RPMIL: Rethinking Uncertainty-Aware Probabilistic Multiple Instance Learning for Whole Slide Pathology Diagnosis

Abstract

Whole slide images (WSIs) are gigapixel digital scans of traditional pathology slides, offering substantial support for cancer diagnosis. Current multiple instance learning (MIL) methods for WSIs typically extract instance features and aggregate these into a single bag feature for prediction. We observe that these MIL methods rely on point estimation, where each bag is mapped to a deterministic embedding. Such MIL methods based on point estimation fail to capture the full spectrum of data variability due to the reliance on fixed embedding, especially when the number of trainable bags is limited. In this paper, we rethink probabilistic modeling in MIL and propose RPMIL, an uncertainty-aware probabilistic MIL method for whole slide pathology diagnosis. RPMIL learns a probabilistic aggregator to consolidate instance features into dynamic bag feature distributions instead of a deterministic bag feature. Specifically, we employ a variational autoencoder approach to compress multiple instance features into a low-dimension space with probabilistic representation and obtain the bag feature distribution formulated by the mean and variance. Furthermore, we drive the prediction by jointly leveraging the instance feature distribution and bag feature distribution. We evaluate the WSI classification performance on two public datasets: Camelyon16 and TCGA-NSCLC. Extensive experiments demonstrate that our method surpasses point estimation methods in MIL, achieving state-of-the-art levels.