title: What to do with thyroid nodules showing benign cytology and BRAF(V600E) mutation? A study based on clinical and radiologic features using a highly sensitive analytic method.
abstract: BACKGROUND
  BRAF(V600E) mutation analysis has been used as a complementary diagnostic tool to ultrasonography-guided, fine-needle aspiration (US-FNA) in the diagnosis of thyroid nodule with high specificity reported up to 100%. When highly sensitive analytic methods are used, however, false-positive results of BRAF(V600E) mutation analysis have been reported. In this study, we investigated the clinical, US features, and outcome of patients with thyroid nodules with benign cytology but positive BRAF(V600E) mutation using highly sensitive analytic methods from US-FNA.
  
  
  METHODS
  This study included 22 nodules in 22 patients (3 men, 19 women; mean age, 53 years) with benign cytology but positive BRAF(V600E) mutation from US-FNA. US features were categorized according to the internal components, echogenicity, margin, calcifications, and shape. Suspicious US features included markedly hypoechogenicity, noncircumscribed margins, micro or mixed calcifications, and nonparallel shape. Nodules were considered to have either concordant or discordant US features to benign cytology. Medical records and imaging studies were reviewed for final cytopathology results and outcomes during follow-up.
  
  
  RESULTS
  Among the 22 nodules, 17 nodules were reviewed. Fifteen of 17 nodules were malignant, and 2 were benign. The benign nodules were confirmed as adenomatous hyperplasia with underlying lymphocytic thyroiditis and a fibrotic nodule with dense calcification. Thirteen of the 15 malignant nodules had 2 or more suspicious US features, and all 15 nodules were considered to have discordant cytology considering suspicious US features. Five nodules had been followed with US or US-FNA without resection, and did not show change in size or US features on follow-up US examinations.
  
  
  CONCLUSIONS
  BRAF(V600E) mutation analysis is a highly sensitive diagnostic tool in the diagnosis of papillary thyroid carcinomas. In the management of thyroid nodules with benign cytology but positive BRAF(V600E) mutation, thyroidectomy should be considered in nodules which have 2 or more suspicious US features and are considered discordant on image-cytology correlation.
authors.affiliation: Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Soo-Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kwak
authors.affiliation: Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Korea.
authors.forename: Hee Jung
authors.initials: HJ
authors.lastname: Moon
authors.affiliation: Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Yonsei University, College of Medicine, Seoul, Korea. Electronic address: lvjenny@yuhs.ac.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution; D044963:Biopsy, Fine-Needle / Q000379:methods; D003581:Cytodiagnosis; D004252:DNA Mutational Analysis / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction / Q000706:statistics & numerical data; D012189:Retrospective Studies; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics* / Q000601:surgery; D013965:Thyroidectomy; D014463:Ultrasonography
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf