# Cluster-Level Sparse Multi-Instance Learning for Whole-Slide Images

arXiv: https://arxiv.org/abs/2509.11034 · HTML: https://mlsanity.com/paper/2509.11034/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 22 of its 54 references that are in the map.
- First posted on arXiv 14 Sep 2025.

## Builds on (most cited first, 22 of 22)

- [Deep Sets](https://mlsanity.com/paper/1703.06114/) (2017)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Dual-stream Multiple Instance Learning Network for Whole Slide Image Classification with Self-supervised Contrastive Learning](https://mlsanity.com/paper/2011.08939/) (2020)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [Adaptive Prototype Learning and Allocation for Few-Shot Segmentation](https://mlsanity.com/paper/2104.01893/) (2021)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Multiple Instance Learning: A Survey of Problem Characteristics and Applications](https://mlsanity.com/paper/1612.03365/) (2016)
- [AdaptIS: Adaptive Instance Selection Network](https://mlsanity.com/paper/1909.07829/) (2019)
- [Multiple Instance Learning for Digital Pathology: A Review on the State-of-the-Art, Limitations & Future Potential](https://mlsanity.com/paper/2206.04425/) (2022)
- [Weakly Supervised Object Localization with Multi-fold Multiple Instance Learning](https://mlsanity.com/paper/1503.00949/) (2015)
- [Classification and Disease Localization in Histopathology Using Only Global Labels: A Weakly-Supervised Approach](https://mlsanity.com/paper/1802.02212/) (2018)
- [AdvMIL: Adversarial Multiple Instance Learning for the Survival Analysis on Whole-Slide Images](https://mlsanity.com/paper/2212.06515/) (2022)
- [Rethinking Multiple Instance Learning for Whole Slide Image Classification: A Good Instance Classifier is All You Need](https://mlsanity.com/paper/2307.02249/) (2023)
- [Pseudo-Bag Mixup Augmentation for Multiple Instance Learning-Based Whole Slide Image Classification](https://mlsanity.com/paper/2306.16180/) (2023)
- [HMIL: Hierarchical Multi-Instance Learning for Fine-Grained Whole Slide Image Classification](https://mlsanity.com/paper/2411.07660/) (2024)
- [AEM: Attention Entropy Maximization for Multiple Instance Learning based Whole Slide Image Classification](https://mlsanity.com/paper/2406.15303/) (2024)
- [Advances in Multiple Instance Learning for Whole Slide Image Analysis: Techniques, Challenges, and Future Directions](https://mlsanity.com/paper/2408.09476/) (2024)
- [Multiple Instance Learning Convolutional Neural Networks for Object Recognition](https://mlsanity.com/paper/1610.03155/) (2016)
- [Multi-Instance Partial-Label Learning with Margin Adjustment](https://mlsanity.com/paper/2501.12597/) (2025)
- [Multiple Instance Learning with random sampling for Whole Slide Image Classification](https://mlsanity.com/paper/2403.05351/) (2024)
- [Rethinking Attention-Based Multiple Instance Learning for Whole-Slide Pathological Image Classification: An Instance Attribute Viewpoint](https://mlsanity.com/paper/2404.00351/) (2024)

## Abstract (arXiv)

Multi-Instance Learning (MIL) is pivotal for analyzing complex, weakly labeled datasets, such as whole-slide images (WSIs) in computational pathology, where bags comprise unordered collections of instances with sparse diagnostic relevance. Traditional MIL approaches, including early statistical methods and recent attention-based frameworks, struggle with instance redundancy and lack explicit mechanisms for discarding non-informative instances, limiting their robustness and interpretability. We propose Cluster-level Sparse MIL (csMIL), a novel framework that integrates global-local instance clustering, within-cluster attention, and cluster-level sparsity induction to address these challenges. Our csMIL first performs global clustering across all bags to establish K cluster centers, followed by local clustering within each bag to assign cluster labels. Attention scores are computed within each cluster, and sparse regularization is applied to cluster weights, enabling the selective retention of diagnostically relevant clusters while discarding irrelevant ones. This approach enhances robustness to noisy instances, improves interpretability by identifying critical regions, and reduces computational complexity. Theoretical analysis demonstrates that csMIL requires O(s log K) bags to recover s relevant clusters, aligning with compressed sensing principles. Empirically, csMIL achieves state-of-the-art performance on two public histopathology benchmarks (CAMELYON16, TCGA-NSCLC).