Histopathologic and Clinical Characterization of Thyroid Tumors Carrying theBRAFK601EMutation

Abstract

Background While the BRAF V600E mutation's association with aggressive histopathological tumor features and clinical behavior has been extensively studied in papillary thyroid carcinoma (PTC), the BRAF K601E mutation has not been well characterized. In this paper we report the largest series to date of BRAF K601E mutated thyroid nodules. Methods Histopathologic, cytologic, and molecular reports over a period of seven years (06/2007-06/2014) were reviewed to identify thyroid cases with various types of BRAF mutations. All cases positive for BRAF K601E mutation were reviewed to confirm histopathologic diagnosis and establish tumor variant, clinical charts were reviewed to obtain clinical characteristics and follow-up information. Results The BRAF K601E mutation was identified in 39 patients and comprised 5.3% of all BRAF mutations noted in thyroidectomy specimens. Twenty seven (93%) out of 29 nodules with BRAF K601E mutated tumors with surgical pathology results available for review were papillary thyroid carcinomas (PTC), 1 (3.4%) was a follicular thyroid carcinoma and one (3.4%) was a follicular adenoma. The majority of K601E-mutant PTCs (20 cases) were follicular variant PTC (FVPTC). Encapsulation was present in all but one case, and one case showed capsular invasion. Coexisting mutations overall were not identified in BRAF K601E- mutated thyroid nodules except on a case that exhibited a complex K601E+T599I mutation and had a classic papillary thyroid carcinoma phenotype. The majority of K601E mutant nodules were T1 lesions (69%) and T2 lesions (28%) by TNM staging. With a median follow-up of 19.6 months, no structural or biochemical recurrence or metastases were found in patients with an isolated BRAF K601E mutation. Conclusions: The BRAF K601E mutation is the second most common BRAF mutation after V600E found in thyroid nodules. Unlike BRAF V600E, this mutation is strongly associated with follicular-patterned cancer, particularly with the encapsulated follicular variant of PTC and may also be found in a follicular thyroid carcinoma. Overall, BRAF K601E mutant tumors show better clinical outcomes than BRAF V600E positive tumors, and preoperative BRAF K601E analysis can provide important prognostic information for use in clinical management.