Preoperative Detection of Dual TERT Promoter Mutations in Thyroid Cancer: A Case Series

Telomerase reverse transcriptase promoter (TERTp) mutations are associated with aggressive thyroid cancer and are most frequently found in anaplastic and poorly differentiated thyroid cancer. Pre-operative thyroid nodule molecular testing can detect TERTp, denoting a high risk of malignancy and possible aggressive clinical features such as extrathyroidal extension, regional lymph node metastases, and distant metastases. There are two described hot spot point mutations: the more common C228T and a C250T variant. Canonically, these mutations are mutually exclusive and drive monoallelic TERT expression. In this case series, we describe thyroid cancers where both the C228T and C250T variants were detected in preoperative thyroid nodule fine needle aspiration samples sent for Afirma molecular testing. All had co-mutations along with BRAFp.V600E or PIK3CAp.H1047R. Each sample was sent for kinship (relatedness between individuals) analysis to confirm the DNA and RNA samples were from the same patient and not due to sample cross contamination. All cases had confirmed thyroid carcinoma on histopathology after surgical resection. To our knowledge, this is the first report of dual TERTp mutations detected in the preoperative setting in thyroid carcinoma. Clinical correlation with future cases will be of interest, particularly if cases with monoallelic dual TERTp mutations are discovered.