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Exploiting Low-Dimensional Manifold of Features for Few-Shot Whole Slide Image Classification

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Few-shot Whole Slide Image (WSI) classification is severely hampered by overfitting. We argue that this is not merely a data-scarcity issue but a fundamentally geometric problem. Grounded in the manifold hypothesis, our analysis shows that features from pathology foundation models exhibit a low-dimensional manifold geometry that is easily perturbed by downstream models. This insight reveals a key potential issue in downstream multiple instance learning models: linear layers are geometry-agnostic and, as we show empirically, can distort the manifold geometry of the features. To address this, we propose the Manifold Residual (MR) block, a plug-and-play module that is explicitly geometry-aware. The MR block reframes the linear layer as residual learning and decouples it into two pathways: (1) a fixed, random matrix serving as a geometric anchor that approximately preserves topology while also acting as a spectral shaper to sharpen the feature spectrum; and (2) a trainable, low-rank residual pathway that acts as a residual learner for task-specific adaptation, with its structural bottleneck explicitly mirroring the low effective rank of the features. This decoupling imposes a structured inductive bias and reduces learning to a simpler residual fitting task. Through extensive experiments, we demonstrate that our approach achieves state-of-the-art results with significantly fewer parameters, offering a new paradigm for few-shot WSI classification. Code is available in https://github.com/BearCleverProud/MR-Block.

Conghao Xiong, Zhengrui Guo, Zhe Xu, Yifei Zhang, Raymond Kai-Yu Tong, Si Yong Yeo, Hao Chen, Joseph J. Y. Sung, Irwin King• 2025

Related benchmarks

TaskDatasetResultRank
Whole Slide Image classificationCAMELYON16 (test)
AUC0.9371
163
Slide-level classificationTCGA NSCLC (test)
Accuracy89.11
96
Whole Slide Image classificationTCGA-RCC (test)
AUC98.6
90
ClassificationCAMELYON16 (test)--
69
WSI ClassificationNSCLC
Accuracy89.1
53
Multiple Instance Learning ClassificationCamelyon16
AUC93.7
44
Multiple Instance Learning ClassificationRCC
AUC0.986
44
ClassificationNSCLC (test)
AUPRC96.3
16
ClassificationRCC (test)
AUPRC97.2
16
Treatment Response PredictionBoehmk
AUC65.4
6
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