METASTATIC THYROID-CARCINOMA ARISING FROM CONGENITAL GOITER DUE TO MUTATION IN THE THYROPEROXIDASE GENE

A very large cervical tumor that extended to the upper mediastinum was seen in a newborn after an uneventful pregnancy. The computed axial t omography scan confirmed the presence of a solid mass with precise lim its and scattered foci of calcifications situated in the anterolateral region of the neck. The infant underwent thyroidectomy on the seventh day after birth. Pathological examination revealed a follicular carci noma of the thyroid and probable dyshormonogenetic hyperplastic goiter . At 5 months of age, whole body scans indicated the presence of lung and bone metastases, which were treated with therapeutic doses of radi oiodine. Genomic DNA was obtained from the newborn, her parents, her p aternal aunt, and her paternal grandparents. Denaturing gradient gel e lectrophoresis analysis of PCR fragments corresponding to exon 14 of t he thyroid peroxidase (TPO) gene indicated the presence of a mutant TP O allele present in the propositus, her father, and her paternal grand mother. Sequencing of the TPO gene demonstrated a mutation resulting f rom an insertion of a single extra cytosine in a stretch of seven cyto sines at positions 2505-2511. The insertion caused a frame shift and a stop signal in exon 16. This sequence would translate into a structur ally modified and probably inactive TPO protein. We conclude that the aggressive thyroid metastatic carcinoma arose from a dyshormonogenetic goiter caused by a defective TPO protein.