BRAF(K601E) mutation in a patient with a follicular thyroid carcinoma

BRAF mutations, the most common genetic alteration associated with papillary thyroid carcinoma (PTC), have never been associated with follicular thyroid carcinoma (FTC) except for one possible case, which, however, had some cellular features of the follicular variant of PTC. Here, we present a patient with a BRAF mutation within a FTC.

A 78-year-old man presented with a nodular lesion 8 cm in size in the right thyroid lobe, coexisting with a goiter. Fine-needle aspiration samples were obtained for cytology, immunocytology, and molecular analysis. Immunoblot analysis on thyroid tissues was performed to evaluate the most important tumor activating pathways. Cytology was consistent with "follicular neoplasia" (negative for galectin-3 immunostaining); molecular analysis on the cytology sample detected a K601E mutation in the exon 15 of the BRAF gene. After total thyroidectomy with lymph-node dissection, the diagnosis of FTC was established by histopathological examination. The BRAF(K601E) mutation was confirmed in DNA obtained from different areas of the FTC. In addition, an activating mutation (E545A) in the PKI3CA oncogene was found in the FTC. As expected, immunoblot analysis showed activation of the PI3K/Akt pathway.

This article describes what may be the first case of a classical FTC carrying a BRAF mutation. Unlike the most common BRAF mutation seen in PTC carcinoma (BRAF(V600E)), this patient's mutation was a BRAF(K601E) mutation that previously has been associated with some cases of the follicular variant of PTC. The BRAF(K601E) mutation should be included in the spectrum of genetic alterations in FTC.