Synergizing Deep Learning and Biological Heuristics for Extreme Long-Tail White Blood Cell Classification

Abstract: Automated white blood cell (WBC) classification is essential for leukemia screening but remains challenged by extreme class imbalance, long-tail distributions, and domain shift, leading deep models to overfit dominant classes and fail on rare subtypes. We propose a hybrid framework for rare-class generalization that integrates a generative Pix2Pix-based restoration module for artifact removal, a Swin Transformer ensemble with MedSigLIP contrastive embeddings for robust representation learning, and a biologically-inspired refinement step using geometric spikiness and Mahalanobis-based morphological constraints to recover out-of-distribution predictions. Evaluated on the WBCBench 2026 challenge, our method achieves a Macro-F1 of 0.77139 on the private leaderboard, demonstrating strong performance under severe imbalance and highlighting the value of incorporating biological priors into deep learning for hematological image analysis.