Pathologist-like explainable AI for interpretable Gleason grading in prostate cancer
Publication date
2025-10-08
Authors
Mittmann, Gesa
Laiouar-Pedari, Sara
Mehrtens, Hendrik A
Haggenmüller, Sarah
Bucher, Tabea-Clara
Chanda, Tirtha
Gaisa, Nadine T
Wagner, Mathias
Klamminger, Gilbert Georg
Rau, Tilman T
Editors
Advisors
Supervisors
Document Type
Article
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cc_by
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 ± 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.
Keywords
Artificial Intelligence, Humans, Male, Neoplasm Grading/methods, Observer Variation, Pathologists, Prostate/pathology, Prostatic Neoplasms/pathology, Journal Article
Citation
Mittmann, G, Laiouar-Pedari, S, Mehrtens, H A, Haggenmüller, S, Bucher, T-C, Chanda, T, Gaisa, N T, Wagner, M, Klamminger, G G, Rau, T T, Neppl, C, Compérat, E M, Gocht, A, Haemmerle, M, Rupp, N J, Westhoff, J, Krücken, I, Seidl, M, Schürch, C M, Bauer, M, Solass, W, Tam, Y C, Weber, F, Grobholz, R, Augustyniak, J, Kalinski, T, Hörner, C, Mertz, K D, Döring, C, Erbersdobler, A, Deubler, G, Bremmer, F, Sommer, U, Brodhun, M, Griffin, J, Lenon, M S L, Trpkov, K, Cheng, L, Chen, F, Levi, A, Cai, G, Nguyen, T Q, Amin, A, Cimadamore, A, Shabaik, A, Manucha, V, Ahmad, N, Messias, N, Sanguedolce, F, Taheri, D, Baraban, E, Jia, L, Shah, R B, Siadat, F, Swarbrick, N, Park, K, Hassan, O, Sakhaie, S, Downes, M R, Miyamoto, H, Williamson, S R, Holland-Letz, T, Wies, C, Schneider, C V, Kather, J N, Tolkach, Y & Brinker, T J 2025, 'Pathologist-like explainable AI for interpretable Gleason grading in prostate cancer', Nature Communications, vol. 16, no. 1, 8959. https://doi.org/10.1038/s41467-025-64712-4