Perineural Inflammation as a Novel Feature in Lichen Sclerosus: A Case Series of Histologic and Clinical Features.

ABSTRACT: Lichen sclerosus (LS) is a frequently encountered inflammatory skin disorder characterized by whitened, atrophic patches that can cause pain and pruritus. The underlying cause of this condition remains unknown. Primarily affecting the genital area, this condition carries an increased risk of developing cutaneous cancers and frequently co-occurs with autoimmune disorders. Our retrospective study aimed to explore histologic features of LS, with a particular focus on a newly established finding and its potential implications. We examined 53 histologic cases of LS collected over 2 years. Experienced pathologists evaluated and reached a consensus on the assignment of histologic features. Patient charts were manually reviewed to gather relevant demographic and clinical data. Statistical analysis was performed using IBM SPSS Statistics (2021). Of the 53 total patients identified as meeting criteria for inclusion in this study, only 8 (15%) were male. Eight cases (15%) demonstrated perineural inflammatory infiltrate. Notably, half of all samples from male patients exhibited perineural inflammatory infiltrate. A statistically significant increase ( P < 0.01) in the presence of dermal plasma cells was identified in cases with perineural inflammation versus cases without this feature. The findings of our study highlight the recurrent nature of perineural inflammation in LS, providing valuable insights into this condition. Furthermore, we observed a notable correlation between perineural inflammation, male patients, and the presence of dermal plasma cells. These discoveries contribute to a better understanding of the underlying mechanisms of LS and suggest avenues for future research into the condition.

Vulvar Lichenoid Dermatoses With Emphasis on the Distinction Between Lichen Sclerosus and Lichen Planus: A 10-Year Study.

OBJECTIVES: Lichen planus (LP) and lichen sclerosus (LS) are the most common vulvar lichenoid dermatoses. The diagnostic challenges are due to site-specific variation in microscopic appearance and small-sized biopsies. Authentication of diagnostic criteria to distinguish LS and LP to uncover any resemblance or divergence in presentation of these conditions is attempted. METHODS: Cases of vulvar LP and LS diagnosed between January 2012 to December 2022 were included. The clinical details included age, presenting symptoms, examination findings, and other organ involvement. Histopathological analysis of epidermal, dermal, and adnexal findings was done. RESULTS: There were 28 cases of vulvar LP and 72 cases of LS, with a median age of 51 and 60 years, respectively. Depigmentation and atrophy were the major clinical features in LS, whereas ulcers/erosions and erythema were more prevalent in LP with a significantly higher incidence of oral involvement. The most diagnostic feature in LS was diffuse dermal sclerosis (76.8%) and interstitial pattern of inflammation (81.4%), whereas the characteristic features in LP cases was a lichenoid pattern of inflammation (85.7%), necrotic keratinocytes, and lymphocytic exocytosis. In 44.4% of LS, unconventional features like compact orthokeratosis, parakeratosis, thickened/wedge-shaped hypergranulosis, and sawtooth rete pegs were noted. Lichen sclerosus with lichenoid inflammation (21.4%) mimicked LP, from which it was distinguished by presence of thickened or diminished granular layer with basal melanin absence (60%) and dermal homogenization (80%). CONCLUSION: Although the classical, well-established variant of LS poses no diagnostic difficulty, the unconventional variant may mimic LP. Identification of the subtle histological clues demonstrated in this study can help to arrive at the correct diagnosis.

Well-differentiated Squamous Cell Carcinoma With Sarcomatous Differentiation in Patient With a History of Recurrent Verrucous Carcinoma.

