Histological assessment of inflammatory infiltrates in interstitial cystitis/bladder pain syndrome (IC/BPS): a comparative study of mast cell quantification techniques [Abstract]

Introduction
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease of unknown aetiology that affects the normal pathophysiology of urinary bladder.1 Given the complex nature of pathogenesis, there are no universally accepted clinical or histological diagnostic criteria for IC/BPS. The central role of urothelial inflammation and mast cell activation in the detrusor muscle have been histologically confirmed in IC/BPS cases.2,3 However, there is no standardised diagnostic technique for evaluating, interpreting and reporting histopathological findings, such as inflammatory markers, in IC/BPS. Therefore, this retrospective study aimed to assess inflammatory cell infiltrate to better understand the role of inflammation to provide diagnostic value in histopathology reports for improved patient treatment and to compare histochemical and immunohistochemical stains for efficiency and sensitivity in detection and quantification of mast cells in detrusor muscle.

Methods
This retrospective study analysed 26 formalin-fixed paraffin-embedded bladder biopsies/tissues with confirmed IC/BPS. Inflammation was graded as acute, chronic or mix based on present inflammatory cells using Haematoxylin and Eosin staining. Eosinophils were recorded as present or absent. Mast cells were detected using three techniques: Toluidine Blue, Artisan Giemsa, and anti-CD117 immunohistochemistry. A four-point grading system (0: <5, 1: 6–10, 2: 11–20, 3: >20 mast cells/high-power field) was applied. Sensitivity was calculated based on positive mast cell detection. Lymphocyte subsets were assessed using anti-CD3 (T lymphocytes) and anti-CD20 (B lymphocytes) antibodies, and predominance was recorded in cases with moderate-to-severe inflammation.

Results
Chronic inflammation was observed in 96.2% of cases, with eosinophilic infiltration present in 76.9% (Fig 1). CD117 immunohistochemistry demonstrated the highest sensitivity for mast cell detection (73.1%) compared with Toluidine Blue (50%) and Artisan Giemsa (26.9%) (p=0.002) (Fig 2). Definite mast cell infiltration was found in 46.2% of cases, all of which were eosinophil-positive. Among these, 83.3% showed T lymphocyte predominance within the detrusor muscle. These results suggest that eosinophils and T-lymphocytes may have a synergistic role in chronic bladder inflammation.

Conclusion
This study confirmed the importance of inflammatory cell infiltrates, particularly lymphoplasmacytic, eosinophilic and mast cell components, in the histological evaluation of IC/BPS, consistent with published studies.1–5 Anti-CD117 staining was the most sensitive and reproducible method for detecting mast cells, supporting its inclusion in routine histopathological assessment. The observed T lymphocyte predominance in mast cell-positive, eosinophil-rich cases suggests a potential immunological pattern that may inform future diagnostic and therapeutic strategies. Standardising the evaluation of inflammatory infiltrates and including mast cell and lymphocyte profiling in pathology reports could enhance diagnostic precision and guide patient management in IC/BPS.