DeCo-MIL: Debiased Counterfactual Reasoning for Long-Tailed Whole Slide Image Analysis

In weakly supervised Whole Slide Image (WSI) classification, feature extractors typically compress each image tile into a single global embedding. Consequently, slide-level aggregators are restricted to this coarse tile scale, concealing fine-grained sub-tile evidence from the attention mechanism. We introduce DI-MIL, a framework that decouples encoding context from instance granularity through decomposed instances. By clustering dense spatial tokens from a frozen foundation model within each tile, DI-MIL converts a single tile into multiple independently weighted instance embeddings. As a training-free post-encoding module, DI-MIL integrates seamlessly into existing pipelines without requiring re-encoding or downstream architectural modifications. We evaluate DI-MIL on cytopathology, a challenging testbed where sparse diagnostic signals are easily diluted within standard tiles. Across four datasets, three frozen foundation models, and two attention-based aggregators, DI-MIL demonstrates consistent efficacy, improving 67 of 72 metric-level comparisons, with the largest mean gains reaching 3.64 points under cytopathology-specific backbones. In a broader comparison against seven representative MIL baselines, DI-MIL paired with ACMIL achieves highest mean performance in 33 of 36 backbone-dataset-metric comparisons. Ablations show that direct smaller tiling inflates the extracted tile count by up to 43.3$\times$ with non-monotonic performance, whereas DI-MIL incurs zero additional image-extraction overhead while achieving the strongest overall results. These results establish instance construction as an orthogonal design dimension in MIL, supporting DI-MIL as a cost-efficient solution under sparse diagnostic evidence.

Multiple instance learning (MIL) is the standard approach for whole-slide image (WSI) classification and survival prediction, where attention-based models ag gregate patch features into slide-level predictions. These models treat attention weights as evidence for their predictions, but attention is optimized for classi fication, not for identifying which patches actually support the diagnosis. This conflation leads to three failures: selected patches are insufficient (keeping them alone drops Macro-F1 by 0.078), unnecessary (removing them barely changes the prediction), and unrecoverable (continuous attention scores disagree with discrete patch subsets used at inference). The central premise is that evidence quality should be optimized directly through explicit criteria- Sufficiency, Necessity, and Recov erability (S/N/R)- rather than inherited as a byproduct of classification. GCE-MIL is a backbone-agnostic wrapper implemented through three injection modes and three evidence components: a grounding mechanism that aligns selection with domain-specific concepts, noisy-OR coverage that acts as a differentiable proxy for interventional evidence search, and threshold-plus-repair recovery that converts continuous selectors into discrete subsets through marginal-guided repair. Across 9 backbones and 9 datasets (81 configurations), GCE-MIL improves average Macro-F1 by 0.024 and C-index by 0.014, reduces the continuous-discrete gap by 4-7, and increases complement degradation by 2-4. With optional tile prefiltering after discrete recovery, inference runs up to 5 faster while retaining 0.989 full-bag utility.

Multiple instance learning (MIL) has become a standard paradigm for whole slide image (WSI) analysis in digital pathology, as it enables slide-level prediction without dense annotations. Existing MIL methods typically rely on exhaustive extraction and encoding of high-resolution patches. However, this practice suffers from two critical limitations in real-world clinical settings: it struggles to capture global visual cues at lower magnifications, and incurs substantial computational overhead due to the massive number of high-resolution patches per slide. To address these limitations, we propose an efficient low-resolution multiple instance learning (LRMIL) framework that transfers high-resolution knowledge to low-resolution representations. LRMIL adopts a two-stage distillation strategy. First, patch-level cross-resolution distillation aligns low-resolution patch embeddings with high-resolution representations. Second, slide-level knowledge distillation trains a low-resolution student MIL model under both slide-level supervision and teacher guidance. At inference time, LRMIL operates exclusively on low-resolution patches, substantially reducing data preprocessing and computational cost. Extensive experiments on multiple WSI benchmarks demonstrate that LRMIL consistently outperforms state-of-the-art MIL methods while achieving more efficient inference. These results highlight LRMIL as a practical and scalable solution for WSI analysis in clinical pathology.