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.

Teacher-Student Model for Detecting and Classifying Mitosis in the MIDOG 2025 Challenge

Counting mitotic figures is time-intensive for pathologists and leads to inter-observer variability. Artificial intelligence (AI) promises a solution by automatically detecting mitotic figures while maintaining decision consistency. However, AI tools are susceptible to domain shift, where a significant drop in performance can occur due to differences in the training and testing sets, including morphological diversity between organs, species, and variations in staining protocols. Furthermore, the number of mitoses is much less than the count of normal nuclei, which introduces severely imbalanced data for the detection task. In this work, we formulate mitosis detection as a pixel-level segmentation and propose a teacher-student model that simultaneously addresses mitosis detection (Track 1) and atypical mitosis classification (Track 2). Our method is based on a UNet segmentation backbone that integrates domain generalization modules, namely contrastive representation learning and domain-adversarial training. A teacher-student strategy is employed to generate pixel-level pseudo-masks not only for annotated mitoses and hard negatives but also for normal nuclei, thereby enhancing feature discrimination and improving robustness against domain shift. For the classification task, we introduce a multi-scale CNN classifier that leverages feature maps from the segmentation model within a multi-task learning paradigm. On the preliminary test set, the algorithm achieved an F1 score of 0.7660 in Track 1 and balanced accuracy of 0.8414 in Track 2, demonstrating the effectiveness of integrating segmentation-based detection and classification into a unified framework for robust mitosis analysis.

MLP-SRGAN: A Single-Dimension Super Resolution GAN using MLP-Mixer

We propose a novel architecture called MLP-SRGAN, which is a single-dimension Super Resolution Generative Adversarial Network (SRGAN) that utilizes Multi-Layer Perceptron Mixers (MLP-Mixers) along with convolutional layers to upsample in the slice direction. MLP-SRGAN is trained and validated using high resolution (HR) FLAIR MRI from the MSSEG2 challenge dataset. The method was applied to three multicentre FLAIR datasets (CAIN, ADNI, CCNA) of images with low spatial resolution in the slice dimension to examine performance on held-out (unseen) clinical data. Upsampled results are compared to several state-of-the-art SR networks. For images with high resolution (HR) ground truths, peak-signal-to-noise-ratio (PSNR) and structural similarity index (SSIM) are used to measure upsampling performance. Several new structural, no-reference image quality metrics were proposed to quantify sharpness (edge strength), noise (entropy), and blurriness (low frequency information) in the absence of ground truths. Results show MLP-SRGAN results in sharper edges, less blurring, preserves more texture and fine-anatomical detail, with fewer parameters, faster training/evaluation time, and smaller model size than existing methods. Code for MLP-SRGAN training and inference, data generators, models and no-reference image quality metrics will be available at https://github.com/IAMLAB-Ryerson/MLP-SRGAN.