Abstract
Background: Hyperfunctioning papillary thyroid carcinoma (PTC) is a rare tumor and accounts for less than 0.1% of all thyroid tumors. Information about its driver mutations is limited. Our literature search yielded 16 cases wherein a mutational analysis was conducted. Thyrotropin receptor (TSHR) mutations were identified in 11 of these cases. One case revealed a combination of TSHR and KRAS mutations. No mutations were identified in the other four cases. BRAFV600E is a prominent oncogene in PTC; however, hyperfunctioning PTC with this mutation has not yet been reported.
Clinical Case: In a 48-year-old man, ultrasonography (US) during an annual medical checkup revealed a nodule at the right lobe of the thyroid gland. He visited the outpatient clinic for further evaluation. Thyroid function tests indicated that he was hyperthyroid with TSH level of 0.01 mIU/L (reference range: 0.05-5.00), free thyroxine level of 1.8 ng/dL (reference range: 0.9-1.7), and free triiodothyronine level of 4.3 pg/mL (reference range: 2.3-4.0). Serum thyroglobulin was 62.1 ng/mL (reference range: <33.7) and TSHR autoantibodies (TRAb) was <0.8 IU/L (reference range: <2.0 IU/L). B-mode US revealed a hypoechoic, heterogeneous nodule with largest diameter of 25 mm, and it had a jagged border and microcalcification. Color Doppler US revealed increased intranodular vascularity. The 99mTc thyroid scintigram revealed a round, right-sided focus of tracer uptake by the nodule with suppression in the remainder of the gland. These findings were consistent with an autonomously-functioning thyroid nodule. The patient underwent total thyroidectomy because fine-needle aspiration cytology revealed a malignant cytological diagnosis. The histopathological diagnosis of the patient was PTC, tall cell variant, pT2, pEx0, pN1b, and M0. Subsequent mutational analysis of BRAF (exon 15), TSHR (exons 9 and 10), GNAS (exons 7-10), KRAS, NRAS, HRAS (codons 12, 13, and 61), and TERT promoter (C250T and C228T) only identified a heterozygous point mutation in BRAFV600E in tissue samples.
Conclusion: We report for the first time a case of hyperfunctioning papillary thyroid carcinoma with a BRAF mutation.
Gray-Scale and Color Doppler US Features Corresponding to Histological Subtypes of Papillary Thyroid Carcinoma