Breast Cancer Prognostic Factors in the Digital Era: Comparison of Nottingham Grade using Whole Slide Images and Glass Slides

Tara M Davidson; Mara H Rendi; Paul D Frederick; Tracy Onega; Kimberly H Allison; Ezgi Mercan; Tad T Brunyé; Linda G Shapiro; Donald L Weaver; Joann G Elmore

doi:10.4103/jpi.jpi_29_18

Breast Cancer Prognostic Factors in the Digital Era: Comparison of Nottingham Grade using Whole Slide Images and Glass Slides

J Pathol Inform. 2019 Apr 3:10:11. doi: 10.4103/jpi.jpi_29_18. eCollection 2019.

Authors

Affiliations

¹ Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
² Department of Pathology, School of Medicine, University of Washington, Seattle, WA, USA.
³ Department of Community and Family Medicine, Norris Cotton Cancer Center, Geisel School of Medicine, The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth College, Hanover, NH, USA.
⁴ Department of Pathology, School of Medicine, Stanford University, Stanford, CA, USA.
⁵ Department of Computer Science and Engineering, College of Engineering, University of Washington, Seattle, WA, USA.
⁶ Department of Psychology, School of Arts and Sciences, Tufts University, Medford, MA, USA.
⁷ Department of Pathology, University of Vermont Cancer Center, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
⁸ Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.

Abstract

Background: To assess reproducibility and accuracy of overall Nottingham grade and component scores using digital whole slide images (WSIs) compared to glass slides.

Methods: Two hundred and eight pathologists were randomized to independently interpret 1 of 4 breast biopsy sets using either glass slides or digital WSI. Each set included 5 or 6 invasive carcinomas (22 total invasive cases). Participants interpreted the same biopsy set approximately 9 months later following a second randomization to WSI or glass slides. Nottingham grade, including component scores, was assessed on each interpretation, providing 2045 independent interpretations of grade. Overall grade and component scores were compared between pathologists (interobserver agreement) and for interpretations by the same pathologist (intraobserver agreement). Grade assessments were compared when the format (WSI vs. glass slides) changed or was the same for the two interpretations.

Results: Nottingham grade intraobserver agreement was highest using glass slides for both interpretations (73%, 95% confidence interval [CI]: 68%, 78%) and slightly lower but not statistically different using digital WSI for both interpretations (68%, 95% CI: 61%, 75%; P= 0.22). The agreement was lowest when the format changed between interpretations (63%, 95% CI: 59%, 68%). Interobserver agreement was significantly higher (P < 0.001) using glass slides versus digital WSI (68%, 95% CI: 66%, 70% versus 60%, 95% CI: 57%, 62%, respectively). Nuclear pleomorphism scores had the lowest inter- and intra-observer agreement. Mitotic scores were higher on glass slides in inter- and intra-observer comparisons.

Conclusions: Pathologists' intraobserver agreement (reproducibility) is similar for Nottingham grade using glass slides or WSI. However, slightly lower agreement between pathologists suggests that verification of grade using digital WSI may be more challenging.

Keywords: Digital whole slide imaging; Nottingham grade; image analysis; interobserver agreement; interobserver variability; interrater; intraobserver agreement; intrarater; kappa; reproducibility.

Abstract

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