Histopathology of Anterior Urethral Strictures: Toward a Better Understanding of Stricture Pathophysiology

Abstract

Introduction: Histopathology can provide insights into disease mechanism, but to date has been poorly described in urethral strictures. The purpose of this study was to comprehensively describe the histopathologic findings from stricture specimens obtained at the time of anterior urethroplasty (AU). Methods: All pathologic specimens from men undergoing AU for USD from 2010-2017 at a single institution were re-reviewed by a single, blinded pathologist who was directed to rule out lichen sclerosus (LS) and then describe inflammatory cell type and severity when present. Cohorts comprised of strictures with no inflammation, minimal to mild inflammation, or moderate to severe inflammation were developed and stricture, patient and surgical outcome characteristics were compared. Results: Histopathology slides from 100 AU cases were reviewed. Two or more LS characteristics were present in 21% of specimens and 44% of specimens showed chronic inflammation (minimal 20%, mild 39%; moderate 39%; severe 2%). Lymphocytes (86%) and plasma cells (12%) were the predominant cell type. Patients with inflammatory strictures reported worse overall health. Inflammation was largely absent from isolated bulbomembranous strictures (9%) and more common in LS strictures (100%). The overall failure rate of 11% was not affected by the presence (7%) or absence (14%) of inflammation. Conclusions: Chronic inflammation is prevalent in a significant percentage of USD specimens. Associations with worse overall health suggest systemic mediators. Absence of inflammation in bulbomembranous strictures suggests a unique pathophysiology in this region. The presence of inflammation did not affect surgical outcomes at medium-term follow-up.

Synchronous genitourinary lichen sclerosus signals a distinct urinary microbiome profile in men with urethral stricture disease

“…While an infectious etiology of LS has been actively studied, there is no consensus that bacterial infection is a cause [10]. While some groups have implicated Borrelia burgdorferi [25], evidence is ultimately poor with an unknown direction of association.…”

“…One poorly understood inflammatory condition that negatively impacts the male urethra is genitourinary lichen sclerosus (LS) [10]. LS is a chronic, inflammatory condition of unknown etiology that can result in urethral stricture disease (USD) [11].…”

Ectopic Germinal Centres with B and T Cells and Follicular Dendritic Cell Networks in Urethral Stricture Tissue: Possible Avenue for Immunological Treatments

“…The hypothesis that lichen sclerosus could be a cause of GCs in bulbar urethral strictures was challenged by a study that found that lichen is almost always situated in the penile urethra rather than in the bulbar region [25] , [26] .…”

Effects of Anti‐Inflammatory Nanofibers on Urethral Healing

“…[ 19 ] Causes of strictures include poor vascularization resulting in contracture of buccal or skin grafts used or increased local inflammation. [ 20 ] Mechanisms to modulate the inflammatory process during urethral healing would help reduce the risk of this postoperative complication and decrease patient morbidity. This may be achieved with intraoperative application of anti‐inflammatory nanofibers to the urethroplasty to enhance the postoperative healing process.…”