Abstract

Whole slide image (WSI) classification is a crucial component in automated pathology analysis. Due to the inherent challenges of high-resolution WSIs and the absence of patch-level labels, most of the proposed methods follow the multiple instance learning (MIL) formulation. While MIL has been equipped with excellent instance feature extractors and aggregators, it is prone to learn spurious associations that undermine the performance of the model. For example, relying solely on color features may lead to erroneous diagnoses due to spurious associations between the disease and the color of patches. To address this issue, we develop a causal MIL framework for WSI classification, effectively distinguishing between causal and spurious associations. Specifically, we use the expectation of the intervention P(Y | do(X)) for bag prediction rather than the traditional likelihood P(Y | X). By applying the front-door adjustment, the spurious association is effectively blocked, where the intervened mediator is aggregated from patch-level features. We evaluate our proposed method on two publicly available WSI datasets, Camelyon16 and TCGA-NSCLC. Our causal MIL framework shows outstanding performance and is plug-and-play, seamlessly integrating with various feature extractors and aggregators.

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