Beyond Attention Heatmaps: How to Get Better Explanations for Multiple Instance Learning Models in Histopathology

Multiple instance learning (MIL) has enabled substantial progress in computational histopathology, where a large amount of patches from gigapixel whole slide images are aggregated into slide-level predictions. Heatmaps are widely used to validate MIL models and to discover tissue biomarkers. Yet, the validity of these heatmaps has barely been investigated. In this work, we introduce a general framework for evaluating the quality of MIL heatmaps without requiring additional labels. We conduct a large-scale benchmark experiment to assess six explanation methods across histopathology task types (classification, regression, survival), MIL model architectures (Attention-, Transformer-, Mamba-based), and patch encoder backbones (UNI2, Virchow2). Our results show that explanation quality mostly depends on MIL model architecture and task type, with perturbation ("Single"), layer-wise relevance propagation (LRP), and integrated gradients (IG) consistently outperforming attention-based and gradient-based saliency heatmaps, which often fail to reflect model decision mechanisms. We further demonstrate the advanced capabilities of the best-performing explanation methods: (i) We provide a proof-of-concept that MIL heatmaps of a bulk gene expression prediction model can be correlated with spatial transcriptomics for biological validation, and (ii) showcase the discovery of distinct model strategies for predicting human papillomavirus (HPV) infection from head and neck cancer slides. Our work highlights the importance of validating MIL heatmaps and establishes that improved explainability can enable more reliable model validation and yield biological insights, making a case for a broader adoption of explainable AI in digital pathology. Our code is provided in a public GitHub repository: https://github.com/bifold-pathomics/xMIL/tree/xmil-journal

Cat, Rat, Meow: On the Alignment of Language Model and Human Term-Similarity Judgments

Small and mid-sized generative language models have gained increasing attention. Their size and availability make them amenable to being analyzed at a behavioral as well as a representational level, allowing investigations of how these levels interact. We evaluate 32 publicly available language models for their representational and behavioral alignment with human similarity judgments on a word triplet task. This provides a novel evaluation setting to probe semantic associations in language beyond common pairwise comparisons. We find that (1) even the representations of small language models can achieve human-level alignment, (2) instruction-tuned model variants can exhibit substantially increased agreement, (3) the pattern of alignment across layers is highly model dependent, and (4) alignment based on models' behavioral responses is highly dependent on model size, matching their representational alignment only for the largest evaluated models.