Genomics and Histopathology in Interstitial Cystitis/Bladder Pain Syndrome.

Aims: In April of 2025, a Global Consensus meeting on IC/BPS was held in Winston-Salem, NC. The goal of this meeting was to establish global consensus in diagnostic criteria, phenotyping, treatment outcome assessment, and possible etiopathology in interstitial cystitis/bladder pain syndrome (IC/BPS). Our sub-committee focused on developing a consensus document on histopathology in IC/BPS.

Methods: Narrative review.

Results: Herein we discuss histological and molecular distinctions of Hunner lesion disease (HLD) and non-Hunner lesion disease (non-HLD) in IC/BPS, including urothelial alterations, inflammatory changes, vascularization and fibrosis, and neurophysiological dysfunction. The molecular and histological characteristics of HLD make it distinct from non-HLD. HLD is histologically characterized by urothelial denudation and subepithelial chronic inflammation featured by B-cell dominant lymphoplasmacytic infiltration, while non-HLD shows subtle inflammatory changes with preserved urothelial layers. Some cases of non-HLD reflect a component of multi-systemic pain syndrome driven by altered neurophysiological networks within the central or peripheral nervous system.

Conclusions: Molecular and histological characteristics revealed that HLD and non-HLD are distinct disease entities as the former is an inflammatory disease of the urinary bladder and the latter may be represented by systemic neurophysiological disorder, rather than pathology that is limited to the bladder. This concept could be useful in phenotyping, diagnosis, and development of biomarkers for IC/BPS.

Trial Registration: No new data were generated for this manuscript; no clinical trial was conducted.