Multi-Stage Fine-Tuning of Pathology Foundation Models with Head-Diverse Ensembling for White Blood Cell Classification

Abstract

The classification of white blood cells (WBCs) from peripheral blood smears is critical for the diagnosis of leukemia. However, automated approaches still struggle due to challenges including class imbalance, domain shift, and morphological continuum confusion, where adjacent maturation stages exhibit subtle, overlapping features. We present a multi-stage fine-tuning methodology for 13-class WBC classification in the WBCBench 2026 Challenge (ISBI 2026). Our best-performing model is a fine-tuned DINOBloom-base, on which we train multiple classifier head families (linear, cosine, and multilayer perceptron (MLP)). The cosine head performed best on the mature granulocyte boundary (Band neutrophil (BNE) F1 = 0.470), the linear head on more immature granulocyte classes (Metamyelocyte (MMY) F1 = 0.585), and the MLP head on the most immature granulocyte (Promyelocyte (PMY) F1 = 0.733), revealing class-specific specialization. Based on this specialization, we construct a head-diverse ensemble, where the MLP head acts as the primary predictor, and its predictions within the four predefined confusion pairs are replaced only when two other head families agree. We further show that cases consistently misclassified by all models are substantially enriched for probable labeling errors or inherent morphological ambiguity.