title: BRAF mutation testing of thyroid fine-needle aspiration specimens enhances the predictability of malignancy in thyroid follicular lesions of undetermined significance.
abstract: OBJECTIVE
  The Bethesda 2007 Thyroid Cytology Classification defines atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) as a heterogeneous category of cases that are neither convincingly benign nor sufficiently atypical for a diagnosis of follicular neoplasm or suspicious for malignancy. At our institution, we refer to these cases as 'indeterminate' and they are further subclassified into two categories. BRAF mutation occurs in 40-60% of papillary thyroid carcinoma (PTC). In this study, we examined cases in the AUS/FLUS category in correlation with BRAF mutation analysis and surgical pathology outcome.
  
  
  METHODS
  Thyroid fine-needle aspiration (FNA) cytology specimens interpreted as 'indeterminate' were selected from our files, and available remnants of thin-layer processed specimens were used for BRAF mutation analysis. Surgical pathology reports were reviewed for the final outcomes in these patients.
  
  
  RESULTS
  Of the 84 indeterminate cases with BRAF mutation analysis, only 49 had follow-up with surgical intervention. Sixteen cases had BRAF mutation. All of the BRAF-positive cases had a final diagnosis of PTC.
  
  
  CONCLUSIONS
  The sensitivity and specificity of BRAF mutation in detecting PTC in FNA specimens with indeterminate diagnosis was 59.3 and 100%, respectively, while the positive and negative predictive values were 100 and 65.6%, respectively. The limited data supports the use of BRAF mutation analysis to predict the risk of malignancy in patients with indeterminate thyroid FNAs.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Conn., USA. adebowale.adeniran@yale.edu
authors.forename: Adebowale J
authors.initials: AJ
authors.lastname: Adeniran
authors.forename: Pei
authors.initials: P
authors.lastname: Hui
authors.forename: David C
authors.initials: DC
authors.lastname: Chhieng
authors.forename: Manju L
authors.initials: ML
authors.lastname: Prasad
authors.forename: Kevin
authors.initials: K
authors.lastname: Schofield
authors.forename: Constantine
authors.initials: C
authors.lastname: Theoharis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002291:Carcinoma, Papillary; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017410:Practice Guidelines as Topic; D011237:Predictive Value of Tests; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012306:Risk; D009626:Terminology as Topic; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016606:Thyroid Nodule / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf