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Nottingham grading system is a major prognostic factor forinvasive breast carcinoma (IBC). Its determination requires the evaluation ofthe mitotic score (MS) which is subject to low intra- and inter-observerreproducibility. The MS shall be performed in the most proliferative area ofthe tumor, which determination is hard but critical. Artificial intelligencebased tools could help pathologists to detect mitosis on whole slide images(WSI). Objective: The aim of this study was to evaluate the contribution of amitosis detection algorithms pecifically developed to assist the pathologistduring the evaluation of the MS on WSI. Methods: Algorithmic mitosis detectionis a two-step process: first the algorithm detects candidate objects resemblingmitosis, then the selection is refined by a classifier. The densestmitoticregions are shown to the pathologist, then he can establish the MS withalgorithm results. For this study, three expert pathologists have determined aconsensual ground truth for MS on fifty WSI of IBC. Those slides were alsosubmitted to two readers pathologists who evaluated the MS of each slide twice,with and without the assistance of the algorithm, with a four week wash-outperiod. Interobserver reproducibility was measured by evaluating the scoresobtained with, and without assistance between two readers pathologists and wasalso measured between each reader pathologist and the expert ground truth todetermine the accuracy of the established score. Results:Baseline linearlyweighted Cohen's Kappa for interobserver agreement of MS between two readerspathologists was 0.482. Using the algorithm generated mitotic detection in WSI,the agreement score increased to 0.672. Baseline linearly weighted Cohen'sKappa for interobserver agreement of MS between each reader pathologist andexpert consensus was 0.378 and 0.457 for pathologist 1 and 2 respectively.Using the algorithm generated mitoticdetection in WSI, the agreement scoreincreased respectively to 0.629 and 0.726. Conclusion:The use of the developedalgorithm constitutes a viable approach to assist the pathologist for theevaluation of the MS of IBC on WSI. Its use makes it possible to improveinterobserver reproducibility between pathologists and the accuracy of thescore established by expert consensus. The use of such a tool constitutes a newapproach in the evaluation of the mitoticscore which could lead to an evolutionof practices.

Evaluation of the mitotic score of invasive breast carcinomas on digital slide: development and contribution of a mitosis detection algorithm