Lichen Sclerosus Lesions Research Articles

The Role of Vibrators in Women’s Pelvic Health: An Alluring Tool to Improve Physical, Sexual, and Mental Health

Introduction and hypothesisIn limited studies vibrators have been shown to improve sexual function and pelvic floor health; however, there are even fewer studies on the effect of vibrator use on overall genitourinary and mental health. To investigate the effect of regular vibrator use on sexual, genitourinary, and mental health in addition to quality of life.MethodsWe performed a prospective pilot study of women aged 18 to 80 years recruited from a urogynecology clinic. Study participants were instructed to use a vibrator according to the protocol. Sexual function, pelvic floor function, mental health, and pelvic examination were assessed at the initial visit and at 3 months’ follow-up using validated questionnaires.ResultsOf the 79 participants enrolled in the study, 53 women (66%) completed the study. The mean age of the participants was 54.7 years (range 19–80 years), and the majority of participants were white (n = 59, 74.7%), post-menopausal (n = 48, 60.8%), and not receiving systemic (n = 63, 79.7%) or local (n = 63, 79.7%) hormone therapy. Sexual function significantly improved over time (p = 0.002), whereas the rate of bothersome pelvic organ prolapse symptoms and pain scores significantly decreased (p = 0.034 and 0.0008 respectively). Rates of urge urinary incontinence decreased although this was not statistically significant (p = 0.059). There was a significant improvement in the gross appearance of lichen sclerosus lesions (p = 0.025) and in the severity of vaginal atrophy (p = 0.018). Rates of depression were significantly decreased (p = 0.011).ConclusionsVibrator use was associated with improved sexual, genitourinary, and mental health.

(006) Can Vibrator Use Improve Well-Being?

Abstract Introduction In limited studies vibrators have been shown to improve sexual function and improve pelvic floor health; however, there are even less studies on the effect of vibrator use on overall genitourinary and mental health. Objective This study aimed to investigate the effect of regular vibrator use on sexual, genitourinary, and mental health in addition to quality of life. Methods We performed a prospective pilot study of women aged 18 to 99 years recruited from a urogynecology clinic. Study participants were instructed to use a vibrator for five to ten minutes, two to three times a week for three months on their external genitalia. Sexual function, pelvic floor function, mental health, and pelvic examination were assessed at the initial visit and at three months follow-up using validated questionnaires. Results Of the 79 participants enrolled in the study, 53 women (66%) completed the study. The mean age of the participants was 54.7 years (range 19 – 80 years), and the majority of participants were Caucasian (n=59, 74.7%), post-menopausal (n=48, 60.8%), and not receiving systemic (n=63, 79.7%) or local (n=63, 79.7%) hormone therapy. Sexual function significantly improved over time (p =0.002), while the rate of bothersome pelvic organ prolapse symptoms and pain scores significantly decreased (p=0.034 and 0.0008, respectively). Rates of urge urinary incontinence decreased although this was not statistically significant (p=0.059). There was a significant improvement in gross appearance of lichen sclerosus lesions (p=0.025) and in severity of vaginal atrophy (p=0.018). Rates of depression were significantly decreased (p=0.011). Patients who completed the study were more likely to report having partnered sexual activity (p=0.067), and significantly more likely to have vaginal penetration during intercourse (p=0.017). Conclusions Vibrator use was associated with improved sexual, genitourinary, and mental health. Disclosure No.

VULVAR SQUAMOUS CELL CARCINOMA REVEALED BY PRURITUS

Squamous cell carcinoma of the vulva accounts for 3 to 5% of all female genital cancers. It occurs in women with a history of HPV infection or lichen sclerosus lesions, and in post-menopausal women is also linked to estrogen deficiency. It is generally manifested by a painful, pruritic ulceration on an erythroplastic background on the inner surface of the labia majora. Diagnosis is confirmed by biopsy with anatomical and histological examination. Diagnosis must be made early, and treatment relies mainly on surgery. We report the case of a post-menopausal woman with no pathological history who consulted us for a single symptom: vaginal pruritus.

