LPD: Learnable Prototypes with Diversity Regularization for Weakly Supervised Histopathology Segmentation

Khang Le , Tuan A. Vu , Ha Thach , Ngoc Bui Lam Quang , Thanh-Huy Nguyen , Minh Hoang Le , Zhu Han , Chandra Mohan , Hien Van Nguyen ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.48550/arxiv.2512.05922

Weakly supervised semantic segmentation (WSSS) in histopathology reduces pixel-level labeling by learning from image-level labels, but it is hindered by inter-class homogeneity, intra-class heterogeneity, and CAM-induced region shrinkage (global pooling-based class activation maps whose activations highlight only the most distinctive areas and miss nearby class regions). Recent works address these challenges by constructing a clustering prototype bank and then refining masks in a separate stage; however, such two-stage pipelines are costly, sensitive to hyperparameters, and decouple prototype discovery from segmentation learning, limiting their effectiveness and efficiency. We propose a cluster-free, one-stage learnable-prototype framework with diversity regularization to enhance morphological intra-class heterogeneity coverage. Our approach achieves state-of-the-art (SOTA) performance on BCSS-WSSS, outperforming prior methods in mIoU and mDice. Qualitative segmentation maps show sharper boundaries and fewer mislabels, and activation heatmaps further reveal that, compared with clustering-based prototypes, our learnable prototypes cover more diverse and complementary regions within each class, providing consistent qualitative evidence for their effectiveness.