MorphoNet: Morphological sub-region-based structure learning for WSI analysis

Representation learning of Whole slide image (WSI) is fundamental to computational pathology, enabling tasks such as tumor subtyping, survival prediction, and cancer grading. Existing methods typically tile WSIs into thousands of small patches and aggregate patch features into slide-level embeddings, but this patch-centric paradigm suffers from redundancy and suboptimal spatial modeling. Built upon these patch-level embeddings, Multiple Instance Learning (MIL) methods overfit to scattered discriminative patches, graph-based models mainly capture local neighborhoods, and prototype-based approaches often ignore spatial coherence and under-represent rare tissue patterns. To address these challenges, we propose MorphoNet, a Morphological structure learning Network that captures long-range spatial tissue relationships while extracting informative morphological patterns. The key idea of MorphoNet is Morphological Sub-Region Grouping (MSRG), which clusters spatially adjacent patches with similar appearance into compact sub-region embeddings, reducing redundancy and forming semantically coherent morphological units. Sub-region graph is then constructed and processed by a lightweight Graph Neural Network (GNN) to model contextual dependencies and derive slide-level representations. Importantly, MSRG is a plug-and-play module that can be integrated into MIL, graph-based, and prototype-based pipelines, consistently improving their performance. Experiments on ten public benchmarks demonstrate that MorphoNet achieves superior performance on tumor subtyping and survival prediction. Our code is available at https://github.com/fuying-wang/MorphoNet.