Bruno Märkl

Dominik Müller, Philip Meyer, Lukas Rentschler et al.

Advances in digital pathology and artificial intelligence (AI) offer promising opportunities for clinical decision support and enhancing diagnostic workflows. Previous studies already demonstrated AI's potential for automated Gleason grading, but lack state-of-the-art methodology and model reusability. To address this issue, we propose DeepGleason: an open-source deep neural network based image classification system for automated Gleason grading using whole-slide histopathology images from prostate tissue sections. Implemented with the standardized AUCMEDI framework, our tool employs a tile-wise classification approach utilizing fine-tuned image preprocessing techniques in combination with a ConvNeXt architecture which was compared to various state-of-the-art architectures. The neural network model was trained and validated on an in-house dataset of 34,264 annotated tiles from 369 prostate carcinoma slides. We demonstrated that DeepGleason is capable of highly accurate and reliable Gleason grading with a macro-averaged F1-score of 0.806, AUC of 0.991, and Accuracy of 0.974. The internal architecture comparison revealed that the ConvNeXt model was superior performance-wise on our dataset to established and other modern architectures like transformers. Furthermore, we were able to outperform the current state-of-the-art in tile-wise fine-classification with a sensitivity and specificity of 0.94 and 0.98 for benign vs malignant detection as well as of 0.91 and 0.75 for Gleason 3 vs Gleason 4 & 5 classification, respectively. Our tool contributes to the wider adoption of AI-based Gleason grading within the research community and paves the way for broader clinical application of deep learning models in digital pathology. DeepGleason is open-source and publicly available for research application in the following Git repository: https://github.com/frankkramer-lab/DeepGleason.

Dominik Müller, Philip Meyer, Lukas Rentschler et al.

Prostate cancer is a dominant health concern calling for advanced diagnostic tools. Utilizing digital pathology and artificial intelligence, this study explores the potential of 11 deep neural network architectures for automated Gleason grading in prostate carcinoma focusing on comparing traditional and recent architectures. A standardized image classification pipeline, based on the AUCMEDI framework, facilitated robust evaluation using an in-house dataset consisting of 34,264 annotated tissue tiles. The results indicated varying sensitivity across architectures, with ConvNeXt demonstrating the strongest performance. Notably, newer architectures achieved superior performance, even though with challenges in differentiating closely related Gleason grades. The ConvNeXt model was capable of learning a balance between complexity and generalizability. Overall, this study lays the groundwork for enhanced Gleason grading systems, potentially improving diagnostic efficiency for prostate cancer.

Marco Gustav, Fabian Wolf, Christina Glasner et al.

The rapid adoption of transformer-based models in computational pathology has enabled prediction of molecular and clinical biomarkers from H&E whole-slide images, yet interpretability has not kept pace with model complexity. While attribution- and generative-based methods are common, feature visualization approaches such as class visualizations (CVs) and activation atlases (AAs) have not been systematically evaluated for these models. We developed a visualization framework and assessed CVs and AAs for a transformer-based foundation model across tissue and multi-organ cancer classification tasks with increasing label granularity. Four pathologists annotated real and generated images to quantify inter-observer agreement, complemented by attribution and similarity metrics. CVs preserved recognizability for morphologically distinct tissues but showed reduced separability for overlapping cancer subclasses. In tissue classification, agreement decreased from Fleiss k = 0.75 (scans) to k = 0.31 (CVs), with similar trends in cancer subclass tasks. AAs revealed layer-dependent organization: coarse tissue-level concepts formed coherent regions, whereas finer subclasses exhibited dispersion and overlap. Agreement was moderate for tissue classification (k = 0.58), high for coarse cancer groupings (k = 0.82), and low at subclass level (k = 0.11). Atlas separability closely tracked expert agreement on real images, indicating that representational ambiguity reflects intrinsic pathological complexity. Attribution-based metrics approximated expert variability in low-complexity settings, whereas perceptual and distributional metrics showed limited alignment. Overall, concept-level feature visualization reveals structured morphological manifolds in transformer-based pathology models and provides a framework for expert-centered interrogation of learned representations across label granularities.