AI-assisted mitotic counting improves reproducibility and efficiency across multiple tumour types
Authors: Simon Graham, Mostafa Jahanifar, Quoc Dang Vu, Vygante Maskoliunaite, Donatas Petroska, Ruta Barbora Valkiuniene, Ayat Gamal Lashen, Jen Hong Ong, +10 more
Organizations: Histofy Ltd, Coventry, United Kingdom · Vilnius University Faculty of Medicine and National Center of Pathology, Affiliate of Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania · Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom · The Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom · University Hospitals Tees, Stockton-on-Tees, United Kingdom · University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom · University Hospitals of Derby and Burton NHS Foundation Trust, Derby, United Kingdom · Fundación MD Anderson Cancer Center España, Madrid, Spain
Mitotic counting is an important component of tumour grading, diagnosis and prognostic assessment across several tumour types, but manual assessment is time-consuming and subject to inter-pathologist variability. To help address these challenges, we developed MitPro, an AI tool designed to improve consistency and efficiency by directing pathologists towards regions with the highest predicted mitotic activity and highlighting mitotic figures for review, while retaining pathologist control over region selection and the final count. We evaluated its effect on the reproducibility and efficiency of mitotic counting in a retrospective, non-interventional, paired reader study comprising 385 whole-slide images from 3 centres in 3 countries and 7 tumour types using 3 different scanners. 13 pathologists participated, with each slide assessed independently by 3 pathologists without AI assistance and again with AI assistance after a minimum 2 week washout period. Across all slides, AI-assisted counting increased the intraclass correlation coefficient from 0.589 to 0.949. Mean pathologist-level median assessment time decreased from 286.4 to 127.8 seconds, corresponding to an average saving of 151.8 seconds per assessment. Improvements in agreement and efficiency were also observed in supporting analyses using HALO AP and Sectra image management systems and in 2 additional tumour types outside the main study population. AI-assisted assessment was associated with a subtle shift towards higher mitotic counts and scores, consistent with identification of more active mitotic hotspots and fewer missed mitotic figures. The frequency of score change between unassisted and AI-assisted assessment was comparable with inter-pathologist variation during routine counting. These findings support the use of MitPro as an assistive tool for more consistent and efficient mitotic assessment in routine practice.
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.
Marc Aubreville, Jonas Ammeling, Sweta Banerjee +64
Mitotic figure (MF) analysis supports tumor grading and prognostic assessment, but automated models remain sensitive to differences in tissue type and image acquisition. We present MiTHras, a task-specific pretraining framework that combines pseudo-label-guided image- and token-level contrastive learning with masked reconstruction. We construct TCGA-MF-Pseudo, a corpus of 1.8 million cell-centered images from 14 TCGA cohorts spanning 11 organ sites. Comprehensive evaluation on MF classification, detection, count-based survival prediction, and subtype classification demonstrates the efficacy of MiTHras. It achieves the highest mean F1 on all three MF classification benchmarks and both subtype benchmarks. MiTHras also outperforms general-purpose and pathology foundation encoders by a larger margin under frozen-encoder linear probing than under full fine-tuning. Although detection gains are modest due to a shared candidate-detection stage, ablations confirm that token-level supervision improves typical-versus-atypical classification and linear probing. These findings establish that MiTHras yields robust, transferable representations for automated mitotic activity assessment.
Trinh T. L. Vuong, Simon Graham, Quoc Dang Vu +5
Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, USA · Histofy Ltd, Coventry, United Kingdom · Department of Pathology, University Medical Center Ho Chi Minh City, Ho Chi Minh City, Vietnam +1
Background and Objective: Quality control is a prerequisite for whole-slide image analysis, yet the benchmarks on which quality-control methods are compared share four properties that make their reported differences hard to interpret: few independent slides, annotation concentrated in a minority of them, pooled ratio metrics with no closed-form standard error, and a single inherited train/test partition. We propose a reliability protocol for such benchmarks. Methods: The protocol quantifies four sources of variability - test-set sampling, training stochasticity, partition composition, and undocumented preprocessing - a claim is reportable only if it survives all four; three of the four cost minutes of compute. We apply it to an independent reconstruction of a published diffusion-based artifact detector, evaluated on the original 24-slide partition and against a supervised baseline. Results: The method's central mechanism reproduces: the auxiliary contrastive term improves pooled F1 from 0.673 to 0.688 and replicates under a second seed (+0.0156, p = 0.031; +0.0190, p = 0.005), although it acts on pen marking rather than the artifact types cited to motivate it. Its comparative claims do not: differences between design variants, and against the supervised baseline, fall inside the uncertainty of the evaluation. Four of 24 slides carry 70% of scored annotated pixels, giving an effective sample size of 6.2, and the inherited partition sits at the 7th percentile. An unreported tissue-restriction step excludes 41.4% of out-of-focus annotation against 2.6% of air bubble; such a gate is confounded with blur by construction. Conclusions: Small-cohort benchmarks support far weaker conclusions than current reporting implies. The four checks are cheap enough to accompany any evaluation on such a resource and separate reproducible effects from differences the evaluation cannot resolve.
Konstantinos Moutselos, Ilias Maglogiannis
Department of Digital Systems, University of Piraeus, Piraeus, Greece