AdaptMIL: Domain Adaptation for Multiple Instance Learning in Digital Pathology

Pathology foundation models (PFMs) have advanced rapidly in recent years and support training classifiers for a range of histopathology tasks. However, their robustness across hospitals remains limited: performance often degrades when training a classifier on data from one hospital and evaluating it on another target hospital. We address this challenge by fine-tuning PFMs with a local maximum mean discrepancy (LMMD) objective that applies to two settings: domain adaptation, where unlabeled target-hospital data is available, and domain generalization, where target-hospital data is unavailable at all. Experiments at both the patch- and slide-level show consistent improvements across multiple PFMs and tasks.

Multiple instance learning (MIL) has become the main paradigm for whole-slide image (WSI) analysis in computational pathology. However, existing MIL aggregators are still typically trained from scratch for each downstream task, relying on limited slide-level labels to learn both aggregation mechanisms and downstream discriminative representations simultaneously. As a result, they often suffer from unstable optimization, overfitting, and limited transferability. Similar to pretrained ResNet and Vision Transformer models in natural image learning, MIL also requires reusable pretrained initialization. However, high-quality slide-level pretraining data remain scarce, and MIL models are usually lightweight and weakly supervised, making large-scale pretraining difficult in practice. To address this challenge, we propose a distillation-based pretraining framework for MIL, which leverages two slide-level foundation models, TITAN and CARE, as teachers to transfer their representational knowledge into a diverse set of MIL architectures. To effectively balance supervision from different teachers, we further introduce an angular dispersion normalized distillation loss. The distilled weights are then used as initialization for downstream adaptation. We conduct systematic evaluations on 15 benchmark datasets under both linear probing and full-parameter fine-tuning, and further validate its advantages in few-shot scenarios. Experimental results show that pretraining generally improves MIL aggregators over from scratch training, especially in linear-probing and few-shot settings, while maintaining the computational efficiency of lightweight MIL models. Code is available at https://github.com/fu0201/MIL_Pretrained.

Attention-based multiple instance learning (ABMIL) using pathology foundation model embeddings is effective for slide-level tasks, but exhaustive inference requires applying a large image encoder to every foreground tile despite the subsequent attention distribution often concentrating over a small subset of informative regions. We introduce ADMIL (Attention-Distilled Multiple Instance Learning), a selective-compute framework that distills an ABMIL teacher's attention into a lightweight tile-selection model, PriorNet. Using an EfficientNet architecture, PriorNet learns the teacher attention distribution from raw tile pixels with KL divergence; at inference, it scores the foreground pool, selects the top-K tiles, and invokes the expensive foundation model only on that subset before a selected-bag ABMIL student predicts the slide label. Across BRACS, PANDA, and CAMELYON16, ADMIL matches full-teacher headline performance at K=4, 8, and 128 tiles, respectively, avoiding >98% of foundation model (Virchow2) tile embeddings and model inference FLOPs. Random and teacher-attention oracle controls show that this result depends on task-relevant selection rather than tile-count reduction alone. Quantitative and qualitative analyses suggest that PriorNet recovers the teacher's tile ordering with high fidelity while focusing on task-relevant morphological regions. ADMIL shows that nearly all expensive tile encodings can be removed without sacrificing slide-level performance, providing a potential path for more efficient deployment in clinical settings where latency and compute costs are key considerations.