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. 2013 Jan;137(1):32-40.
doi: 10.5858/arpa.2012-0033-OA. Epub 2012 May 14.

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

Juneko E Grilley-Olson  1 , D Neil Hayes, Dominic T Moore, Kevin O Leslie, Matthew D Wilkerson, Bahjat F Qaqish, Michele C Hayward, Christopher R Cabanski, Xiaoying Yin, Mark A Socinski, Thomas E Stinchcombe, Leigh B Thorne, Timothy Craig Allen, Peter M Banks, Mary B Beasley, Alain C Borczuk, Philip T Cagle, Rebecca Christensen, Thomas V Colby, Georgean G Deblois, Göran Elmberger, Paolo Graziano, Craig F Hart, Kirk D Jones, Diane M Maia, C Ryan Miller, Keith V Nance, William D Travis, William K Funkhouser
Affiliations

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

Juneko E Grilley-Olson et al. Arch Pathol Lab Med. 2013 Jan.

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 prevalence 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.

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Conflict of interest statement

The authors have no relevant financial interest in the products or companies described in this article.

Figures

Figure 1
Figure 1
Pathologist agreement for hematoxylin-eosin diagnosis of squamous versus non-squamous carcinoma. Abbreviations: All, all participant pathologists; Q1, first quartile; Q2, second quartile; Q3, third quartile; Q4, fourth quartile.
Figure 2
Figure 2
Each column of the figure corresponds to 1 of the 96 hematoxylin-eosin (H&E) slides. The top row shows study pathologist consensus (the majority) diagnosis. Average confidence and request for immunohistochemical stains across all reviewers are plotted as a function of the slides. Diagnosis distribution represents a heat map of the fraction of times any given 10 diagnostic-class (10DC) diagnosis was made for each of the 96 slides. The bottom 2 rows show the original pathologic diagnosis and the original neoplastic grade.
See this image and copyright information in PMC

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