Molecular diagnosis of a BRAF papillary thyroid carcinoma with multiple chromosome abnormalities and rare adrenal and hypothalamic metastases.

Molecular characterization of thyroid tumors is rarely applied to patient management. Our aim was to demonstrate the application of molecular and cell biology to patient care. Clinical and molecular case study. A 57-year-old man with papillary thyroid carcinoma presented with adrenal and several other presumed metastases, pulmonary nodules, and mediastinal lymphadenopathy. Bronchial carcinoma was entertained for the pulmonary lesions because of a tobacco history. Mediastinal lymph node biopsy was nondiagnostic. Cells from the biopsy were grown in tissue culture and characterized by immunocytochemical (ICC), allele-specific polymerase chain reaction (PCR), reverse transcription (RT)-PCR, DNA sequencing, and cytogenetics. A panel of agents were tested the cells for tumoricidal activity. The cells expressed thyroid-specific markers [thyroid-stimulating hormone receptor (TSH-R), thyroglobulin (TG), sodium iodide symporter (NIS)] and markers [thyroid transcription factor-1 (TTF-1), cytokeratin-7, epidermal growth factor receptor (EGF-R)] present in the primary tumor and adrenal metastasis. The BRAF V600E mutation was detected. The karyotype was 44-48,XY, + der(1) t(1;9)(p13;p13),add(9)(p13),-17,-18, + 0-3mar[cp20]. Lovastatin, gefitinib, paclitaxel, depsipeptide, and 17-AAG inhibited the growth of the cultured cells. Combinations of two or three drugs produced additive or synergistic effects depending upon the combination. Unusual metastases may be associated with multiple molecular and cytogenetic abnormalities. Thus, molecular and cell-biological studies can allow otherwise difficult thyroid tumor diagnosis and may be used for targeted, individualized selection of potential treatments.