A Case of Medullary Thyroid Carcinoma with de novo V804M RET Germline Mutation
A 33-yr-old man (index patient) was incidentally diagnosed with a 0.7 cm sized nodule in the right thyroid at a general check-up on 30 January 2012 (). He had no personal or family history of hypertension or thyroid cancer. Physical exam was normal. Ultrasound (US) guided fine needle aspiration (FNA) was performed and was suspicious for MTC. Laboratory testing revealed serum calcitonin 23.9 pg/mL (normal range < 10 pg/mL), CEA 5.77 ng/mL (normal range < 5 ng/mL) Ca 9.4 mg/dL, P 3.9 mg/dL, and intact parathyroid hormone (iPTH) 27 pg/mL (normal range 15.0-65.0 ng/mL). The patient underwent total thyroidectomy with central compartment neck dissection for the thyroid tumor. Histological examination revealed MTC without metastasis. Genomic DNA was extracted from the peripheral blood leukocytes of both index patient and at-risk family members. Full sequencing of the RET gene and analyses of exons 10, 11, 13, 14, 15, and 16 were subsequently performed. Genetic analysis of the index case revealed a missense GTG → ATG mutation at codon 804 in exon 14 of the RET proto-oncogene by single-strand conformation polymorphism analysis and direct sequencing using an automated DNA sequencer (3130 Genetic Analyzer, Applied Biosystems, Foster City, CA, USA). This transversion leads to the substitution of valine with methionine (). At-risk family members were tested for exon 14. No other family members carried the V804M RET mutation (). Biochemical tests and thyroid US examinations were performed on family members. On thyroid US, the index patient's mother had multiple small nodules on her left thyroid gland (), but US-guided FNA cytology revealed benign. Laboratory findings including serum Ca, P, iPTH, and calcitonin were within normal limits in all family members.\nPrior to obtaining samples, all individuals included in the study were fully informed about the genetic study and consent was obtained.