Old School, New Insight: Histomorphology in the Modern Biomarker Era of Risk Stratification of Prostate Cancer

How to cite: Nguyen, Jane K. “Old School, New Insight: Histomorphology in the Modern Biomarker Era of Risk Stratification of Prostate Cancer.” September 15, 2025. Accessed Oct 2026. https://grandroundsinurology.com/old-school-new-insight-histomorphology-in-the-modern-biomarker-era-of-risk-stratification-of-prostate-cancer/

Summary

Jane K. Nguyen, MD, PhD, Director of Genitourinary Pathology, Cleveland Clinic, Cleveland, Ohio, reviews the role of histomorphology in prostate cancer in the context of modern biomarkers. She emphasizes that while genomic classifiers, artificial intelligence platforms, and advanced imaging have transformed diagnostics, histologic architecture remains universally available, cost effective, and strongly prognostic.

Dr. Nguyen outlines the evolution of grading systems from the original Gleason score to the grade group system, highlighting refinements that improved prognostic accuracy. Particular attention is given to cribriform growth and intraductal carcinoma, which are associated with adverse outcomes including biochemical recurrence, metastasis, and disease specific mortality. Large cribriform glands exceeding 0.25 millimeters in diameter are especially high risk. She introduces the unfavorable histology classifier, incorporating large cribriform, intraductal, and other adverse morphologies. Within grade group three cancers, the classifier distinguishes patients with substantially different outcomes.

Dr. Nguyen also discusses reproducibility challenges. Even among experienced genitourinary pathologists, agreement on intermediate patterns such as Gleason 3+4 versus 4+3 can be limited. She notes that consensus guidelines have improved reporting consistency; however, variability remains, particularly in the incorporation of intraductal carcinoma. She further notes that recent studies have shown that classifying biopsies as having favorable or unfavorable histology achieves high interobserver agreement and provides meaningful clinical guidance.

Dr. Nguyen argues that histologic architecture remains a dynamic and essential biomarker and that integration of histomorphology with molecular classifiers and artificial intelligence will enable more accurate and individualized risk stratification.

The Global Summit on Precision Diagnosis and Treatment of Prostate Cancer is a unique multi-disciplinary forum organized to inform the key health care stakeholders about the emerging advances in clinical case and research and create a consensus-based vision for the future of precision care and educational and research strategy for its realization. The mission of the Summit is to fill the currently existing gap between the key experts of in vivo imaging, the world authorities in the in vitro fluid- and tissue-based molecular diagnostics, including genomics, and thought leaders in the development of novel observation strategies (e.g., active surveillance, or AS) and therapeutic interventions.