Case Series of Two TERT Mutation-Positive Benign Follicular Thyroid Adenomas

Telomerase reverse transcriptase (TERT) promoter mutations have been found to increase telomerase activity and thereby drive oncogenic processes. TERT mutations have been identified in many types of malignancies and are frequently found in anaplastic, follicular, and papillary thyroid cancer. Genetic testing has become an important tool in evaluating thyroid lesions especially with indeterminant fine needle biopsy results. Studies have shown TERT promoter mutations to be associated with poor prognosis and are only very rarely found in benign thyroid lesions.

Case Description :

Case 1: A 4.1 cm thyroid nodule was discovered in a 49-year-old man on imaging done for dysphonia. Fine needle aspiration cytology resulted with follicular cell neoplasm. Genetic testing with ThyroSeq® Genomic Classifier was positive for TERT promoter mutation and multiple chromosomal copy number alterations. This finding was estimated to have an 80% chance of malignancy. Patient subsequently underwent total thyroidectomy. Pathology was reported as follicular adenoma with cytoplasmic oxyphilic measuring 5.0 cm in size.
Case 2: A 65-year-old woman presented with neck pain; MRI revealed a 3 cm thyroid nodule. Fine needle aspiration cytology reported atypia of undetermined significance. The sample was sent for genetic testing and ThyGenNEXT® oncogene panel returned with NRAS and TERT mutations. This was reported as 95% risk of malignancy. Total thyroidectomy was recommended however patient chose hemithyroidectomy. Pathology was reported as follicular adenoma 2.8cm in size with qualification that lesion did not demonstrate vascular or convincing capsular invasion but did have thickened capsule.

Discussion :

The TERT promoter mutation is very rarely identified in follicular adenomas. In a review of six studies, 0 cases out of 189 of follicular adenomas reviewed were positive for TERT promoter mutation. In one study, the TERT promoter mutation was found in a thyroid lesion initially determined as follicular adenoma but later proved to be follicular carcinoma with recurrence and metastasis. Therefore, when TERT mutation is found in an apparent follicular adenoma, initial misdiagnosis should be considered. In the cases presented, pathology was confirmed at review boards. Another possibility is genetic findings that precede histological or pathological findings of malignancy, although TERT mutations usually occur late in carcinogenesis. Either possibility suggests that while TERT promoter mutations can be found in benign follicular adenomas, because this is rare, closer monitoring is probably warranted.