Accepted for/Published in: JMIR Medical Informatics
Date Submitted: Sep 19, 2025
Open Peer Review Period: Oct 7, 2025 - Dec 2, 2025
Date Accepted: Jan 1, 2026
(closed for review but you can still tweet)
Warning: This is an author submission that is not peer-reviewed or edited. Preprints - unless they show as "accepted" - should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.
Ranking-Aware Multiple Instance Learning for Histopathology Slide Classification: Development and Validation Study
ABSTRACT
Background:
Multiple Instance Learning (MIL) is widely used for slide-level classification in digital pathology without requiring expert annotations. However, even partial expert annotations offer valuable supervision, yet few studies have effectively leveraged this information within MIL frameworks.
Objective:
This study aims to develop and evaluate a ranking-aware MIL framework, called Rank Induction, that effectively incorporates partial expert annotations to improve slide-level classification performance under realistic annotation constraints.
Methods:
We developed Rank Induction, a MIL approach that incorporates expert annotations using a pairwise rank loss inspired by RankNet. The method encourages the model to assign higher attention scores to annotated regions than to unannotated ones, guiding it to focus on diagnostically relevant patches. We evaluated Rank Induction on two public datasets and tested its robustness under three real world conditions: low-data regimes, coarse within-slide annotations, and sparse slide-level annotations.
Results:
Rank Induction outperformed existing methodologies, achieving an Area Under the Receiver Operating Characteristic curve (AUROC) of 0.840 on Camelyon16 and 0.995 on DigestPath2019. It remained robust under low-data conditions, maintaining an AUROC of 0.790 with only 60% of the training data. When using coarse annotations (with 2240-pixel padding), performance slightly declined to 0.810. Remarkably, annotating just 10% of the slides was enough to reach near-saturated performance (AUROC: 0.802 vs. 0.840 with full annotations).
Conclusions:
Incorporating expert annotations through ranking-based supervision significantly improves MIL-based classification. Rank Induction remains robust even with limited, coarse, or sparsely available annotations, demonstrating its practicality in real-world scenarios.
Citation
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