Vulval Squamous Cell Carcinoma Arising from Lichen Sclerosus Et Atrophicus: A Rare but Not Rear Phenomenon

Genital ulcers may be located on the vagina, penis, anorectal or perineal areas with infectious or noninfectious etiology. Although sexually transmitted infections are a common cause of genital lesions, it is essential to consider nonvenereal disorders such as Behcet’s syndrome, vesiculobullous disease, pyoderma gangrenosum, and malignant tumors in the differential diagnosis. Often, long-neglected benign and premalignant lesions which are hitherto unnoticed may undergo malignant transformation. Herein, we report a woman presenting with recurrent lower urinary tract complaints and a nonhealing ulcer over labia majora, eventually diagnosed with vulval squamous cell carcinoma arising from the underlying lesions of lichen sclerosus et atrophicus. This case emphasizes the importance of early detection and vigilant management of such disorders which may often be asymptomatic and hence remain neglected.

Expression and significance of cyclinD1, cyclin-dependent kinase4 and cyclin-dependent kinase inhibitor P27 in patients with non-neoplastic epithelial disorders of the vulva.

Non-neoplastic epithelial disorders of the vulva (NNEDV) are prevalent and refractory gynecological diseases. However, the underlying pathogenesis of these diseases remain unclear. The present study aimed to investigate the expression and significance of cyclin D1, cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase inhibitor P27 (P27) in patients with NNEDV and provide a reference for clinical diagnosis and treatment. Normal vulvar skin samples from patients with perineum repair (control group, n=20) and skin samples from the vulvar lesions of patients with NNEDV (NNEDV group, n=36) were collected. Expression levels of cyclin D1, CDK4 and P27 were assessed in the samples using immunohistochemistry. The expression of each protein was evaluated based on the mean optical density (MOD). The MODs of cyclin D1 and CDK4 were significantly higher in samples of the three pathological types of NNEDV, namely squamous hyperplasia (SH), lichen sclerosus (LS) and mixed SH and LS lesions, compared with those of the control group. The MOD of P27 was lower in samples of the three pathological types of NNEDV than in the control group, although the difference was not statistically significant. No significant differences in the MOD of cyclin D1, CDK4 and P27 were detected among the three pathological types of NNEDV. The ratios of the MOD of cyclin D1 and CDK4 in the prickle cell layer to those in the basal cell layer were significantly higher in the NNEDV group than in the control group. However, the ratio of the MOD of P27 in the prickle cell layer to that in the basal cell layer exhibited no significant difference between the NNEDV and control groups. NNEDV has the potential for malignant transformation. The occurrence and development of NNEDV may be associated with the acceleration of cell proliferation, in which cyclin D1, CDK4 and P27 contribute to regulation of the cell cycle. Therefore, cyclin D1, CDK4 and P27 may be potential targets in the development of new clinical therapeutic drugs for patients with NNEDV.

Clinical and histopathological spectrum of genital lichen sclerosus in 133 cases: Focus on the diagnosis of pre-sclerotic disease.

Background Early inflammatory lesions of lichen sclerosus are histopathologically difficult to diagnose until the hallmark of the disease i.e., papillary sclerosis becomes visible in histological sections. Pre-sclerotic and late or resolved phases of the disease have not been extensively studied. Methods We retrospectively reviewed all cases diagnosed as genital lichen sclerosus over a ten-year period from 2006 to 2016, correlating the clinical findings with the histological features. Results A total of 133 cases of genital lichen sclerosus (90 males and 43 females) were identified. Both genders demonstrated a similar histological spectrum. Fifty eight (44%) cases were identified as having pre-sclerotic lichen sclerosus, 64 (48%) as having progressive disease and 11 (8%) cases were classified as fully resolved with atrophy. Asymptomatic vitiligoid lesions were identified in 19 (14%) cases of which 12 were male. Low-grade squamous cell carcinoma was seen within the areas affected by long-standing lichen sclerosus, in four patients (3%, 2 male). Limitations We studied only haematoxylin and eosin stained sections. The presence of basement membrane thickening could have been better illustrated with the periodic acid-Schiff stain. Conclusion The pathogenesis of lichen sclerosus probably involves an immune reaction to the basement membrane at the epidermal interface and around the adnexa. The initial band of inflammation shifts gradually downwards from the epidermal interface into the dermis destroying the vascular channels and appendages, resulting in excessive deposition of altered extracellular matrix. Basilar infiltration of lymphocytes along with a grossly vacuolated or thickened basement membrane is proposed as the characteristic diagnostic feature of the pre-sclerotic stage. Greater awareness of the clinicopathological spectrum of lichen sclerosus should enable early diagnosis and treatment, thereby preventing structural damage and possible malignant transformation in chronic cases.