Human papillomavirus-independent vulvar squamous cell carcinoma has a peak incidence in about the eighth decade of life. A variable portion of the vulvar squamous cell carcinoma are human papillomavirus-independent comprising 20% to 80% of all cases. Verrucous carcinoma (VC) is part of the spectrum of human papillomavirus-independent carcinomas and its combination with well-differentiated squamous cell carcinoma with sarcomatous differentiation is an extremely unusual neoplasm. The available literature on VC is currently limited to case reports and small single-institution studies. Here, we present a case concerning an 81-year-old woman with a history of chronic itching, swelling, and lichen sclerosis with variable-sized multiple white-pink plaques of the vulva. The pathologic diagnosis of VC was made. The patient later on developed multiple lesions of biopsy proved VC and most recent biopsy shows well-differentiated squamous cell carcinoma with abrupt sarcomatous differentiation. A review of the literature shows the rarity of this lesion of the female genital tract. Clinicians and patients should be aware of the aggressive behavior of cancers and adjust their surgical management together with the follow-up strategy. To the best of our knowledge, this is the first description of a VC and well-differentiated squamous cell carcinoma with abrupt sarcomatous differentiation occurring in the vulva.

Topical 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) for lichen sclerosus of face: case report and literature review.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis typical of the genital region, with rare involvement of extragenital areas and particularly the face. LS therapeutic management is challenging, and common therapies including topical and systemic corticosteroids, topical calcineurin inhibitors, surgery are often ineffective. Herein, we present a case of LS occurred in a 36-year-old girl with facial involvement resistant to therapy with systemic corticosteroids and topical tacrolimus. Considering the involvement of a sensitive area, the young age of the patient, and the consistent clinical experience in using photodynamic therapy for the treatment of facial skin disease, we started a treatment with topical 5-aminolevulinic acid (ALA)-photodynamic therapy (PDT) with a dosage of 37 J/cm2 once a month. We compared our case with eight other facial LS patients from the literature and treated differently.

[Lichen sclerosus in clinically relevant phimosis: incidence, risk factors, and association with squamous cell carcinoma of the penis]. / Lichen sclerosus bei klinisch relevanter Phimose: Häufigkeit, Risikofaktoren und Assoziation mit Plattenepithelkarzinomen des Penis.

BACKGROUND: Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin disease. It is frequently diagnosed following circumcision. Diabetes mellitus (DM) is a known risk factor in men. Malignant pathology is more common in patients with LSA. Data on LSA in men are very limited. OBJECTIVE: This study investigated the incidence of LSA in men who had undergone circumcision. Risk factors and likelihood of malignancy were captured. MATERIALS AND METHODS: Data of 215 patients were retrospectively analyzed. As potential risk factors, age, body mass index (BMI), DM, coronary heart disease (CHD) and arterial hypertension were identified. Data were analyzed and displayed graphically as spike histograms. Logistic regression was applied. Age and BMI were transformed using cubic spline function. RESULTS: Mean age of patients was 37 years (±â€¯22 years). Mean BMI was 26.4. In all, 24% of the patients had a BMI > 30. Of the patients, 11% had DM, 5.1% had CHD, and 19% had arterial hypertension. Pathology revealed LSA in 47% of patients. Malignant disease was apparent in 3.3% of patients (2.7% without concomitant LSA, 4% with concomitant LSA). Age (55 vs 20 years, odds ratio [OR]: 3.210 [1.421, 7.251]) was a significant risk factor for LSA. BMI (30 vs 22 kg/m2, OR 1.059 [0.614, 1.828]) and DM (OR: 0.42 [0.148, 1.192]) elevated the risk for LSA. CONCLUSION: We saw high rates of LSA in patients had undergone circumcision. Higher age represents a significant risk factor. In 3.3%, final pathology revealed squamous cell carcinoma of the penis. Therefore, pathologic work-up of circumcision specimen is mandatory.

Combination of high-frequency electrocautery therapy and ALA-PDT in hyperkeratotic vulvar lichen sclerosus: Series of seven cases.

