The aggressiveness of prostate cancer is primarily assessed from histopathological data using the Gleason scoring system. Conventional artificial intelligence (AI) approaches can predict Gleason scores, but often lack explainability, which may limit clinical acceptance. Here, we present an alternative, inherently explainable AI that circumvents the need for post-hoc explainability methods. The model was trained on 1,015 tissue microarray core images, annotated with detailed pattern descriptions by 54 international pathologists following standardized guidelines. It uses pathologist-defined terminology and was trained using soft labels to capture data uncertainty. This approach enables robust Gleason pattern segmentation despite high interobserver variability. The model achieved comparable or superior performance to direct Gleason pattern segmentation (Dice score: 0.713 ± 0.003 vs. 0.691 ± 0.010 ) while providing interpretable outputs. We release this dataset to encourage further research on segmentation in medical tasks with high subjectivity and to deepen insights into pathologists' reasoning.
Nature communications. 2025 Oct 08*** epublish ***
Gesa Mittmann, Sara Laiouar-Pedari, Hendrik A Mehrtens, Sarah Haggenmüller, Tabea-Clara Bucher, Tirtha Chanda, Nadine T Gaisa, Mathias Wagner, Gilbert Georg Klamminger, Tilman T Rau, Christina Neppl, Eva Maria Compérat, Andreas Gocht, Monika Haemmerle, Niels J Rupp, Jula Westhoff, Irene Krücken, Maximilian Seidl, Christian M Schürch, Marcus Bauer, Wiebke Solass, Yu Chun Tam, Florian Weber, Rainer Grobholz, Jaroslaw Augustyniak, Thomas Kalinski, Christian Hörner, Kirsten D Mertz, Constanze Döring, Andreas Erbersdobler, Gabriele Deubler, Felix Bremmer, Ulrich Sommer, Michael Brodhun, Jon Griffin, Maria Sarah L Lenon, Kiril Trpkov, Liang Cheng, Fei Chen, Angelique Levi, Guoping Cai, Tri Q Nguyen, Ali Amin, Alessia Cimadamore, Ahmed Shabaik, Varsha Manucha, Nazeel Ahmad, Nidia Messias, Francesca Sanguedolce, Diana Taheri, Ezra Baraban, Liwei Jia, Rajal B Shah, Farshid Siadat, Nicole Swarbrick, Kyung Park, Oudai Hassan, Siamak Sakhaie, Michelle R Downes, Hiroshi Miyamoto, Sean R Williamson, Tim Holland-Letz, Christoph Wies, Carolin V Schneider, Jakob Nikolas Kather, Yuri Tolkach, Titus J Brinker
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany., Institute of Pathology, RWTH Aachen University, Aachen, Germany., Department of Pathology, University of Saarland, Homburg Saar Campus, Homburg Saar, Germany., Heinrich-Heine-University and University Hospital Düsseldorf, Düsseldorf, Germany., Department of Pathology, Medical University of Vienna, Vienna, Austria., Institute of Pathology, University Hospital Schleswig-Holstein, Lübeck, Germany., Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany., Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland., Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany., Institute of Pathology, Klinikum Bremen Mitte, Bremen, Germany., Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany., Institute of Tissue Medicine and Pathology, University Bern, Bern, Switzerland., Institute of Pathology, Georgius Agricola Foundation Ruhr, Ruhr University Bochum, Bochum, Germany., Institute of Pathology, University of Regensburg, Regensburg, Germany., Faculty of Medicine, University of Zurich, Zurich, Switzerland., Laborteam Pathology, Goldach, Switzerland., Institute of Pathology, Brandenburg Medical School Theodor Fontane, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany., Institute for Pathology, University Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland., Pathology Zwickau, MVZ diagnosticum Stollberg, Zweigpraxis Zwickau, Zwickau, Germany., Institute of Pathology, University Medicine Rostock, Rostock, Germany., Institute of Pathology, Kreiskliniken Reutlingen, Reutlingen, Germany., Institute of Pathology, University Medical Center Goettingen, Goettingen, Germany., Institute of Pathology, University Hospital of Dresden, Dresden, Germany., Institute of Pathology and Neuropathology, HELIOS Klinikum Erfurt, Erfurt, Germany., School of Medicine and Population Health, University of Sheffield, Sheffield, UK., Department of Pathology, University of Santo Tomas Hospital, Manila, Philippines., Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, Calgary, AB, Canada., Department of Pathology and Laboratory Medicine, Department of Surgery (Urology), Brown University Warren Alpert Medical School, the Legorreta Cancer Center at Brown University, and Brown University Health, Providence, RI, USA., Department of Pathology, NYU Langone Health, New York, NY, USA., Department of Pathology, Yale University School of Medicine, New Haven, CT, USA., Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands., Department of Pathology, Warren Alpert Medical School of Brown University, Providence, RI, USA., Pathological Anatomy, University of Udine, Udine, Friuli-Venezia Giulia, Italy., Department of Pathology, UC San Diego School of Medicine, La Jolla, CA, USA., Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA., University of South Florida, Morsani College of Medicine, Department of Pathology & Cell Biology and James A. Haley Veterans' Hospital, Tampa, FL, USA., Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA., Department of Pathology, University of Foggia, Foggia, Italy., Isfahan Kidney Diseases Research Center, Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran., Department of Pathology, Johns Hopkins University, Baltimore, MD, USA., Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia., Department of Pathology, Henry Ford Health System, Detroit, MI, USA., Department of Anatomical Pathology, Frankston Laboratory, Dorevitch Pathology, Frankston, VIC, Australia., Anatomic Pathology, Precision Diagnostics & Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada., Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA., Department of Pathology, Diagnostics Institute, Cleveland Clinic, Cleveland, OH, USA., Division of Biostatistics, German Cancer Research Center(DKFZ), Heidelberg, Germany., Department of Internal Medicine, University Hospital Aachen, RWTH University of Aachen, Aachen, Germany., Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany., Institute of Pathology, University Hospital Cologne, Cologne, Germany., Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany. .