Molecular diagnosis of a BRAF papillary thyroid carcinoma with multiple chromosome abnormalities and rare adrenal and hypothalamic metastases
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Updated: Jul 17, 2026
Employing Digital Droplet PCR to Detect BRAF V600E Mutations in Formalin-fixed Paraffin-embedded Reference Standard Cell Lines
Published on: October 8, 2015
John A Copland1, Laura A Marlow, Sandra F Williams
1Department of Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida 32224, USA.
Objective:
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.
Design:
Clinical and molecular case study.
Main Outcomes:
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.
Conclusions:
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.
