Introduction: Nearly 50% of anterior urethral strictures are of idiopathic etiology. To investigate the underlying biology of idiopathic strictures, we compared inflammatory profiles of idiopathic strictures with those of known etiology, specifically trauma/iatrogenic strictures and lichen sclerosus strictures. We hypothesized that each group would contain distinct inflammatory features. Methods: Five centers prospectively enrolled patients into an NIDDK-funded study evaluating inflammation in anterior urethral stricture disease. Subjects underwent standard urethroplasty per surgeon routine and tissue was sent to a centralized repository. H&E-stained sections of stricture tissue and stricture-adjacent urethral tissue (1 cm from stricture when available) were examined by a single, blinded pathologist and evaluated for degree of inflammation and primary inflammatory cell type. Results: 133 strictures were analyzed: trauma/iatrogenic (n=32), idiopathic (n=74), and lichen sclerosus (n=27). Inflammatory cells were present in 40.6% of trauma/iatrogenic samples, 63.5% of idiopathic samples, and 59.3% of lichen sclerosus samples [A]. Stricture-adjacent urethral tissue was collected from 44 subjects with inflammation in their strictures. Stricture-adjacent tissue from 38 of these subjects (81.8%) contained inflammation [B]. Degree of inflammation was higher in idiopathic strictures than in trauma/iatrogenic strictures (1.42 vs 0.81, 5-point Likert scale, p=0.049) [C]. Idiopathic and lichen sclerosus strictures were similar in degree of inflammation (1.42 and 1.41, respectively, p>0.999) and the distribution of inflammation severities among samples. The predominant inflammatory cell types in idiopathic strictures resembled trauma/iatrogenic strictures [D]. Conclusions: Anterior urethral strictures display etiology-specific patterns of inflammation severity and composition. Though remote trauma is often postulated as the cause of idiopathic strictures, pathologically they resemble the pattern of chronic inflammation seen in lichen sclerosus strictures, suggesting potential overlap in underlying pathophysiology. SOURCE OF Funding: NIDDK 1R21DK115945-01
