Representation-Centric Deep Learning for Multi-Class, Multi-Organ Histopathology Image Classification

Imaging-based multi-omics derived from digital histopathology provides a valuable approach for characterizing tumor heterogeneity from routine clinical specimens. However, robust multi-cancer histopathological analysis remains challenging due to pronounced intra-tumor variability, inter-organ morphological overlap, and sensitivity to staining and acquisition variations, which can limit the generalizability of deep learning models. These limitations are largely driven by insufficient representation learning, particularly in multi-organ and multi-class diagnostic settings. In this study, we propose a hierarchically regularized representation learning framework for multi-cancer histopathological image analysis that models imaging-based features across multiple organs and diagnostic categories. The framework integrates complementary mechanisms to capture fine-grained cellular morphology, long-range tissue architecture, and organ-aware diagnostic semantics within a unified computational model. A hierarchical supervision strategy guides the network to reduce entanglement between organ-level structural characteristics and disease-specific diagnostic patterns in the learned representations. The method operates without pixel-level annotations or handcrafted morphological priors, supporting scalable experimental evaluation. We demonstrate the approach on balanced lung and colon cancer histopathology cohorts, achieving 96.5% accuracy on lung cancer classification and 96.8% accuracy on colon cancer classification. Ablation and robustness analyses further validate the contributions of hierarchical regularization and consistency learning. Overall, this work provides a demonstrated proof-of-concept framework for representation-centric imaging-based analysis in multi-organ histopathology under the evaluated dataset conditions.