# Towards Histopathological Stain Invariance by Unsupervised Domain Augmentation using Generative Adversarial Networks

arXiv: https://arxiv.org/abs/2012.12413 · HTML: https://mlsanity.com/paper/2012.12413/

## Key facts

- Cited by 17 papers in the map (data through 14 Oct 2026).
- First posted on arXiv 22 Dec 2020.

## Built on by (most cited first, 17 of 17)

- [Domain Generalization in Computational Pathology: Survey and Guidelines](https://mlsanity.com/paper/2310.19656/) (2023)
- [Test-time image-to-image translation ensembling improves out-of-distribution generalization in histopathology](https://mlsanity.com/paper/2206.09769/) (2022)
- [Improving Unsupervised Stain-To-Stain Translation using Self-Supervision and Meta-Learning](https://mlsanity.com/paper/2112.08837/) (2021)
- [A comparative evaluation of image-to-image translation methods for stain transfer in histopathology](https://mlsanity.com/paper/2303.17009/) (2023)
- [H&E-adversarial network: a convolutional neural network to learn stain-invariant features through Hematoxylin & Eosin regression](https://mlsanity.com/paper/2201.06329/) (2022)
- [CLASS-M: Adaptive stain separation-based contrastive learning with pseudo-labeling for histopathological image classification](https://mlsanity.com/paper/2312.06978/) (2023)
- [MultiPathGAN: Structure Preserving Stain Normalization using Unsupervised Multi-domain Adversarial Network with Perception Loss](https://mlsanity.com/paper/2204.09782/) (2022)
- [Towards Measuring Domain Shift in Histopathological Stain Translation in an Unsupervised Manner](https://mlsanity.com/paper/2205.04368/) (2022)
- [HistoStarGAN: A Unified Approach to Stain Normalisation, Stain Transfer and Stain Invariant Segmentation in Renal Histopathology](https://mlsanity.com/paper/2210.09798/) (2022)
- [Standardized CycleGAN training for unsupervised stain adaptation in invasive carcinoma classification for breast histopathology](https://mlsanity.com/paper/2301.13128/) (2023)
- [A Laplacian Pyramid Based Generative H&E Stain Augmentation Network](https://mlsanity.com/paper/2305.14301/) (2023)
- [Resource Efficient Multi-stain Kidney Glomeruli Segmentation via Self-supervision](https://mlsanity.com/paper/2412.15389/) (2024)
- [Advancing Histopathology with Deep Learning Under Data Scarcity: A Decade in Review](https://mlsanity.com/paper/2410.19820/) (2024)
- [Stain Consistency Learning: Handling Stain Variation for Automatic Digital Pathology Segmentation](https://mlsanity.com/paper/2311.06552/) (2023)
- [HIEGNet: A Heterogenous Graph Neural Network Including the Immune Environment in Glomeruli Classification](https://mlsanity.com/paper/2506.02542/) (2025)
- [Shortcut Learning in Glomerular AI: Adversarial Penalties Hurt, Entropy Helps](https://mlsanity.com/paper/2604.07936/) (2026)
- [DSA-CycleGAN: A Domain Shift Aware CycleGAN for Robust Multi-Stain Glomeruli Segmentation](https://mlsanity.com/paper/2604.18368/) (2026)

## Abstract (arXiv)

The application of supervised deep learning methods in digital pathology is limited due to their sensitivity to domain shift. Digital Pathology is an area prone to high variability due to many sources, including the common practice of evaluating several consecutive tissue sections stained with different staining protocols. Obtaining labels for each stain is very expensive and time consuming as it requires a high level of domain knowledge. In this article, we propose an unsupervised augmentation approach based on adversarial image-to-image translation, which facilitates the training of stain invariant supervised convolutional neural networks. By training the network on one commonly used staining modality and applying it to images that include corresponding, but differently stained, tissue structures, the presented method demonstrates significant improvements over other approaches. These benefits are illustrated in the problem of glomeruli segmentation in seven different staining modalities (PAS, Jones H&E, CD68, Sirius Red, CD34, H&E and CD3) and analysis of the learned representations demonstrate their stain invariance.