Locally invasive classical papillary thyroid carcinoma with TSH receptor I568T mutation: case report

Autonomous thyroid adenomas are caused by activating mutations in the genes encoding the thyroid-stimulating hormone receptor (TSHR) or mutations in the Gas subunit of the TSHR. Nodules with suspicious sonographic features should be submitted to fine-needle aspiration. Additional molecular testing may be performed to characterize the thyroid nodule's malignant potential further. We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a TSHR I568T mutation after an ultrasound showed suspicious sonographic features and fine-needle aspiration was 'suspicious for malignancy'. The patient underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma. Most reports of TSHR I568T mutation have been seen in patients with benign thyroid conditions. While there is insufficient data to suggest that the TSHR I568T mutation causes aggressive thyroid malignancy, we believe clinicians who identify the presence of this mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology. Learning points Germline and somatic activating mutations in the genes coding for the thyroid-stimulating hormone receptor (TSHR) have been frequently reported in familial and sporadic autonomous thyroid adenomas and non-autoimmune hyperthyroidism. Most reports of I568T mutation have been detected in patients with benign thyroid conditions. We present a patient who underwent whole-transcriptome RNA-sequencing that indicated a I568T mutation and subsequently underwent thyroid resection and was found to have a locally invasive classical papillary thyroid carcinoma. Clinicians who identify the presence of I568T mutation on genome sequencing should be cautious about the possibility of locally invasive thyroid malignancy, especially when associated with Bethesda V cytopathology.