Reply to Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical treatment of patients with indeterminate thyroid nodules: A prospective case series of 960 patients


We greatly appreciate the thoughtful comments provided by our colleagues from University Medical Center Utrecht regarding our article.[1] The authors made a valid point that the implications of our study are largely dependent on institutional practice patterns. As noted, it is the practice at our institution to recommend a total thyroidectomy as the initial surgical procedure for patients with Bethesda category V nodules and Bethesda category III nodules with particularly worrisome atypical features. However, this is not the case at all centers worldwide, and there is even discrepancy among centers within the United States. Therefore, any surgeon who always recommends a hemithyroidectomy for any nodule that is not determined to be clearly malignant on preoperative fine-needle aspiration may come to an opposite conclusion to the one that we have proposed.

We generally agree with Lodewijik et al that if preoperative BRAF(V600E) screening is to be offered, it is likely to be most beneficial to patients with Bethesda category V nodules as opposed to those with Bethesda III and IV nodules. As reported in our study,[1] the sensitivity of BRAF screening for detecting malignancy among patients with Bethesda III and IV nodules was only 3% compared with 42% among patients with Bethesda V nodules. To follow on the argument proposed by Lodewijik et al, 272 Bethesda III or IV nodules had to be tested to detect 2 BRAF(V600E) mutations. Although we have not formally performed the calculations, we doubt that most centers would find this to be a cost-effective strategy given such a low pretest probability of identifying a mutation.

Ultimately, we believe that the most effective use of preoperative BRAF(V600E) screening is for patients who have worrisome thyroid nodules and are resistant to commit to a total thyroidectomy because of the 20% to 30% chance that the nodule is benign, meaning that they have unnecessarily committed to lifelong thyroid hormone replacement therapy. Selectively offering those patients preoperative BRAF(V600E) screening may result in preoperative confirmation of malignancy and thereby avoid a 2-stage procedure.

Although the management of Bethesda category V nodules may differ between centers, the management of Bethesda III and IV nodules is less variable. Therefore, the main conclusion of our study[1] that preoperative BRAF(V600E) should not routinely be performed on all patients with Bethesda category III and IV nodules due to the very low likelihood of identifying a mutation among this subgroup is likely to apply to most centers within the United States and abroad.


No specific funding was disclosed.


The authors made no disclosures.

  • David A. Kleiman, MD

  • Rasa Zarnegar, MD

  • Thomas J. Fahey III, MD

  • Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York