Study of melanocyte density and epidermal thickness in vulvar lichen sclerosus lesions.

This study aimed to analyze changes in melanocyte density and epidermal thickness in vulvar lichen sclerosus (VLS). Vulvar skin tissues were collected from 15 VLS female patients in Beijing Hospital, classified into early (n=7) and late VLS (n=8) groups according to pathological manifestations. Melanocyte density and full epidermal and cell-layer (from the bottom of the stratum corneum to that of the basal layer) thickness were calculated using an image analysis software. The control group was normal vulvar skin tissues from 15 females after plastic surgery. The early VLS (0.170±0.071µm) and late VLS (0.110±0.035µm) groups had significantly lower densities of epidermal melanocytes than the control group (0.275±0.036) (F=36.426, P<0.001). The cell-layer thickness did not differ between the early VLS (154.603±121.984µm) and control (176.974±80.296µm) groups (P=0.899) but significantly decreased in the late VLS group (83.455±37.129µm) compared to the control group (P=0.003). Melanocyte density decreased in early and late VLS. The full epidermal and cell-layer thickness did not significantly change in early VLS, but the cell-layer thickness decreased in late VLS.

Study of Langerhans cells and T lymphocytes in vulvar lichen sclerosus lesions.

The aetiology and pathogenesis of vulvar lichen sclerosus (LS), a chronic inflammatory disease, is not completely clear. It has been found that local cellular immune abnormalities play an important role in the immune mechanism of LS, mainly characterised by abnormal numbers of Langerhans cells in the epidermis and abnormal numbers of dermal T lymphocytes. To evaluate the densities of Langerhans cells and T-lymphocyte subpopulations in vulvar LS. The density of Langerhans cells in the epidermis, and CD3+ , CD4+ and CD8+ T cells in the dermis of seven early-stage and eight late-stage cases of vulvar LS were detected with direct immunofluorescence, and compared with 15 normal controls. The density of Langerhans cells in the late-stage group was significantly higher than in the normal group (P=0.001). The densities of CD3+ , CD4+ and CD8+ T lymphocytes in both the early- and late-stage (deeper dermis) groups were higher than in the normal group (P<0.05). The ratio of CD4+ /CD8+ T lymphocytes in the early-stage and normal groups showed no significant difference (P=0.151), while the late-stage (deeper dermis) groups decreased significantly compared with early-stage, late-stage (upper dermis) and normal groups (P<0.001). The densities of Langerhans cells, CD3+ , CD4+ and CD8+ T cells, and the ratio of CD4+ /CD8+ T lymphocytes were different in different stages of LS, which supports the important role of cellular immunity in mechanisms of LS.

Extra-genital lichen sclerosus reminiscent of cut dragon fruit.

Extra-genital lesions of lichen sclerosus et atrophicus (LS) may occur anywhere on the body. The lesions are polygonal, bluish-white papules that coalesce to become atrophic plaques (2). Prominent, evenly spaced follicular plugs in the atrophic plaques corresponding to obliterated follicular ostia are characteristically seen in the early stages of LS (2). With time, the plugs disappear and leave a smooth, porcelain-white plaque. Dragon fruit is an exotic cactus that is found in Asia, Mexico, and parts of South America (1). The inside pulp of each cut piece of fruit is filled will small seeds that look similar to the follicular plugs of the early stages of LS. The similarities with living beings of dermatological lesions are the basis of many terms such as lupus, herpes etc.

