title: Contribution of molecular testing to thyroid fine-needle aspiration cytology of "follicular lesion of undetermined significance/atypia of undetermined significance".
abstract: BACKGROUND
  "Follicular lesion of undetermined significance/atypia of undetermined significance" is a heterogeneous category of cases that cannot be classified into 1 of the other established categories. The use of ancillary molecular studies has not been widely explored for this diagnosis.
  
  
  METHODS
  All thyroid cytology cases diagnosed as follicular lesion of undetermined significance/atypia of undetermined significance were retrieved from April 2007 to December 2008. During this time period, samples were collected routinely at the time of aspiration for cytologic and molecular studies. Analysis for BRAF and RAS gene mutations and RET/PTC and PAX8/PPARgamma gene rearrangements were performed and correlated with the cytologic features and surgical pathology outcome.
  
  
  RESULTS
  From a total of 513 follicular lesion of undetermined significance/atypia of undetermined significance cases identified, 455 had adequate molecular results. Of these, 117 cases had cytologic-histologic correlation. In this group, 35 (29.9%) cases had a neoplastic outcome and 20 (17.1%) cases from 19 patients were carcinoma. Positive molecular results were found in 12 cases, all of which were papillary carcinoma. There were no false-positive molecular results. In correlating the molecular results with surgical pathology outcome, we found that the cancer probability for follicular lesion of undetermined significance/atypia of undetermined significance cases with molecular alteration was 100%, while the probability for follicular lesion of undetermined significance/atypia of undetermined significance cases without molecular alteration was 7.6% (P < .001).
  
  
  CONCLUSIONS
  By cytomorphology alone, follicular lesion of undetermined significance/atypia of undetermined significance specimens represent cases that are intermediate in risk between the benign and "suspicious for follicular neoplasm" categories. Although not all papillary carcinoma cases are detected by molecular testing, a positive molecular test result is very helpful in refining follicular lesion of undetermined significance/atypia of undetermined significance cases into high-risk and low-risk categories.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center-Presbyterian, Pittsburgh, Pennsylvania 15213, USA. ohorinp@upmc.edu
authors.forename: N Paul
authors.initials: NP
authors.lastname: Ohori
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.forename: Karen E
authors.initials: KE
authors.lastname: Schoedel
authors.forename: Shane O
authors.initials: SO
authors.lastname: LeBeau
authors.forename: Steven P
authors.initials: SP
authors.lastname: Hodak
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.forename: Sally E
authors.initials: SE
authors.lastname: Carty
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Ogilvie
authors.forename: Linwah
authors.initials: L
authors.lastname: Yip
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D044963:Biopsy, Fine-Needle; D003937:Diagnosis, Differential; D011905:Genes, ras / Q000235:genetics; D005821:Genetic Techniques; D006801:Humans; D009154:Mutation / Q000235:genetics; D000072636:PAX8 Transcription Factor; D047495:PPAR gamma / Q000235:genetics; D051761:Paired Box Transcription Factors / Q000235:genetics; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D013964:Thyroid Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology*
chemical_list: D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D047495:PPAR gamma; D051761:Paired Box Transcription Factors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf