Bag-based Multiple Instance Learning (MIL) approaches have emerged as the mainstream methodology for Whole Slide Image (WSI) classification. However, most existing methods adopt a segmented training strategy, which first extracts features using a pre-trained feature extractor and then aggregates these features through MIL. This segmented training approach leads to insufficient collaborative optimization between the feature extraction network and the MIL network, preventing end-to-end joint optimization and thereby limiting the overall performance of the model. Additionally, conventional methods typically extract features from all patches of fixed size, ignoring the multi-scale observation characteristics of pathologists. This not only results in significant computational resource waste when tumor regions represent a minimal proportion (as in the Camelyon16 dataset) but may also lead the model to suboptimal solutions. To address these limitations, this paper proposes an end-to-end multi-scale WSI classification framework that integrates multi-scale feature extraction with multiple instance learning. Specifically, our approach includes: (1) a semantic feature filtering module to reduce interference from non-lesion areas; (2) a multi-scale feature extraction module to capture pathological information at different levels; and (3) a multi-scale fusion MIL module for global modeling and feature integration. Through an end-to-end training strategy, we simultaneously optimize both the feature extractor and MIL network, ensuring maximum compatibility between them. Experiments were conducted on three cross-center datasets (DigestPath2019, BCNB, and UBC-OCEAN). Results demonstrate that our proposed method outperforms existing state-of-the-art approaches in terms of both accuracy (ACC) and AUC metrics.

Uncertainty estimation (UE), as an effective means of quantifying predictive uncertainty, is crucial for safe and reliable decision-making, especially in high-risk scenarios. Existing UE schemes usually assume that there are completely-labeled samples to support fully-supervised learning. In practice, however, many UE tasks often have no sufficiently-labeled data to use, such as the Multiple Instance Learning (MIL) with only weak instance annotations. To bridge this gap, this paper, for the first time, addresses the weakly-supervised issue of Multi-Instance UE (MIUE) and proposes a new baseline scheme, Multi-Instance Residual Evidential Learning (MIREL). Particularly, at the fine-grained instance UE with only weak supervision, we derive a multi-instance residual operator through the Fundamental Theorem of Symmetric Functions. On this operator derivation, we further propose MIREL to jointly model the high-order predictive distribution at bag and instance levels for MIUE. Extensive experiments empirically demonstrate that our MIREL not only could often make existing MIL networks perform better in MIUE, but also could surpass representative UE methods by large margins, especially in instance-level UE tasks. Our source code is available at https://github.com/liupei101/MIREL.