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.

Basal cell adenoma and basal cell adenocarcinoma represent basaloid salivary gland neoplasms that show cyto-morphologic similarity but differ at the histologic level by their invasive qualities, as adenocarcinomas show invasion beyond their capsule, a finding not seen in the adenomas. Due to the low incidence of these tumors, the molecular mechanism underlying their pathogenesis is poorly understood. We sought to further delineate these neoplasms through mutation profiling by targeted next-generation sequencing (NGS). Twenty cases (basal cell adenocarcinoma = 10; basal cell adenoma = 10) were retrospectively selected from a previous analysis. NGS was performed using the Ion AmpliSeq™ Cancer Hotspot Panel v2 (Life Technologies, Carlsbad, CA). The data was analyzed using the Ion Torrent Suite Software (Life Technologies) followed by a laboratory-developed pipeline. One of eight cases of basal cell adenocarcinoma had a mutation, which was an activating mutation in PIK3CA (c.3140A>G, p.H1047R). No mutations were detected in the remaining basal cell adenocarcinomas. In the basal cell adenomas, the CTNNB1 p.I35T mutation was identified in three of nine (3/9) cases. A missense mutation in the ATM gene (c.2572T>C, p.F858L) was seen in a basal cell adenoma with an allele frequency of 53 %, raising the possibility of a germline mutation. The overall findings suggest that although there is cytomorphologic similarity, differences exist between these two tumors at the histologic and genetic level. Although the numbers of cases are limited, the aberrations in genes affecting different signaling pathways in the basal cell adenocarcinoma versus the basal cell adenomas suggest that basal cell adenocarcinoma likely arises de novo and not from basal cell adenoma.

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count in periurethral tissues. Our results provide a rationale for a mechanistic relationship between low testosterone levels and subsequent decreased periurethral vascularity. We believe that this results in urethral atrophy conferring a higher risk of AUS erosion.

suggest that HIFU urethral complications may be particularly disabling and this issue deserves further investigation.