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Breast cancer histologic grading using digital microscopy: concordance and outcome association

Rakha, Emad A.; Aleskandarany, Mohamed; Toss, Michael S.; Green, Andrew R.; Ball, Graham; Ellis, Ian O.; Dalton, Leslie W.

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Professor of Breast Cancer Pathology

Mohamed Aleskandarany

Michael S. Toss

Graham Ball

Leslie W. Dalton


AIMS: Virtual microscopy utilising digital whole slide imaging (WSI) is increasingly used in breast pathology. Histologic grade is one of the strongest prognostic factors in breast cancer (BC). This study aims at investigating the agreement between BC grading using traditional light microscopy (LM) and digital WSI with consideration of reproducibility and impact on outcome prediction.
METHODS: A large (n=1675) well-characterised cohort of BC originally graded by LM was re-graded using WSI. Two separate virtual-based grading sessions (V1 and V2) were performed with a 3-month washout period. Outcome was assessed using BC-specific and distant metastasis-free survival.
RESULTS: The concordance between LM grading and WSI was strong (LM/WSI Cramer's V: V1=0.576, and V2=0.579). The agreement regarding grade components was as follows: tubule formation=0.538, pleomorphism=0.422?and mitosis=0.514. Greatest discordance was observed between adjacent grades, whereas high/low grade discordance was uncommon (1.5%). The intraobserver agreement for the two WSI sessions was substantial for grade (V1/V2 Cramer's V=0.676; kappa=0.648) and grade components (Cramer's V T=0.628, p=0.573?and M=0.580). Grading using both platforms showed strong association with outcome (all p values? less than 0.001). Although mitotic scores assessed using both platforms were strongly associated with outcome, WSI tends to underestimate mitotic counts.
Conclusions Virtual microscopy is a reliable and reproducible method for assessing BC histologic grade. Regardless of the observer or assessment platform, histologic grade is a significant predictor of outcome. Continuing advances in imaging technology could potentially provide improved performance of WSI BC grading and in particular mitotic count assessment.

Journal Article Type Article
Acceptance Date Feb 12, 2018
Online Publication Date Mar 13, 2018
Publication Date Aug 30, 2018
Deposit Date Oct 12, 2018
Publicly Available Date Oct 16, 2018
Journal Journal of Clinical Pathology
Print ISSN 0021-9746
Electronic ISSN 1472-4146
Publisher BMJ Publishing Group
Peer Reviewed Peer Reviewed
Volume 71
Issue 8
Pages 680-686
Keywords Pathology and Forensic Medicine; General Medicine
Public URL
Publisher URL


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