Abstract
Histopathology image segmentation faces critical challenges due to the scarcity of pixel-level annotations and limited generalization across diverse tissue types and institutional settings. This paper introduces a novel self-supervised learning framework that integrates masked image modeling with contrastive learning and adaptive semantic-aware data augmentation to address these fundamental limitations. Our approach features three key innovations the first is a multi-resolution hierarchical architecture specifically designed for gigapixel whole slide images that captures both cellular-level details and tissue-level context and the second is a hybrid self-supervised learning strategy combining masked autoencoder reconstruction with multi-scale contrastive learning to learn robust feature representations without extensive annotations, and an adaptive augmentation network that preserves histological semantics while maximizing data diversity through learned transformation policies. The framework employs a progressive fine-tuning protocol with semantic-aware masking strategies and boundary-focused loss functions optimized for dense prediction tasks. Comprehensive evaluation on five diverse histopathology datasets [TCGA-BRCA, TCGA-LUAD, TCGA-COAD, CAMELYON16, and PanNuke] demonstrates substantial improvements over state-of-the-art methods, achieving a Dice coefficient of 0.825 [4.3% improvement], mIoU of 0.742 [7.8% enhancement], and significant reductions in boundary error metrics [10.7% in Hausdorff Distance, 9.5% in Average Surface Distance]. Notably, our method exhibits exceptional data efficiency, requiring only 25% of labeled data to achieve 95.6% of full performance compared to 85.2% for supervised baselines, representing a 70% reduction in annotation requirements. Cross-dataset generalization analysis reveals 13.9% improvement over existing approaches, while clinical validation by expert pathologists confirms diagnostic utility with ratings of 4.3/5.0 for clinical applicability and 4.1/5.0 for boundary accuracy. The proposed framework establishes a new paradigm for self-supervised learning in computational pathology, offering significant potential for clinical deployment where annotation resources are limited while maintaining high diagnostic accuracy across diverse institutional environments.