# ProtoPur: Prototype-Purity Pseudo-Labeling for Weakly Supervised Instance Learning in Pathology

arXiv: https://arxiv.org/abs/2610.15669 · HTML: https://mlsanity.com/paper/2610.15669/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 9 of its 32 references that are in the map.
- First posted on arXiv 11 Oct 2026.

## Builds on (most cited first, 9 of 9)

- [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)
- [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)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [BRACS: A Dataset for BReAst Carcinoma Subtyping in H&E Histology Images](https://mlsanity.com/paper/2111.04740/) (2021)
- [Multiple Instance Learning Framework with Masked Hard Instance Mining for Whole Slide Image Classification](https://mlsanity.com/paper/2307.15254/) (2023)
- [Bi-directional Weakly Supervised Knowledge Distillation for Whole Slide Image Classification](https://mlsanity.com/paper/2210.03664/) (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)

## Abstract (arXiv)

Weak bag-level labels are widely available in computational pathology, whereas reliable instance-level annotations for whole-slide images remain expensive and ambiguous. Weakly supervised multiple instance learning (MIL) achieves strong bag-level classification, but instance-level supervision from attention scores, model predictions, negative bags, or spatial refinement may fail to identify class-specific local evidence. We propose ProtoPur, a prototype-purity pseudo-labeling method for weakly supervised instance-level learning in pathology whole-slide images. ProtoPur estimates class-balanced local purity over prototype regions constructed from frozen foundation-model features, and assigns pseudo-labels to high-purity regions strongly associated with a target class. This purity-first design separates class-specific evidence from negative or shared morphology, with coverage used only to ensure sufficient pseudo-label assignment. We provide a PAC-style analysis showing that the risk of an instance classifier trained with ProtoPur pseudo-labels can be decomposed into a standard uniform-convergence term and a ProtoPur-specific pseudo-label noise term, comprising selected-region mismatch and a coverage residual. Experiments on three public whole-slide image datasets with two pathology foundation encoders show that ProtoPur consistently improves instance-level performance across multiple MIL backbones while maintaining competitive bag-level performance. Pseudo-label quality comparisons on two public datasets further demonstrate that prototype-purity selection provides stronger instance supervision. These results suggest that the foundation-model features contain exploitable instance-level supervision signals, and ProtoPur is a way to reveal and use these signals from weak bag labels without requiring dense instance annotations.