女阴硬化性苔藓皮损黑素细胞和表皮厚度分析

女阴硬化性苔藓皮损黑素细胞和表皮厚度分析

Clonal Relationship Between Lichen Sclerosus, Differentiated Vulvar Intra-epithelial Neoplasia and Non HPV-related Vulvar Squamous Cell Carcinoma

Differentiated vulvar intraepithelial neoplasia (dVIN) and lichen sclerosus (LS) can give rise to vulvar squamous cell carcinoma (VSCC), but genetic evidence is currently still limited. We aimed to determine genetic abnormalities in VSCC and backtrack these abnormalities in the dVIN and LS lesions. DNA from VSCC and patient-matched dVIN and LS samples of twelve patients was collected. High-resolution genome-wide copy number analysis was performed and subsequently, we sequenced TP53. Copy number alterations were identified in all VSCC samples. One dVIN lesion presented with three copy number alterations that were preserved in the paired VSCC sample. Targeted sequencing of TP53 identified mutations in five VSCCs. All five mutations were traced back in the dVIN (n=5) or the LS (n=1) with frequencies ranging from 3-19%. Our data provide genetic evidence for a clonal relationship between VSCC and dVIN or LS.

Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma

PurposeThe two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16.MethodsIn total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data.ResultsTumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups.ConclusionTumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC.

Childhood Phimosis Secondary to Lichen Sclerosus: Is There a Spatial Pattern of Histopathological Changes?

The accurate histopathological diagnosis of the phimotic prepuce is indispensable because early diagnosis, treatment, and close follow-up are crucial in genital dermatosis such as lichen sclerosus (LS). This study analyzes the histopathological spectrum of childhood phimosis with special emphasis on LS. We also highlight a peculiar pattern of histopathological evolution in LS, prepuce. The histopathology slides of all the pediatric preputial circumcision specimens performed for the indication of pathological phimosis (n = 43) during the study period (2012-2017) were analyzed. Eight histopathological features viz. hyperkeratosis, hypergranulosis, epidermal atrophy, acanthosis, dermoepidermal cleft, upper dermal edema and homogenization, mid dermal lymphocytic band, and interface dermatitis were studied in each case, separately in inner preputial surface, tip, and outer preputial surface. On the basis of evolution of the disease and histopathological features, the lesions of LS were classified into early, established, and advanced. LS was found in 32 cases, whereas 11 cases showed nonspecific inflammation and fibrosis. The upper dermal homogenization (n = 29), dermoepidermal cleft (n = 28), and mid dermal band (n = 27) were the commonest histopathological changes. The established and advanced changes were confined to the inner preputial surface (n = 31), and the outer preputial skin surface was unaffected in all the cases. A peculiar histopathological evolution pattern was seen with established or advanced lesions, early lesion, and normal histology on the inner preputial surface, mucocutaneous junction, and outer preputial skin, respectively. LS is a common cause of childhood phimosis. It shows a peculiar histopathological evolution that mandates the thorough analysis of inner mucosal surface.

High-frequency ultrasonography (HFUS) as a useful tool in differentiating between plaque morphea and extragenital lichen sclerosus lesions.

IntroductionMorphea and lichen sclerosus (LS) are chronic inflammatory diseases that may pose a diagnostic challenge for a physician. High-frequency ultrasonography (HFUS) is a versatile diagnostic method utilized in dermatologic practice, allowing monitoring the course of the disease, treatment response and differentiation between certain skin disorders.AimTo prove the usefulness of HFUS in differentiating between plaque morphea and extragenital LS lesions.Material and methodsWe examined 16 patients with plaque morphea and 4 patients with extragenital LS using 20 MHz taberna pro medicum TM (Germany) device.ResultsInvestigations revealed hyperechogenic entrance echo in both morphea and LS lesions, whereas a distinct polycyclic surface of the entrance echo was detected exclusively in LS.ConclusionsHigh-frequency ultrasonography is a current diagnostic modality that may prove useful in differentiating between morphea and LS lesions.

