To develop and validate a pragmatic histopathological scoring system for interstitial cystitis/bladder pain syndrome (IC/BPS) that distinguishes Hunner-type interstitial cystitis (HIC) from bladder pain syndrome (BPS) and inflammatory non-HIC chronic cystitis mimicking Hunner lesions ("other cystitis").
Bladder biopsies from 96 patients were analyzed: HIC (n = 32), BPS (n = 42), and other cystitis (n = 22; bacillus Calmette-Guérin-related, follicular, and chronic bacterial cystitis). Four pathologists (A-D; A as index/model observer) independently scored hematoxylin-eosin sections using five histopathological features (inflammation, plasma cell infiltration, eosinophil infiltration, tertiary lymphoid structures, urothelial denudation; total 0-8). ROC curves were generated for HIC vs. BPS and HIC vs. other cystitis. Youden index-derived thresholds were compared across observers to select simple integer cutoffs and define an operational three-tier classification (0-2: BPS, 3-4: indeterminate, 5-8: HIC). Diagnostic performance was assessed using AUC and contingency-table metrics. Inter-observer agreement for the three-tier classification was evaluated using Fleiss' kappa.
HIC vs. BPS discrimination was excellent across pathologists (AUC 0.966-0.991; pooled AUC 0.983). HIC vs. other cystitis discrimination was moderate-to-good (AUC 0.723-0.808; pooled AUC 0.738). Overall agreement for the three-tier classification was 60.4% with Fleiss' κ = 0.657; agreement was highest for BPS and modest for other cystitis.
This hematoxylin-eosin-based scoring system enables standardized IC/BPS phenotyping, robustly separating HIC from BPS and providing a structured framework for inflammatory overlap cases, with reproducible performance across international pathologists.
World journal of urology. 2026 Jul 17*** epublish ***
Yoshiyuki Akiyama, Sachin Malde, Kostika Lako, Mai Iwaya, Takeshi Uehara, Aya Niimi, Masafumi Horie, Tetsuo Ushiku, Akiteru Goto, Haruki Kume, Yukio Homma, Mauro Cervigni, Daichi Maeda
Department of Urology, Shinshu University School of Medicine, Nagano, Japan. ., Guy's and St Thomas' NHS Foundation Trust, London, UK., Department of Medico-Surgical Sciences and Biotechnologies Histopathology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Latina, Italy., Department of Laboratory Medicine, Shinshu University School of Medicine, Nagano, Japan., Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Division of Molecular and Genomic Pathology, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan., Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan., Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan., Department of Interstitial Cystitis Medicine, Kyorin University School of Medicine, Tokyo, Japan., Department of Urology, La Sapienza University-Polo Pontino ICOT, Latina, Italy., Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. .