Lichen Sclerosus of the Urethra, Penile Skin and Vulva: 3 Distinct Disease Processes
Alison Levy, MD1; Kristian Stensland, MD1; Jennifer Bennett, MD1; Brendan Browne, MD1; Ariel Fredrick, MD1; Travis Sullivan, PhD1, Jason Badrinarain, MSc2, Jorge Yao, MD2; Kimberly Rieger-Christ, PhD1, Alex Vanni, MD1
1Lahey Hospital, Burlington, MA; 2Pathline Emerge, Ramsey, NJ
Lichen Sclerosus (LS) is a chronic, inflammatory skin condition that affects men and women with predilection for the genital regions. Despite identical pathologic diagnostic criteria, the clinical course of LS in men and women differs. The disease in men is heterogeneous, as 30% who present with genital LS will develop urethral stricture disease (USD). Prior research has aided in characterization of vulvar LS but no large-scale studies have focused on LS of the male urethra or genital skin. Our hypothesis is that male LS is distinct from female LS. We sought to compare protein expression in pathologically confirmed male urethral, male genital, and female LS samples.
Tissue samples were collected at a single institution from male genital skin, urethral strictures and female genital skin with confirmed LS. Chart review was performed to extract clinical and demographic data. In-house pathologists reviewed paraffin slides to identify areas of interest that appeared pathognomonic for LS. A tissue microarray (TMA) was created with cores from each sample. Markers of inflammation, cell cycle disruption, oxidative stress, hormone receptor, and viral infection were selected and immunohistochemistry was performed on the TMA. Stains were evaluated semiquantitatively or qualitatively, as appropriate. Data were compared by Kruskal-Wallis or Fisher's exact test with significance of alpha=0.05.
Core samples were analyzed from 58 men with LS USD, 19 men with genital LS and 6 women with genital LS. Female LS samples stained more for p53 compared to male LS USD. Only male LS showed loss of cyclin D1 presence and only male genital LS showed loss of GH2AX expression. Block-like p16 staining, which is associated with high-risk HPV, was seen only in the male LS USD and genital skin LS samples. Thirty-seven percent of male LS USD and 27% of male genital skin LS stained positively for EBV versus none of the female LS samples. LS USD from males expressed significantly higher levels of VEGF compared with female LS (p<0.001) and male skin LS (p<0.01). Approximately half of male LS samples had loss of androgen receptor expression. There was no difference in staining for markers of inflammation.
Immunohistochemistry staining demonstrates differences in the pathophysiology of male genital LS, LS USD, and female genital LS suggesting that they may be distinct disease processes. Our results indicate that there may be alteration of cell cycle regulation in LS USD and more significant oxidative stress in male LS. EBV and block-like p16 stains show that there may be an infectious precursor to the formation of male LS. Larger cohorts and further study are needed to fully elucidate the pathophysiology of LS.
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