Mitosis Detection in the Wild: Multi-Tumor and Context-Aware Generalization in the MIDOG 2025 Challenge

Automated mitosis detection is a well-established task in computational pathology. While previous benchmarks focused on scanner-induced domain shift, clinical "real-world" application requires models to be robust across the vast variance to be expected in the histological landscape. The MItosis DOmain Generalization (MIDOG) 2025 challenge was designed to evaluate algorithmic performance across unprecedented biological and contextual diversity. We curated a test dataset of 365 cases, encompassing 12 distinct human, canine and feline tumor types, digitized across multiple scanning platforms. Moving beyond hand-selected hotspots, the challenge required detection also in random tissue areas (representative of the whole slide detection situation) and challenging areas (areas rich in hard negatives). In the second track, we introduced the classification of atypical mitotic figures (AMFs). There were 18 teams submitting to the detection track, with F1 scores ranging up to 0.740. In the AMF detection track, we had 21 submissions with balanced accuracy values up to 0.908. Our analysis reveals that while most models perform reliably in traditional hotspots, significant performance degradation occurs in challenging ROIs, where false positive rates tripled. Furthermore, performance varied significantly across the 12 tumor types, highlighting "blind spots" in current state-of-the-art architectures when encountering rare or highly pleomorphic malignancies. Moreover, we evaluated the effectiveness of ensembling and found a mean increases of 1.5 and 1.3 percentage points in F1 score and balanced accuracy, respectively. In contrast, TTA showed no relevant improvement. MIDOG 2025 demonstrates that "in the wild" mitosis detection remains a significant hurdle. The transition from hotspot-only evaluation to a multi-contextual framework provides a more realistic proxy for clinical reliability.

Mix, Align, Distil: Reliable Cross-Domain Atypical Mitosis Classification

Atypical mitotic figures (AMFs) are important histopathological markers yet remain challenging to identify consistently, particularly under domain shift stemming from scanner, stain, and acquisition differences. We present a simple training-time recipe for domain-robust AMF classification in MIDOG 2025 Task 2. The approach (i) increases feature diversity via style perturbations inserted at early and mid backbone stages, (ii) aligns attention-refined features across sites using weak domain labels (Scanner, Origin, Species, Tumor) through an auxiliary alignment loss, and (iii) stabilizes predictions by distilling from an exponential moving average (EMA) teacher with temperature-scaled KL divergence. On the organizer-run preliminary leaderboard for atypical mitosis classification, our submission attains balanced accuracy of 0.8762, sensitivity of 0.8873, specificity of 0.8651, and ROC AUC of 0.9499. The method incurs negligible inference-time overhead, relies only on coarse domain metadata, and delivers strong, balanced performance, positioning it as a competitive submission for the MIDOG 2025 challenge.