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Introducing interpretability and reasoning into Multiple Instance Learning (MIL) methods for Whole Slide Image (WSI) analysis is challenging given the complexity of gigapixel slides. Traditionally MIL interpretability is limited to identifying salient regions deemed pertinent for downstream tasks offering little insight to the end-user (pathologist) regarding the rationale behind these selections. To address this we propose Self-Interpretable MIL (SI-MIL) a method intrinsically designed for interpretability from the very outset. SI-MIL employs a deep MIL framework to guide an interpretable branch grounded on handcrafted pathological features facilitating linear predictions. Beyond identifying salient regions SI-MIL uniquely provides feature-level interpretations rooted in pathological insights for WSIs. Notably SI-MIL with its linear prediction constraints challenges the prevalent myth of an inevitable trade-off between model interpretability and performance demonstrating competitive results compared to state-of-the-art methods on WSI-level prediction tasks across three cancer types. In addition we thoroughly benchmark the local- and global-interpretability of SI-MIL in terms of statistical analysis a domain expert study and desiderata of interpretability namely user-friendliness and faithfulness. 

In digital pathology, the spatial context of cells is important for cell classification, cancer diagnosis and prognosis. To model such complex cell context, however, is challenging. Cells form different mixtures, lineages, clusters and holes. To model such structural patterns in a learnable fashion, we introduce several mathematical tools from spatial statistics and topological data analysis. We incorporate such structural descriptors into a deep generative model as both conditional inputs and a differentiable loss. This way, we are able to generate high quality multi-class cell layouts for the first time. We show that the topology-rich cell layouts can be used for data augmentation and improve the performance of downstream tasks such as cell classification.