Preoperative Role of RAS or BRAF K601E in the Guidance of Surgery for Indeterminate Thyroid Nodules

World J Surg. 2020 Jul;44(7):2264-2271. doi: 10.1007/s00268-020-05487-1.


Background: RAS and K601E BRAF mutations are not a reliable indicator of malignancy in fine-needle aspirations (FNA) of thyroid indeterminate cytologic nodules. We aimed to evaluate the histologic characteristics, the risk of malignancy associated with such mutations in FNA and their potential interest for preoperative clinical management of nodules.

Methods: We evaluated 69 indeterminate thyroid nodules with RAS or K601E BRAF mutations with available histopathologic follow-up. All FNA specimens were indeterminate according to the thyroid Bethesda system. Diagnosis of malignant, benign or indolent neoplasms was classified according to 2017 WHO classification. Carcinoma, NIFTP (noninvasive follicular thyroid neoplasm with papillary-like features) and WDTUMP (well-differentiated tumor of uncertain malignant potential) were considered "surgical," as they require surgical excision. Adenoma was considered "non-surgical." The risk of malignancy and the risk of "surgical disease" were evaluated.

Results: Pathologic evaluation of the 69 mutated nodules demonstrated benign, indolent and malignant histology in 17 cases (25%), 21 cases (30%) and 31 cases (45%), respectively. The risk of malignancy was 45%, and the risk of surgical disease was 75%. The majority of carcinomas were a follicular variant of papillary thyroid carcinoma. On follow-up, there have been no recurrences to date.

Conclusion: Preoperative RAS or BRAF K601E mutations detection in cytologic indeterminate thyroid nodules carries a high risk of surgical disease and may benefit from surgical management. Most surgical lesions harboring those mutations are low-risk tumors, which may be in favor of an initial lobectomy.

MeSH terms

  • Adenocarcinoma, Follicular / diagnosis
  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / pathology
  • Adenocarcinoma, Follicular / surgery
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Biopsy, Fine-Needle
  • Clinical Decision-Making / methods*
  • Female
  • Follow-Up Studies
  • GTP Phosphohydrolases / genetics*
  • Genetic Testing
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Preoperative Care / methods
  • Preoperative Period
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Risk Assessment
  • Thyroid Cancer, Papillary / diagnosis
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Cancer, Papillary / surgery
  • Thyroid Nodule / diagnosis
  • Thyroid Nodule / genetics*
  • Thyroid Nodule / pathology
  • Thyroid Nodule / surgery
  • Thyroidectomy*


  • Biomarkers, Tumor
  • Membrane Proteins
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • GTP Phosphohydrolases
  • NRAS protein, human
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)