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

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.