title: Validation of interobserver agreement in lung cancer assessment: hematoxylin-eosin diagnostic reproducibility for non-small cell lung cancer: the 2004 World Health Organization classification and therapeutically relevant subsets.
abstract: BACKGROUND
  Precise subtype diagnosis of non-small cell lung carcinoma is increasingly relevant, based on the availability of subtype-specific therapies, such as bevacizumab and pemetrexed, and based on the subtype-specific prevalence of activating epidermal growth factor receptor mutations.
  
  
  OBJECTIVE
  To establish a baseline measure of interobserver reproducibility for non-small cell lung carcinoma diagnoses with hematoxylin-eosin for the current 2004 World Health Organization classification, to estimate interobserver reproducibility for the therapeutically relevant squamous/nonsquamous subsets, and to examine characteristics that improve interobserver reproducibility.
  
  
  METHODS
  Primary, resected lung cancer specimens were converted to digital (virtual) slides. Based on a single hematoxylin-eosin virtual slide, pathologists were asked to assign a diagnosis using the 2004 World Health Organization classification. Kappa statistics were calculated for each pathologist-pair for each slide and were summarized by classification scheme, pulmonary pathology expertise, diagnostic confidence, and neoplastic grade.
  
  
  RESULTS
  The 12 pulmonary pathology experts and the 12 community pathologists each independently diagnosed 48 to 96 single hematoxylin-eosin digital slides derived from 96 cases of non-small cell lung carcinoma resection. Overall agreement improved with simplification from the comprehensive 44 World Health Organization diagnoses (κ  =  0.25) to their 10 major header subtypes (κ  =  0.48) and improved again with simplification into the therapeutically relevant squamous/nonsquamous dichotomy (κ  =  0.55). Multivariate analysis showed that higher diagnostic agreement was associated with better differentiation, better slide quality, higher diagnostic confidence, similar years of pathology experience, and pulmonary pathology expertise.
  
  
  CONCLUSIONS
  These data define the baseline diagnostic agreement for hematoxylin-eosin diagnosis of non-small cell lung carcinoma, allowing future studies to test for improved diagnostic agreement with reflex ancillary tests.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7295, USA.
authors.forename: Juneko E
authors.initials: JE
authors.lastname: Grilley-Olson
authors.forename: D Neil
authors.initials: DN
authors.lastname: Hayes
authors.forename: Dominic T
authors.initials: DT
authors.lastname: Moore
authors.forename: Kevin O
authors.initials: KO
authors.lastname: Leslie
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Wilkerson
authors.forename: Bahjat F
authors.initials: BF
authors.lastname: Qaqish
authors.forename: Michele C
authors.initials: MC
authors.lastname: Hayward
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cabanski
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yin
authors.forename: Mark A
authors.initials: MA
authors.lastname: Socinski
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stinchcombe
authors.forename: Leigh B
authors.initials: LB
authors.lastname: Thorne
authors.forename: Timothy Craig
authors.initials: TC
authors.lastname: Allen
authors.forename: Peter M
authors.initials: PM
authors.lastname: Banks
authors.forename: Mary B
authors.initials: MB
authors.lastname: Beasley
authors.forename: Alain C
authors.initials: AC
authors.lastname: Borczuk
authors.forename: Philip T
authors.initials: PT
authors.lastname: Cagle
authors.forename: Rebecca
authors.initials: R
authors.lastname: Christensen
authors.forename: Thomas V
authors.initials: TV
authors.lastname: Colby
authors.forename: Georgean G
authors.initials: GG
authors.lastname: Deblois
authors.forename: Göran
authors.initials: G
authors.lastname: Elmberger
authors.forename: Paolo
authors.initials: P
authors.lastname: Graziano
authors.forename: Craig F
authors.initials: CF
authors.lastname: Hart
authors.forename: Kirk D
authors.initials: KD
authors.lastname: Jones
authors.forename: Diane M
authors.initials: DM
authors.lastname: Maia
authors.forename: C Ryan
authors.initials: CR
authors.lastname: Miller
authors.forename: Keith V
authors.initials: KV
authors.lastname: Nance
authors.forename: William D
authors.initials: WD
authors.lastname: Travis
authors.forename: William K
authors.initials: WK
authors.lastname: Funkhouser
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification* / Q000175:diagnosis*; D003625:Data Collection; D004801:Eosine Yellowish-(YS); D005260:Female; D006416:Hematoxylin; D006801:Humans; D020407:Internet; D008175:Lung Neoplasms / Q000145:classification* / Q000175:diagnosis*; D008297:Male; D015588:Observer Variation; D010340:Pathology, Surgical; D013194:Staining and Labeling; D014944:World Health Organization
chemical_list: D004801:Eosine Yellowish-(YS); D006416:Hematoxylin