SIGNIFICANCE: ALA-PDT effectively treats Vulvar lichen sclerosus et atrophicus (VLSA), but it requires multiple repetitions for satisfactory results. To enhance efficacy, we employed a combination of high-frequency electrocautery therapy and ALA-PDT in treating seven VLSA patients. APPROACH: Lesions and leukoplakia in the seven women with VLSA were removed using a high-frequency generator. PDT was administered after wound healing, and it was repeated six times. Follow-up assessments were carried out at 1, 3, and 6 months to evaluate the severity of pruritus and investigate lesion repigmentation. RESULTS: Following the combined therapy, the disappearance of pruritus was observed in all patients, and normal color and thickness were restored to their skin. Two patients reported mild pruritus with a score of 2 one month after treatment, which persisted until the 6-month follow-up, while the remaining patients remained free from pruritus. No recurrence of skin lesions was observed in any of the patients. CONCLUSIONS: The combined therapy for the treatment of VLSA is found to be convenient, effective, and easily promotable.

Prevalence of prescribing topical corticosteroids to patients with lichen sclerosus following surgery for vulvar cancer: a survey among gynaecologic oncologists in The Netherlands.

BACKGROUND: Vulvar lichen sclerosus (LS) is a chronic inflammatory dermatosis which can progress to precursor lesion differentiated vulvar intraepithelial neoplasia (dVIN) and vulvar squamous cell carcinoma (VSCC). The risk of developing recurrent vulvar cancer following LS-associated VSCC is high. Evidence suggests that treatment of LS with topical corticosteroids (TCS) can prevent progression to dVIN, VSCC and recurrences. However, current guidelines do not give any recommendation on the management of LS following surgery for VSCC. The aim of this study was to conduct a survey among all registered gynaecologic oncologists (GOs) in the Netherlands to evaluate the current management of LS patients without a history of VSCC (LSnoVSCC) and patients with LS following surgery for VSCC (LSVSCC). METHODS: An online survey was distributed to all registered GOs in the Netherlands. Primary outcome measures were the frequency, type and duration of TCS treatment prescribed for LSnoVSCC and LSVSCC patients, separately. As a secondary outcome measure, reasons for treating or not treating patients with LSnoVSCC and LSVSCC with TCS were analysed. RESULTS: Forty-four GOs completed the survey, resulting in a response rate of 75%. TCS were prescribed more often to patients with LSnoVSCC as compared to patients with LSVSCC (86% versus 52%, respectively, p < 0.001). If treatment was initiated, ultra-potent (class IV) TCS were most commonly prescribed for an indefinite period of time for both patient groups. The most reported reason for treating patients in both groups with TCS was symptoms, followed by clinical aspects of the lesion and prevention of progression to dVIN and VSCC. CONCLUSION: The majority of GOs who participated in our study endorse the utilisation of long-term ultra-potent TCS therapy in both patients with LSnoVSCC and LSVSCC. Nevertheless, Dutch GOs are currently prescribing TCS more frequently to patients with LSnoVSCC than to patients with LSVSCC.

Vulvar lichen sclerosus (LS) is a chronic skin condition which may progress to vulvar squamous cell carcinoma (VSCC) through differentiated vulvar intraepithelial neoplasia (dVIN). LS symptoms are treated with topical corticosteroids (TCS), which can also prevent progression to dVIN and VSCC. However, current international guidelines do not give any recommendation on the treatment of LS following surgery for VSCC. To evaluate the current management of LS patients without a history of VSCC (LS^noVSCC) and patients with LS following surgery for VSCC (LS^VSCC), a survey study was conducted among all gynaecologic oncologists (GOs) in The Netherlands. The findings of this study demonstrate that Dutch GOs prescribed TCS more often to patients with LS^noVSCC as compared to patients with LS^VSCC. However, when deciding to prescribe TCS, the majority of Dutch GOs prescribed ultra-potent TCS for an indefinite period of time for both LS^noVSCC and LS^VSCC patients.

[Genital lichen sclerosus and lichen planus]. / Genitaler Lichen sclerosus und Lichen planus.

Lichen sclerosus (LS) and lichen planus (LP) are chronic inflammatory dermatoses of unknown aetiology. They pose the most important differential diagnoses of inflammatory dermatoses in the genital area. There is often a delay in diagnosing LS and LP and subsequently treatment is initiated late in the course of the disease, which will lead to scarring and a decreased quality of life. There is an increased risk of the development of malignancies in the genital area in both diseases; however, early and continuous treatment with potent topical steroids will decrease this risk.

