# Whole-Slide Mitosis Detection in H&E Breast Histology Using PHH3 as a Reference to Train Distilled Stain-Invariant Convolutional Networks

arXiv: https://arxiv.org/abs/1808.05896 · HTML: https://mlsanity.com/paper/1808.05896/

## Key facts

- Cited by 57 papers in the map (data through 14 Oct 2026).
- First posted on arXiv 17 Aug 2018.

## Built on by (most cited first, 30 of 57)

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- [Connect Later: Improving Fine-tuning for Robustness with Targeted Augmentations](https://mlsanity.com/paper/2402.03325/) (2024)
- [Mitosis Detection, Fast and Slow: Robust and Efficient Detection of Mitotic Figures](https://mlsanity.com/paper/2208.12587/) (2022)
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- [OMG-Net: A Deep Learning Framework Deploying Segment Anything to Detect Pan-Cancer Mitotic Figures from Haematoxylin and Eosin-Stained Slides](https://mlsanity.com/paper/2407.12773/) (2024)
- [Histopath-C: Towards Realistic Domain Shifts for Histopathology Vision-Language Adaptation](https://mlsanity.com/paper/2601.12493/) (2026)
- [MitoDet: Simple and robust mitosis detection](https://mlsanity.com/paper/2109.01485/) (2021)
- [A review of machine learning approaches, challenges and prospects for computational tumor pathology](https://mlsanity.com/paper/2206.01728/) (2022)
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## Abstract (arXiv)

Manual counting of mitotic tumor cells in tissue sections constitutes one of the strongest prognostic markers for breast cancer. This procedure, however, is time-consuming and error-prone. We developed a method to automatically detect mitotic figures in breast cancer tissue sections based on convolutional neural networks (CNNs). Application of CNNs to hematoxylin and eosin (H&E) stained histological tissue sections is hampered by: (1) noisy and expensive reference standards established by pathologists, (2) lack of generalization due to staining variation across laboratories, and (3) high computational requirements needed to process gigapixel whole-slide images (WSIs). In this paper, we present a method to train and evaluate CNNs to specifically solve these issues in the context of mitosis detection in breast cancer WSIs. First, by combining image analysis of mitotic activity in phosphohistone-H3 (PHH3) restained slides and registration, we built a reference standard for mitosis detection in entire H&E WSIs requiring minimal manual annotation effort. Second, we designed a data augmentation strategy that creates diverse and realistic H&E stain variations by modifying the hematoxylin and eosin color channels directly. Using it during training combined with network ensembling resulted in a stain invariant mitosis detector. Third, we applied knowledge distillation to reduce the computational requirements of the mitosis detection ensemble with a negligible loss of performance. The system was trained in a single-center cohort and evaluated in an independent multicenter cohort from The Cancer Genome Atlas on the three tasks of the Tumor Proliferation Assessment Challenge (TUPAC). We obtained a performance within the top-3 best methods for most of the tasks of the challenge.