Pathologist-like explainable AI for interpretable Gleason grading in prostate cancer
Nature Communications, vol. 16, pp. 8959
Abstract
Abstract 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: $${0.713}_{\pm 0.003}$$ 0.713 ± 0.003 vs. $${0.691}_{\pm 0.010}$$ 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.
Authors 66
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German Cancer Research Center · Heidelberg University
Affiliation as printed
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany
Medical Faculty, Heidelberg University, Heidelberg, Germany
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Affiliation as printed
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Affiliation as printed
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Affiliation as printed
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Affiliation as printed
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University
Affiliation as printed
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany
Medical Faculty, Heidelberg University, Heidelberg, Germany
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Universität Ulm · University Hospital Ulm · RWTH Aachen University
Affiliation as printed
Institute of Pathology, RWTH Aachen University, Aachen, Germany
Institute of Pathology, University Hospital, University of Ulm, Ulm, Germany
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Affiliation as printed
Department of Pathology, University of Saarland, Homburg Saar Campus, Homburg Saar, Germany
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Heinrich-Heine-University and University Hospital Düsseldorf, Düsseldorf, Germany
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Heinrich-Heine-University and University Hospital Düsseldorf, Düsseldorf, Germany
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Affiliation as printed
Department of Pathology, Medical University of Vienna, Vienna, Austria
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University Hospital Schleswig-Holstein · University of Lübeck
Affiliation as printed
Institute of Pathology, University Hospital Schleswig-Holstein, Lübeck, Germany
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Martin Luther University Halle-Wittenberg
Affiliation as printed
Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
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University of Zurich · University Hospital Zurich
Affiliation as printed
Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
Faculty of Medicine, University of Zurich, Zurich, Switzerland
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Städtisches Klinikum Karlsruhe
Affiliation as printed
Institute of Pathology, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany
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Affiliation as printed
Institute of Pathology, Klinikum Bremen Mitte, Bremen, Germany
PathoNext GmbH, Leipzig, Germany
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Düsseldorf University Hospital · Heinrich Heine University Düsseldorf
Affiliation as printed
Heinrich-Heine-University and University Hospital Düsseldorf, Düsseldorf, Germany
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Universitätsklinikum Tübingen · University of Tübingen
Affiliation as printed
Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany
Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany
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Martin Luther University Halle-Wittenberg
Affiliation as printed
Institute of Pathology, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany
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Institute of Tissue Medicine and Pathology, University Bern, Bern, Switzerland
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Institute of Pathology, Georgius Agricola Foundation Ruhr, Ruhr University Bochum, Bochum, Germany
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Institute of Pathology, University of Regensburg, Regensburg, Germany
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University of Zurich · Kantonsspital Aarau
Affiliation as printed
Faculty of Medicine, University of Zurich, Zurich, Switzerland
Institute of Pathology, Cantonal Hospital Aarau, Aarau, Switzerland
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Affiliation as printed
Laborteam Pathology, Goldach, Switzerland
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Medizinische Hochschule Brandenburg Theodor Fontane · Universitätsklinikum Brandenburg an der Havel
Affiliation as printed
Institute of Pathology, Brandenburg Medical School Theodor Fontane, University Hospital Brandenburg an der Havel, Brandenburg an der Havel, Germany
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Heidelberg University · Medizinische Fakultät Mannheim
Affiliation as printed
Institute for Pathology, University Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
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University of Basel · University Hospital of Basel
Affiliation as printed
Department of Biomedicine (DBM), Pathology of Infectious and Immunologic Diseases, University of Basel, Basel, Switzerland
Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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Affiliation as printed
Pathology Zwickau, MVZ diagnosticum Stollberg, Zweigpraxis Zwickau, Zwickau, Germany
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Institute of Pathology, University Medicine Rostock, Rostock, Germany
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Institute of Pathology, Kreiskliniken Reutlingen, Reutlingen, Germany
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Institute of Pathology, University Medical Center Goettingen, Goettingen, Germany
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Institute of Pathology, University Hospital of Dresden, Dresden, Germany
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Institute of Pathology and Neuropathology, HELIOS Klinikum Erfurt, Erfurt, Germany
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School of Medicine and Population Health, University of Sheffield, Sheffield, UK
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University of Santo Tomas Hospital · National Kidney and Transplant Institute
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Department of Pathology and Laboratory Medicine, National Kidney and Transplant Institute, Quezon City, Philippines
