title: A large multicenter correlation study of thyroid nodule cytopathology and histopathology.
abstract: BACKGROUND
  Fine-needle aspiration (FNA) biopsies are the cornerstone of preoperative evaluation of thyroid nodules, but FNA diagnostic performance has varied across different studies. In the course of collecting thyroid FNA specimens for the development of a molecular diagnostic test, local cytology and both local and expert panel surgical pathology results were reviewed.
  
  
  METHODS
  Prospective FNAs were collected at 21 clinical sites. Banked FNAs were collected from two academic centers. Cytology and corresponding local and expert panel surgical pathology results were compared to each other and to a meta-review of 11 recently published U.S.-based thyroid FNA studies.
  
  
  RESULTS
  FNA diagnostic performance was comparable between the study specimens and the meta-review. Histopathology malignancy rates for prospective clinic FNAs were 34% for cytology indeterminate cases and 98% for cytology malignant cases, comparable to the figures found in the meta-review (34% and 97%, respectively). However, histopathology malignancy rates were higher for cytology benign cases in the prospective clinic FNA subcohort (11%) than in the meta-review (6%, with meta-review rates of 10% at community sites and 2% at academic centers, p < 0.0001). Resection rates for prospective clinic FNAs were also comparable to the meta-review for both cytology indeterminate cases (62% vs. 59%, respectively) and cytology malignant cases (82% vs. 81%, respectively). Surgical pathology categorical disagreement (benign vs. malignant diagnosis) was higher between local pathology and a consensus of the two expert panelists (11%) than between the two expert panelists both pre- (8%) and postconferral (3%).
  
  
  CONCLUSIONS
  Although recent guidelines for FNA biopsy and interpretation have been published, the rates of false-positive and false-negative results remain a challenge. Two-thirds of cytology indeterminate cases were benign postoperatively and may decrease with the development of an accurate molecular diagnostic test. High disagreement rates between local and expert panel histopathology diagnosis suggests that central review for surgical diagnoses should be used when developing diagnostic tests based on resected thyroid specimens.
authors.affiliation: Department of Medical and Clinical Affairs, Veracyte, Inc., South San Francisco, California 94080, USA. c.charles.wang@gmail.com
authors.forename: Chung-Che Charles
authors.initials: CC
authors.lastname: Wang
authors.forename: Lyssa
authors.initials: L
authors.lastname: Friedman
authors.forename: Giulia C
authors.initials: GC
authors.lastname: Kennedy
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
authors.forename: David L
authors.initials: DL
authors.lastname: Steward
authors.forename: Martha A
authors.initials: MA
authors.lastname: Zeiger
authors.forename: William H
authors.initials: WH
authors.lastname: Westra
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Elham
authors.initials: E
authors.lastname: Khanafshar
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fellegara
authors.forename: Juan
authors.initials: J
authors.lastname: Rosai
authors.forename: Virginia
authors.initials: V
authors.lastname: Livolsi
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lanman
mesh_terms: D044963:Biopsy, Fine-Needle / Q000379:methods*; D002277:Carcinoma; D002291:Carcinoma, Papillary; D006801:Humans; D011446:Prospective Studies; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000473:pathology; D016606:Thyroid Nodule / Q000473:pathology* / Q000601:surgery