# Self-Supervision Enhances Instance-based Multiple Instance Learning Methods in Digital Pathology: A Benchmark Study

arXiv: https://arxiv.org/abs/2505.01109 · HTML: https://mlsanity.com/paper/2505.01109/

## Key facts

- Cited by 6 papers in the map (data through 14 Oct 2026).
- Builds on 55 of its 71 references that are in the map.
- First posted on arXiv 2 May 2025.

## Builds on (most cited first, 30 of 55)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Momentum Contrast for Unsupervised Visual Representation Learning](https://mlsanity.com/paper/1911.05722/) (2019)
- [Masked Autoencoders Are Scalable Vision Learners](https://mlsanity.com/paper/2111.06377/) (2021)
- [Emerging Properties in Self-Supervised Vision Transformers](https://mlsanity.com/paper/2104.14294/) (2021)
- [Bootstrap your own latent: A new approach to self-supervised Learning](https://mlsanity.com/paper/2006.07733/) (2020)
- [Unsupervised Learning of Visual Features by Contrasting Cluster Assignments](https://mlsanity.com/paper/2006.09882/) (2020)
- [Barlow Twins: Self-Supervised Learning via Redundancy Reduction](https://mlsanity.com/paper/2103.03230/) (2021)
- [An Empirical Study of Training Self-Supervised Vision Transformers](https://mlsanity.com/paper/2104.02057/) (2021)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [iBOT: Image BERT Pre-Training with Online Tokenizer](https://mlsanity.com/paper/2111.07832/) (2021)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [Transfusion: Understanding Transfer Learning for Medical Imaging](https://mlsanity.com/paper/1902.07208/) (2019)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [Not-so-supervised: a survey of semi-supervised, multi-instance, and transfer learning in medical image analysis](https://mlsanity.com/paper/1804.06353/) (2018)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Deep neural network models for computational histopathology: A survey](https://mlsanity.com/paper/1912.12378/) (2019)
- [Multiple Instance Learning: A Survey of Problem Characteristics and Applications](https://mlsanity.com/paper/1612.03365/) (2016)
- [Patch-based Convolutional Neural Network for Whole Slide Tissue Image Classification](https://mlsanity.com/paper/1504.07947/) (2015)
- [Benchmarking Self-Supervised Learning on Diverse Pathology Datasets](https://mlsanity.com/paper/2212.04690/) (2022)
- [BRACS: A Dataset for BReAst Carcinoma Subtyping in H&E Histology Images](https://mlsanity.com/paper/2111.04740/) (2021)
- [Whole Slide Images are 2D Point Clouds: Context-Aware Survival Prediction using Patch-based Graph Convolutional Networks](https://mlsanity.com/paper/2107.13048/) (2021)
- [Revisiting Multiple Instance Neural Networks](https://mlsanity.com/paper/1610.02501/) (2016)
- [Solo-learn: A Library of Self-supervised Methods for Visual Representation Learning](https://mlsanity.com/paper/2108.01775/) (2021)
- [Interventional Bag Multi-Instance Learning On Whole-Slide Pathological Images](https://mlsanity.com/paper/2303.06873/) (2023)

## Built on by (most cited first, 6 of 6)

- [SGPMIL: Sparse Gaussian Process Multiple Instance Learning](https://mlsanity.com/paper/2507.08711/) (2025)
- [Masked Omics Modeling for Multimodal Representation Learning across Histopathology and Molecular Profiles](https://mlsanity.com/paper/2508.00969/) (2025)
- [CAPRMIL: Context-Aware Patch Representations for Multiple Instance Learning](https://mlsanity.com/paper/2512.14540/) (2025)
- [Leveraging whole slide difficulty in Multiple Instance Learning to improve prostate cancer grading](https://mlsanity.com/paper/2603.09953/) (2026)
- [Weakly Supervised Multicenter Nancy Index Scoring in Ulcerative Colitis Using Foundation Models](https://mlsanity.com/paper/2604.23706/) (2026)
- [Learning Where to Focus: Self-Supervised Multi-Scale ViTs for Histopathology](https://mlsanity.com/paper/2609.18578/) (2026)

## Abstract (arXiv)

Multiple Instance Learning (MIL) has emerged as the best solution for Whole Slide Image (WSI) classification. It consists of dividing each slide into patches, which are treated as a bag of instances labeled with a global label. MIL includes two main approaches: instance-based and embedding-based. In the former, each patch is classified independently, and then the patch scores are aggregated to predict the bag label. In the latter, bag classification is performed after aggregating patch embeddings. Even if instance-based methods are naturally more interpretable, embedding-based MILs have usually been preferred in the past due to their robustness to poor feature extractors. However, recently, the quality of feature embeddings has drastically increased using self-supervised learning (SSL). Nevertheless, many authors continue to endorse the superiority of embedding-based MIL. To investigate this further, we conduct 710 experiments across 4 datasets, comparing 10 MIL strategies, 6 self-supervised methods with 4 backbones, 4 foundation models, and various pathology-adapted techniques. Furthermore, we introduce 4 instance-based MIL methods never used before in the pathology domain. Through these extensive experiments, we show that with a good SSL feature extractor, simple instance-based MILs, with very few parameters, obtain similar or better performance than complex, state-of-the-art (SOTA) embedding-based MIL methods, setting new SOTA results on the BRACS and Camelyon16 datasets. Since simple instance-based MIL methods are naturally more interpretable and explainable to clinicians, our results suggest that more effort should be put into well-adapted SSL methods for WSI rather than into complex embedding-based MIL methods.