Hyperfunctioning Papillary Thyroid Carcinoma with a Mutation: The First Case Report and a Literature Review.

INTRODUCTION

Hyperfunctioning papillary thyroid carcinoma (PTC) is rare and consequently, little information on its molecular etiology is available. Although V600E ( c.1799T>A, p.V600E) is a prominent oncogene in PTC, its mutation has not yet been reported in hyperfunctioning PTC.

CASE PRESENTATION

Ultrasonography detected a 26-mm nodule in the right lobe of the thyroid gland of a 48-year-old man. Thyroid function tests indicated that he was hyperthyroid with a TSH level of 0.01 mIU/L (reference range: 0.05-5.00) and a free thyroxine level of 23.2 pmol/L (reference range: 11.6-21.9). TSHR autoantibodies were <0.8 IU/L (reference value: <2.0 IU/L). The Tc thyroid scintigram revealed a round, right-sided focus of tracer uptake by the nodule with a decreased uptake in the remainder of the gland. The patient underwent total thyroidectomy because fine-needle aspiration cytology revealed a malignancy. The histopathological diagnosis was conventional PTC. Subsequent mutational analysis of (exon 15), (exons 1-10), (exons 7-10), (exon 16), , , (codons 12, 13, and 61), and promoter (C250T and C228T) identified a heterozygous point mutation in V600E in a tumor tissue sample. In addition, we identified a D727E polymorphism ( c.2181C>G, p.D727E) in both the tumor and the surrounding normal thyroid tissue.

DISCUSSION AND CONCLUSIONS

We report a case of hyperfunctioning PTC with a V600E mutation for the first time. Our literature search yielded 16 cases of hyperfunctioning thyroid carcinoma in which a mutational analysis was conducted. We identified mutations in 13 of these cases. One case revealed a combination of and mutations; the other case revealed a mutation with a rearrangement. These findings suggest that the concomitant activation of oncogenes (in addition to constitutive activation of the TSHR-cyclic AMP cascade) are associated with the malignant phenotype in hyperfunctioning thyroid nodules.