title: 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.
abstract: BACKGROUND
  Preoperative B-type Raf kinase Val600Glu mutation, or BRAF(V600E), analysis has been proposed as a tool to guide initial surgery for indeterminate thyroid nodules. This study sought to determine if cytologic markers of malignancy are associated with the BRAF(V600E) mutation and if preoperative BRAF(V600E) testing would alter the initial management of patients with indeterminate nodules.
  
  
  METHODS
  Patients who underwent surgery for a thyroid nodule between 2003 and 2012 at a tertiary care center were prospectively enrolled. Stored nodule samples were retrospectively genotyped for the BRAF(V600E) mutation. BRAF(V600E) status, demographics, cytologic and histopathologic findings, and choice of initial surgery were examined.
  
  
  RESULTS
  A total of 960 patients were enrolled, of which 310 (32%) had an indeterminate nodule. The BRAF(V600E) mutation was identified in 13 patients (4%), 12 of whom had either cytologic atypia or were Bethesda category V. Three percent of Bethesda category III or IV nodules that were malignant harbored the mutation compared with 42% of Bethesda category V malignancies. Nuclear grooves (P = .030), pseudoinclusions (P < .001), and oval nuclei (P = .022) were all more common among BRAF(V600E) mutants. The sensitivities of using BRAF testing alone, cytologic atypia/Bethesda category V classification, or both, were 15%, 73%, and 76%, respectively. Twelve of the 13 BRAF(V600E) mutants had total thyroidectomies initially due to worrisome cytologic features, and therefore the initial management of only one patient would have been altered if BRAF(V600E) testing had been performed preoperatively.
  
  
  CONCLUSIONS
  Preoperative mutation screening for BRAF(V600E) does not meaningfully improve risk stratification and is unlikely to alter the initial management of patients with indeterminate nodules.
authors.affiliation: Department of Surgery, New York Presbyterian Hospital-Weill Cornell Medical College, New York, New York, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Kleiman
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sporn
authors.forename: Toni
authors.initials: T
authors.lastname: Beninato
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Crowley
authors.forename: Anvy
authors.initials: A
authors.lastname: Nguyen
authors.forename: Alessia
authors.initials: A
authors.lastname: Uccelli
authors.forename: Theresa
authors.initials: T
authors.lastname: Scognamiglio
authors.forename: Rasa
authors.initials: R
authors.lastname: Zarnegar
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fahey
mesh_terms: D044963:Biopsy, Fine-Needle; D003584:Cytological Techniques; D055088:Early Detection of Cancer; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012307:Risk Factors; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology / Q000601:surgery*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf