid Carcinoma