Reduction in ERRα is associated with lichen sclerosus and vulvar squamous cell carcinoma

ObjectiveERRs (estrogen-related receptors) regulate energy metabolism, the cell cycle and inflammatory processes in both normal and cancer cells. Chronic inflammation induced by lichen sclerosus (LS) or human papilloma virus (HPV) precedes vulvar squamous cell carcinoma (vulvar SCC). We investigated the expression of ERRα, ERRβ and ERRγ in normal vulvar skin, LS as well as LS-dependent and LS-independent/HPV-related vulvar SCC. MethodsA total of 203 samples were analyzed for ERRα, ERRβ and ERRγ by using immunohistochemistry. These included 37 normal vulvar skin samples, 110 LS samples, 6 vulvar intraepithelial neoplasia (VIN) samples and 50 vulvar SCC samples. ResultsA substantial reduction in or disappearance of ERRα was detected in all vulvar SCC samples. A total of 79% of childhood-onset LS and 51% of adulthood-onset LS lesions showed decreases in ERRα staining. A gradual reduction in ERRα cytoplasmic staining was observed from healthy vulvar skin to precursor lesions and further to SCC. Nuclear ERRα staining was observed in 8/33 (24%) LS-dependent and 10/17 (59%) LS-independent SCC samples. ConclusionsERRα, a key regulator of cell energy metabolism, may play a role in the pathogenesis of both LS and vulvar SCC.

Eosinophils in biopsy specimens of lichen sclerosus: a not uncommon finding.

Evolving lesions of lichen sclerosus (LS) pose a diagnostic challenge owing to an absence of classic findings of epidermal atrophy, dermal sclerosis, a band-like lymphocytic infiltrate and the presence of eosinophils. Retrospective specimens of LS were reviewed. Demographic information, biopsy vs. excision and the following histopathological characteristics were noted: presence and number of eosinophils, epidermal hyperplasia, spongiosis, early/transitional LS, well-developed LS and coexisting squamous cell carcinoma (SCC). Linear regression analysis was performed. The data consisted of 66 biopsies (36 male [M], 30 female [F]), from 53 individuals (33M, 20F), including 57 genital and 9 extragenital biopsies. Seven biopsies showed SCC, 28 showed epidermal hyperplasia and 14 exhibited spongiosis. Thirty-five specimens were early/transitional LS and commonly exhibited epidermal hyperplasia (57%), epidermotropism of lymphocytes (97%) and basement membrane thickening (97%). Thirty-five biopsies (53%) contained eosinophils (23 early/transitional lesions). Male gender (p = 0.074) was associated with increased eosinophils. The presence of SCC (p = 0.014) was a significant predictors of eosinophil number. Epidermal hyperplasia, epidermotropism of lymphocytes and basement membrane thickening are helpful features in identifying early LS. Eosinophils are not an uncommon finding in LS and are most common in male genital lesions and in LS associated with SCC.

Outcome of 1-Stage Urethroplasty Using Oral Mucosal Grafts for the Treatment of Urethral Strictures Associated With Genital Lichen Sclerosus

