Andreas Mock

Yanqing Luo, Julius Hense, Niklas Prenißl et al.

Explanations of multiple instance learning (MIL) models are widely used for validation and discovery in digital histopathology. Existing methods primarily rely on heatmaps that highlight influential regions but do not explain how evidence from different tissue regions is combined to produce a prediction. This limits interpretability, especially when decisions depend on interactions between tissue features. We introduce Symbolic explainable MIL (Symb-xMIL), a post-hoc explanation framework that quantifies how a MIL model's behavior aligns with human-readable decision rules, expressed as logical relationships (e.g., AND, OR, NOT) between input features. These alignment scores reveal semantic patterns underlying the model's predictions. We evaluate Symb-xMIL on synthetic and real-world histopathology datasets. On synthetic MIL data, Symb-xMIL reliably recovers ground-truth logical rules. In a clinical tumor detection task, the best-aligned rules uncover heterogeneous decision patterns and expose hidden model errors. On an HPV-prediction task on TCGA-HNSCC, a cohort of head and neck cancer, our framework refines patient survival stratification beyond HPV status with potential clinical relevance. Overall, Symb-xMIL extends MIL explainability beyond visual attribution toward structured, rule-based reasoning, enabling more transparent and semantically grounded interpretation of model predictions.

Julius Hense, Mina Jamshidi Idaji, Oliver Eberle et al.

Multiple instance learning (MIL) is an effective and widely used approach for weakly supervised machine learning. In histopathology, MIL models have achieved remarkable success in tasks like tumor detection, biomarker prediction, and outcome prognostication. However, MIL explanation methods are still lagging behind, as they are limited to small bag sizes or disregard instance interactions. We revisit MIL through the lens of explainable AI (XAI) and introduce xMIL, a refined framework with more general assumptions. We demonstrate how to obtain improved MIL explanations using layer-wise relevance propagation (LRP) and conduct extensive evaluation experiments on three toy settings and four real-world histopathology datasets. Our approach consistently outperforms previous explanation attempts with particularly improved faithfulness scores on challenging biomarker prediction tasks. Finally, we showcase how xMIL explanations enable pathologists to extract insights from MIL models, representing a significant advance for knowledge discovery and model debugging in digital histopathology. Codes are available at: https://github.com/bifold-pathomics/xMIL.