: Histopathological grading remains the cornerstone of risk stratification in prostate cancer, yet conventional Gleason-based assessment is limited by interobserver variability and by the biological heterogeneity concealed within Gleason pattern 4. This review examines the evolution of prostate cancer grading from the original Gleason system to contemporary Grade Groups and to newer morphology-based frameworks that seek to refine prognostic stratification. Particular attention is given to the distinction between patterns 3 and 4, which remains clinically pivotal but diagnostically challenging, especially in the setting of poorly formed glands. By contrast, cribriform architecture has emerged as one of the most reproducible and prognostically adverse components of pattern 4. Intraductal carcinoma of the prostate (IDC-P), which often overlaps morphologically and biologically with cribriform carcinoma, is similarly associated with aggressive disease and is now addressed within a more unified diagnostic and grading framework following the recent joint GUPS/ISUP recommendations. Outcome-based morphometric studies further suggest that a diameter threshold of approximately 0.25 mm can identify large cribriform glands with particularly adverse behavior, although standardization remains incomplete. These observations have contributed to the development of a risk-oriented taxonomy in which adverse architectural features may carry greater prognostic weight than numerical grade alone. Finally, we discuss how digital pathology and artificial intelligence are extending this conceptual shift by improving diagnostic reproducibility, enabling quantitative detection of cribriform morphology and supporting outcome-oriented histology-based risk prediction. Together, these developments suggest that prostate cancer grading is moving from a purely descriptive system toward a more integrated and biologically informed model of risk assessment.
The evolution of prostate cancer grading: from Gleason score to risk taxonomy and the artificial intelligence revolution
Munari, Enrico
;Antonini, Pietro;Cima, Luca;Polati, Rita;Caliò, Anna;Gobbo, Stefano Tinazzi Martini;Antonelli, Alessandro;Bertolo, Riccardo G;Brunelli, Matteo
2026-01-01
Abstract
: Histopathological grading remains the cornerstone of risk stratification in prostate cancer, yet conventional Gleason-based assessment is limited by interobserver variability and by the biological heterogeneity concealed within Gleason pattern 4. This review examines the evolution of prostate cancer grading from the original Gleason system to contemporary Grade Groups and to newer morphology-based frameworks that seek to refine prognostic stratification. Particular attention is given to the distinction between patterns 3 and 4, which remains clinically pivotal but diagnostically challenging, especially in the setting of poorly formed glands. By contrast, cribriform architecture has emerged as one of the most reproducible and prognostically adverse components of pattern 4. Intraductal carcinoma of the prostate (IDC-P), which often overlaps morphologically and biologically with cribriform carcinoma, is similarly associated with aggressive disease and is now addressed within a more unified diagnostic and grading framework following the recent joint GUPS/ISUP recommendations. Outcome-based morphometric studies further suggest that a diameter threshold of approximately 0.25 mm can identify large cribriform glands with particularly adverse behavior, although standardization remains incomplete. These observations have contributed to the development of a risk-oriented taxonomy in which adverse architectural features may carry greater prognostic weight than numerical grade alone. Finally, we discuss how digital pathology and artificial intelligence are extending this conceptual shift by improving diagnostic reproducibility, enabling quantitative detection of cribriform morphology and supporting outcome-oriented histology-based risk prediction. Together, these developments suggest that prostate cancer grading is moving from a purely descriptive system toward a more integrated and biologically informed model of risk assessment.
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