To report the outcome of 1-stage urethroplasty using lingual mucosal grafts (LMGs) and buccal mucosal grafts (BMGs) for the treatment of male urethral strictures associated with genital lichen sclerosus (LS). This was a descriptive, observational retrospective study of male patients with urethral strictures who underwent 1-stage mucosal graft urethroplasty using different substitute materials for reconstructive urethral surgery. Study inclusion criteria were patients with histologically proven LS presenting with urethral strictures. Exclusion criteria were patients without histologically proven LS, traumatic strictures, failed hypospadias, and malignant lesions. Successful reconstruction was defined as normal voiding with a peak flow >12mL/s, no obstructive symptoms, and no postoperative procedure, including dilation. Between January 2003 and December 2011, urethral strictures in 54 patients were considered associated with genital LS according to the inclusion and exclusion criteria, and 36 underwent 1-stage urethroplasty using oral mucosal grafts. The median age was 52years (range, 32-80years). The median stricture length was 12.5 ± 1.6cm (range, 6-18cm). One-stage single-sided dorsal LMG urethroplasty was performed in 22 of 36 patients. The remaining 14 patients received the same procedure combined with dual BMGs (n= 5) or with LMG combined with BMG (n= 9). The success rate was 88.9%. Postoperative urinary fistula occurred in 1 patient, and meatal stenosis developed in 3 patients. Mean follow-up was 38.7months (range, 12-110months). Our survey suggests that 1-stage urethroplasty with single or combined LMGs or BMGs may be aneffective option to treat urethral stricture associated with LS.

Phosphorylated S6 as an immunohistochemical biomarker of vulvar intraepithelial neoplasia

As life expectancy lengthens, cases of non-viral-associated vulvar squamous cell carcinoma and its precursor lesion, so-called differentiated vulvar intraepithelial neoplasia (VIN), continue to increase in frequency. Differentiated VIN often is difficult to recognize and failure to detect it before invasion results in morbidity and mortality. Thus, identification of a reliable biomarker for this type of lesion would be of great clinical benefit. Our recent studies have identified activation (ser235/236 phosphorylation) of ribosomal protein S6 (p-S6) in basal epithelial cells as an event that precedes and accompanies laminin γ2 overexpression in most preinvasive oral dysplasias. To test this as a potential biomarker of vulvar dysplasia, we immunostained seven differentiated VINs and nine papillomavirus-related ‘classic’ VINs, most of which were associated with carcinoma, for p-S6. All carcinomas, all differentiated VINs, and most classic VINs contained regions of p-S6 staining in the basal layer, whereas basal and parabasal cells of normal vulvar epithelium and hyperplastic and inflamed lesions lacking cellular atypia were p-S6 negative. Laminin γ2 was expressed in a subset of VINs, always occurring within basal p-S6 positive regions, as we had found previously for oral dysplasias. Lichen sclerosus is considered a potential precursor of vulvar carcinoma. Two lichen sclerosus lesions of patients with a concurrent carcinoma and one of six lichen sclerosus lesions without atypia or known concurrent carcinoma were basal p-S6 positive. In summary, there is a distinct difference in p-S6 basal cell layer staining between benign and neoplastic vulvar squamous epithelium, with consistent staining of differentiated VIN and of some lichen sclerosus lesions. These results support further studies to assess the potential of p-S6 as a biomarker to identify vulvar lesions at risk of progressing to invasive cancer.

Dermoscopy of atypical lichen sclerosus involving the tongue

Involvement of tongue during the course of lichen sclerosus is extremely rare, with only five - to our knowledge - described cases in the English literature. We present clinical and dermoscopic findings of a female patient who concomitantly developed genital, skin and oral lesions of lichen sclerosus. Tongue involvement consisted of a linear atrophic whitish plaque, strikingly mimicking "en coupe de sabre" scleroderma. Dermoscopic examination revealed a well demarcated, linear, dense, white, homogenous area, with papillae projections hardly seen in the affected area. Dermoscopy of lesions located on the trunk revealed whitish plaques with comedo-like openings in the center and an erythematous halo at the periphery. Since clinical differentiation of oral LS and other oral diseases appearing as white atrophic plaques is almost impossible without using histology, we believe that dermoscopy might represent an additional tool, contributing to the final diagnosis, and thus avoiding an ablative procedure at this site-sensitive localization.

Claudin and p53 expression in vulvar lichen sclerosus and squamous-cell carcinoma

AimsVulvar squamous-cell carcinoma (SCC) is a rare gynaecological cancer. Vulvar SCC has been shown to develop from vulvar intraepithelial neoplasias, which are related to lichen sclerosus (LS). Most studies to...