title: Reproducibility of the WHO classification of thymomas: practical implications.
abstract: BACKGROUND
  The WHO-classification was shown to be an independent prognostic marker in some but not all retrospective studies possibly due to lack of reproducibility. We investigated the reproducibility of the WHO-classification and its prognostic implication using a large series of resected thymomas.
  
  
  METHODS
  Four independent pathologists histologically classified a surgical series of 129 thymic tumors in a blinded fashion. Fleiss' kappa-coefficient was used to assess the pathologists' overall agreement, and Cohen-Kappa to assess the agreement between two observers. Disease-related-survival (DRS) and progression-free-survival (PFS) curves were generated by Kaplan-Meier method and compared by log-rank test.
  
  
  RESULTS
  In 63/129 (48.8%) cases there was a complete agreement; in 43/129 (33.3%) cases 3/4 pathological diagnoses were identical; in 15/129 (11.6%) cases the diagnoses were identical by pair; in 8/129 (6.2%) cases three different pathological diagnoses were on record. The Kappa-correlation coefficient was only moderate (0.53). A following web review carried out on the 23 cases with at least two different diagnoses reached a complete consensus. The histotype showed a statistically significant impact on PFS and DRS in the classification provided by only two pathologists.
  
  
  CONCLUSIONS
  In this study, the agreement on WHO classification of thymomas was only moderate and this impacted on patients management. Web consensus conference on the diagnosis, more stringent diagnostic criteria or the adoption of referral diagnostic centres may substantially reduce discrepancies.
authors.affiliation: Humanitas Cancer Center, Via Manzoni 56, Rozzano, Milan, Italy.
authors.forename: P A
authors.initials: PA
authors.lastname: Zucali
authors.forename: L
authors.initials: L
authors.lastname: Di Tommaso
authors.forename: I
authors.initials: I
authors.lastname: Petrini
authors.forename: S
authors.initials: S
authors.lastname: Battista
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Merino
authors.forename: E
authors.initials: E
authors.lastname: Lorenzi
authors.forename: E
authors.initials: E
authors.lastname: Voulaz
authors.forename: F
authors.initials: F
authors.lastname: De Vincenzo
authors.forename: M
authors.initials: M
authors.lastname: Simonelli
authors.forename: M
authors.initials: M
authors.lastname: Roncalli
authors.forename: L
authors.initials: L
authors.lastname: Giordano
authors.forename: M
authors.initials: M
authors.lastname: Alloisio
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D032921:Consensus; D003245:Consensus Statements as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017410:Practice Guidelines as Topic; D011379:Prognosis; D015203:Reproducibility of Results; D013945:Thymoma / Q000145:classification* / Q000401:mortality / Q000473:pathology*; D014944:World Health Organization; D055815:Young Adult