Robust Atypical Mitosis Classification with DenseNet121: Stain-Aware Augmentation and Hybrid Loss for Domain Generalization

Atypical mitotic figures are important biomarkers of tumor aggressiveness in histopathology, yet reliable recognition remains challenging due to severe class imbalance and variability across imaging domains. We present a DenseNet-121-based framework tailored for atypical mitosis classification in the MIDOG 2025 (Track 2) setting. Our method integrates stain-aware augmentation (Macenko), geometric and intensity transformations, and imbalance-aware learning via weighted sampling with a hybrid objective combining class-weighted binary cross-entropy and focal loss. Trained end-to-end with AdamW and evaluated across multiple independent domains, the model demonstrates strong generalization under scanner and staining shifts, achieving balanced accuracy 85.0%, AUROC 0.927, sensitivity 89.2%, and specificity 80.9% on the official test set. These results indicate that combining DenseNet-121 with stain-aware augmentation and imbalance-adaptive objectives yields a robust, domain-generalizable framework for atypical mitosis classification suitable for real-world computational pathology workflows.