Slot-Mixup with Subsampling: A Simple Regularization for WSI Classification

Whole slide image (WSI) classification requires repetitive zoom-in and out for pathologists, as only small portions of the slide may be relevant to detecting cancer. Due to the lack of patch-level labels, multiple instance learning (MIL) is a common practice for training a WSI classifier. One of the challenges in MIL for WSIs is the weak supervision coming only from the slide-level labels, often resulting in severe overfitting. In response, researchers have considered adopting patch-level augmentation or applying mixup augmentation, but their applicability remains unverified. Our approach augments the training dataset by sampling a subset of patches in the WSI without significantly altering the underlying semantics of the original slides. Additionally, we introduce an efficient model (Slot-MIL) that organizes patches into a fixed number of slots, the abstract representation of patches, using an attention mechanism. We empirically demonstrate that the subsampling augmentation helps to make more informative slots by restricting the over-concentration of attention and to improve interpretability. Finally, we illustrate that combining our attention-based aggregation model with subsampling and mixup, which has shown limited compatibility in existing MIL methods, can enhance both generalization and calibration. Our proposed methods achieve the state-of-the-art performance across various benchmark datasets including class imbalance and distribution shifts.