Viktoria Weiss

Sweta Banerjee, Timo Gosch, Sara Hester et al.

The annotation of large scale histopathology image datasets remains a major bottleneck in developing robust deep learning models for clinically relevant tasks, such as mitotic figure classification. Folder-based annotation workflows are usually slow, fatiguing, and difficult to scale. To address these challenges, we introduce SWipeable ANnotations (SWAN), an open-source, MIT-licensed web application that enables intuitive image patch classification using a swiping gesture. SWAN supports both desktop and mobile platforms, offers real-time metadata capture, and allows flexible mapping of swipe gestures to class labels. In a pilot study with four pathologists annotating 600 mitotic figure image patches, we compared SWAN against a traditional folder-sorting workflow. SWAN enabled rapid annotations with pairwise percent agreement ranging from 86.52% to 93.68% (Cohen's Kappa = 0.61-0.80), while for the folder-based method, the pairwise percent agreement ranged from 86.98% to 91.32% (Cohen's Kappa = 0.63-0.75) for the task of classifying atypical versus normal mitotic figures, demonstrating high consistency between annotators and comparable performance. Participants rated the tool as highly usable and appreciated the ability to annotate on mobile devices. These results suggest that SWAN can accelerate image annotation while maintaining annotation quality, offering a scalable and user-friendly alternative to conventional workflows.

Christof A. Bertram, Viktoria Weiss, Jonas Ammeling et al.

Supervised deep learning (DL) receives great interest for automated analysis of microscopic images with an increasing body of literature supporting its potential. The development and validation of those DL models relies heavily on the availability of high-quality, large-scale datasets. However, creating such datasets is a complex and resource-intensive process, often hindered by challenges such as time constraints, domain variability, and risks of bias in image collection and label creation. This review provides a comprehensive guide to the critical steps in dataset creation, including: 1) image acquisition, 2) selection of annotation software, and 3) annotation creation. In addition to ensuring a sufficiently large number of images, it is crucial to address sources of image variability (domain shifts) - such as those related to slide preparation and digitization - that could lead to algorithmic errors if not adequately represented in the training data. Key quality criteria for annotations are the three "C"s: correctness, completeness, and consistency. This review explores methods to enhance annotation quality through the use of advanced techniques that mitigate the limitations of single annotators. To support dataset creators, a standard operating procedure (SOP) is provided as supplemental material, outlining best practices for dataset development. Furthermore, the article underscores the importance of open datasets in driving innovation and enhancing reproducibility of DL research. By addressing the challenges and offering practical recommendations, this review aims to advance the creation of and availability to high-quality, large-scale datasets, ultimately contributing to the development of generalizable and robust DL models for pathology applications.

Sweta Banerjee, Viktoria Weiss, Taryn A. Donovan et al.

Atypical mitosis marks a deviation in the cell division process that has been shown be an independent prognostic marker for tumor malignancy. However, atypical mitosis classification remains challenging due to low prevalence, at times subtle morphological differences from normal mitotic figures, low inter-rater agreement among pathologists, and class imbalance in datasets. Building on the Atypical Mitosis dataset for Breast Cancer (AMi-Br), this study presents a comprehensive benchmark comparing deep learning approaches for automated atypical mitotic figure (AMF) classification, including end-to-end trained deep learning models, foundation models with linear probing, and foundation models fine-tuned with low-rank adaptation (LoRA). For rigorous evaluation, we further introduce two new held-out AMF datasets - AtNorM-Br, a dataset of mitotic figures from the TCGA breast cancer cohort, and AtNorM-MD, a multi-domain dataset of mitotic figures from a subset of the MIDOG++ training set. We found average balanced accuracy values of up to 0.8135, 0.7788, and 0.7723 on the in-domain AMi-Br and the out-of-domain AtNorm-Br and AtNorM-MD datasets, respectively. Our work shows that atypical mitotic figure classification, while being a challenging problem, can be effectively addressed through the use of recent advances in transfer learning and model fine-tuning techniques. We make all code and data used in this paper available in this github repository: https://github.com/DeepMicroscopy/AMi-Br_Benchmark.

Christof A. Bertram, Viktoria Weiss, Taryn A. Donovan et al.

Assessment of the density of mitotic figures (MFs) in histologic tumor sections is an important prognostic marker for many tumor types, including breast cancer. Recently, it has been reported in multiple works that the quantity of MFs with an atypical morphology (atypical MFs, AMFs) might be an independent prognostic criterion for breast cancer. AMFs are an indicator of mutations in the genes regulating the cell cycle and can lead to aberrant chromosome constitution (aneuploidy) of the tumor cells. To facilitate further research on this topic using pattern recognition, we present the first ever publicly available dataset of atypical and normal MFs (AMi-Br). For this, we utilized two of the most popular MF datasets (MIDOG 2021 and TUPAC) and subclassified all MFs using a three expert majority vote. Our final dataset consists of 3,720 MFs, split into 832 AMFs (22.4%) and 2,888 normal MFs (77.6%) across all 223 tumor cases in the combined set. We provide baseline classification experiments to investigate the consistency of the dataset, using a Monte Carlo cross-validation and different strategies to combat class imbalance. We found an averaged balanced accuracy of up to 0.806 when using a patch-level data set split, and up to 0.713 when using a patient-level split.

Marc Aubreville, Jonas Ammeling, Sweta Banerjee et al.

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.