Affirming Long-Term Outcomes After Contemporary Urethroplasty: The Adverse Impact of Increasing Stricture Length, Lichen Sclerosus, Radiation, and Infectious Strictures.

PURPOSE: There is a paucity of reported long-term outcomes after contemporary urethroplasty. Our objective is to determine the long-term success of modern urethroplasty and identify factors associated with stricture recurrence in this context. MATERIALS AND METHODS: Patients undergoing urethroplasty from July 2003 to May 2013 with at least 100 months of follow-up were identified. Long-term outcomes including stricture recurrence and patient satisfaction were evaluated by review of regional/provincial electronic records and telephone interview. Urethroplasty failure was defined as a recurrent stricture (<16F) confirmed on cystoscopy. Cox regression was used to evaluate variables associated with long-term stricture recurrence. RESULTS: A total of 733 patients were identified with ≥ 100 months follow-up. Median patient age was 45 years, stricture length was 4.7 cm, and 85.8% failed prior endoscopic treatment. At a median follow-up of 12.3 years, 89 recurrences were observed. Cumulative incidence of stricture recurrence was 6%, 10%, and 12% after 1, 5, and 10 years, respectively. From a patient-reported perspective, 89% of patients reported being satisfied with the outcome of surgery. On multivariable analyses, increasing stricture length (HR 1.1, 95% CI 1.05-1.15; P < .001) and stricture etiology (P < .001), in particular lichen sclerosus (HR 4.46, 95% CI 2.25-9.53), radiation (HR 4.25, 95% CI 1.65-10.9), and infectious strictures (HR 5.27, 95% CI 2.03-13.7), were independently associated with stricture recurrence. CONCLUSIONS: This study affirms the widely held belief that modern urethroplasty provides high long-term patency and patient-reported satisfaction. Patients with longer strictures as well as those with lichen sclerosus, radiation, and infectious etiologies have a higher hazard of stricture recurrence in the long term.

Lichen sclerosus associated with Turner syndrome treated with photodynamic therapy: A case report.

Turner syndrome (TS) is a rare clinical condition associated with a completely or partially absence, or structural abnormality of an X chromosome, mainly representing as short stature and skeletal anomalies, female hypergonadotropic hypogonadism and infertility. Skin is frequently involved in TS, especially autoimmune diseases like vitiligo and lichen sclerosus (LS). Here, we present a 10-year-old Chinese girl with TS combined with both vulvar LS (VLS) and extragenital LS, who had been misdiagnosed as eczema and vitiligo for years. In order to control LS sufficiently and allay the parents' concerns of potential side effects of topical corticosteroids, she was prescribed with tacrolimus ointment on the extragenital lesions, and photodynamic therapy (PDT) for vulvar lesions. For PDT regimen, we used 5-aminolevulinic acid (ALA) as photosensitizer and 633 nm red light to irradiate the lesion area at 60 mW / cm2 for 30 min each time. After 6 times of treatment at 2-week intervals, a satisfactory remission of both pruritus and lesion severity was achieved. So far, the guideline on TS did not include LS as a common comorbidity to raise attention. However, accurate diagnosis and effective treatment are essential for LS to avoid the possibilities of developing labial atrophy, adhesion, or even vulvar cancer. Based on our research, PDT can significantly relieve subjective symptoms, objective lesion severity and histopathological changes of VLS with good tolerance, and therefore can also be a safe and effective therapeutic alternative in such comorbidity in TS patients.

Comorbidity in patients with Lichen sclerosus: a retrospective cohort study.

