From Bill Funkhouser and colleagues: 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

http://www.ncbi.nlm.nih.gov/pubmed/22583114

Arch Pathol Lab Med. 2012 May 14. [Epub ahead of print]

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.

Grilley-Olson JE, Hayes DN, Moore DT, Leslie KO, Wilkerson MD, Qaqish BF, Hayward MC, Cabanski CR, Yin X, Socinski MA,Stinchcombe TE, Thorne LB, Allen TC, Banks PM, Beasley MB, Borczuk AC, Cagle PT, Christensen R, Colby TV, Deblois GG,Elmberger G, Graziano P, Hart CF, Jones KD, Maia DM, Miller CR, Nance KV, Travis WD, Funkhouser WK.

Abstract

Context.

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 prealence of activating epidermal growth factor receptor mutations. Objectives.-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. 

Design.

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.