Department of Pathology, University of Santo Tomas Hospital, Manila, Philippines
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University of Calgary · Rockyview General Hospital
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Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, Calgary, AB, Canada
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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
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Department of Pathology, NYU Langone Health, New York, NY, USA
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Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
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Department of Pathology, Yale University School of Medicine, New Haven, CT, USA
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University Medical Center Utrecht
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Department of Pathology, University Medical Centre Utrecht, Utrecht, The Netherlands
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Department of Pathology, Warren Alpert Medical School of Brown University, Providence, RI, USA
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Affiliation as printed
Pathological Anatomy, University of Udine, Udine, Friuli-Venezia Giulia, Italy
Pathological Anatomy, University of Udine, Udine, Friuli-Venezia Giulia, Italy
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University of California San Diego
Affiliation as printed
Department of Pathology, UC San Diego School of Medicine, La Jolla, CA, USA
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University of Mississippi Medical Center
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Department of Pathology, University of Mississippi Medical Center, Jackson, MS, USA
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University of South Florida · James A. Haley Veterans' Hospital
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University of South Florida, Morsani College of Medicine, Department of Pathology & Cell Biology and James A. Haley Veterans' Hospital, Tampa, FL, USA
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Washington University in St. Louis
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Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA
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Department of Pathology, University of Foggia, Foggia, Italy
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Isfahan University of Medical Sciences · Tehran University of Medical Sciences
Affiliation as printed
Isfahan Kidney Diseases Research Center, Department of Pathology, Isfahan University of Medical Sciences, Isfahan, Iran
Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
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The University of Texas Southwestern Medical Center
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Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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The University of Texas Southwestern Medical Center
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Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA
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University of Calgary · Rockyview General Hospital
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Department of Pathology and Laboratory Medicine, Cumming School of Medicine, University of Calgary, Rockyview General Hospital, Calgary, AB, Canada
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The University of Western Australia · Pathwest Laboratory Medicine
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Department of Anatomical Pathology, PathWest Laboratory Medicine WA, Perth, WA, Australia
Division of Pathology and Laboratory Medicine, UWA Medical School, Crawley, WA, Australia
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Department of Pathology, NYU Langone Health, New York, NY, USA
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Department of Pathology, Henry Ford Health System, Detroit, MI, USA
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Department of Anatomical Pathology, Frankston Laboratory, Dorevitch Pathology, Frankston, VIC, Australia
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Sunnybrook Health Science Centre
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Anatomic Pathology, Precision Diagnostics & Therapeutics Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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University of Rochester Medicine · University of Rochester
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Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA
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Department of Pathology, Diagnostics Institute, Cleveland Clinic, Cleveland, OH, USA
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Affiliation as printed
Division of Biostatistics, German Cancer Research Center(DKFZ), Heidelberg, Germany
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German Cancer Research Center · Heidelberg University
Affiliation as printed
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany
Medical Faculty, Heidelberg University, Heidelberg, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Department of Internal Medicine, University Hospital Aachen, RWTH University of Aachen, Aachen, Germany
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University of Leeds · University Hospital Heidelberg · National Center for Tumor Diseases · University Hospital Carl Gustav Carus · Else Kröner Fresenius Center for Digital Health · Technische Universität Dresden
Affiliation as printed
Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany
Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, Germany
Pathology & Data Analytics, Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK
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University of Cologne · University Hospital Cologne
Affiliation as printed
Institute of Pathology, University Hospital Cologne, Cologne, Germany
Medical Faculty, University of Cologne, Cologne, Germany
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Titus Josef Brinker corresponding
Affiliation as printed
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany. titus.brinker@dkfz.de
Division of Digital Prevention, Diagnostics and Therapy Guidance, German Cancer Research Center (DKFZ), Heidelberg, Germany
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