Lichen sclerosus (LS) is a chronic lymphocyte mediated inflammatory mucocutaneous disease of unknown aetiology with a predilection for the anogenital region, and affecting both sexes. The disease is characterized by pain, intolerable itching and scarring. In late stages of LS, disfiguring scarring can drastically alter the structural anatomical architecture of the genitals. The association between genital LS and different malignant tumours is a concern that needs to be further investigated. An association between LS and several autoimmune diseases has been confirmed in recent studies. All registered citizens of Region Jönköping, Sweden were included in the present study. Patients diagnosed with LS (n = 5680) between 2001 and 2021 were identified using ICD-10 code L90.0 and selected as cases. All other individuals (n = 362 568) served as controls. Odds ratios (ORs) for the selected comorbidity were calculated and adjusted for age and sex. The cumulative incidence of LS for the entire population over a 20-year period was 1.54% (15.4 per 1000 people). The cumulative incidences over a 20-year period for females and males were 2.13% and 0.97%, respectively. This study confirmed the association between LS and vulvar cancer (OR = 17.4; 95% CI 12.1-25.3), penis cancer (OR = 9.1; 95% CI 4.3-18.9), prostate cancer (OR = 2.0; 95% CI 1.6-2.4) and breast cancer (OR = 1.6; 95% CI 1.4-1.8). LS was also associated with Crohn´s disease (OR = 2.0; 95% CI 1.6-2.6) and diabetes mellitus type 1 (OR = 1.9; 95% CI 1.6-2.1). The present study revealed novel important data regarding the association of LS with cancer and autoimmune diseases, emphasising the importance of sufficient treatment and follow-up of patients with LS. However, future studies are needed to confirm these results and the potential role of LS in the development of cancer.

Comorbidities in Male Patients With Lichen Sclerosus: A Case-Control Study.

OBJECTIVE: Lichen sclerosus (LS) is a chronic inflammatory skin disease. In male patients, it usually involves the glans penis and foreskin and can cause phimosis or meatal stenosis. The aim of this cross-sectional case-control study was to identify clinically important comorbidities in male patients with LS. MATERIALS AND METHODS: By searching Turku University Hospital electronic health records, the authors identified 630 male patients diagnosed with LS between 2004 and 2020. To investigate possible comorbidities, the authors compared this patient group to a 10-fold larger control group. RESULTS: The incidence of LS increased during the study period, from 5 to 27.5 per 100,000 men. Patients were most often diagnosed at 21 to 25 years of age. Patients with LS exhibited markedly increased risks of penile carcinoma (odds ratio [OR], 81.0; 95% CI = 10.82-3516.7; p < .001) and carcinoma in situ of the penis (OR = 60.5; 95% CI = 7.32-2738.9; p < .001). Patients also more commonly exhibited lichen planus (OR = 16.8; 95% CI = 8.97-32.39; p < .001), psoriasis (OR = 3.3; 95% CI = 1.80-5.70; p = .004), angina pectoris (OR = 1.8; 95% CI = 1.10-2.81; p = .013), obesity (OR = 2.6; 95% CI = 1.72-3.77; p < .001), type 2 diabetes (OR = 2.3; 95% CI = 1.74-3.09; p < .001), and hypertension (OR = 1.9; 95% CI = 1.53-2.37; p < .001). The most commonly performed urological procedures were operation for phimosis, uroflowmetry, and ultrasound measurement of residual urine. CONCLUSIONS: Genital malignancies, other dermatological conditions, and diseases related to metabolic syndrome should be considered when treating patients with LS.

Idiopathic Lichenoid and Granulomatous Vulvitis: A Distinct Clinicopathological Entity.

ABSTRACT: The combination of lichenoid and granulomatous inflammation is uncommon in vulval biopsies. We present a series of 5 patients with lichenoid and granulomatous vulvitis, presenting with clinical changes resembling lichen sclerosus. Despite detailed clinicopathological investigation and follow-up, there was no apparent association with an underlying recognized cause. All 5 cases occurred in postmenopausal women and displayed a distinctive histological pattern of superficial band-like inflammation with granulomas "anchored" to the dermoepidermal junction. There was no evidence of deeper granulomatous inflammation. Despite repeated biopsies over 2 years in 2 patients, neither developed typical histological features of lichen sclerosus. We postulate that idiopathic lichenoid and granulomatous vulvitis may represent a distinct clinicopathologically defined vulvar dermatosis.

Reflectance confocal microscopy features of vulvar lichen sclerosus in Chinese juvenile girls.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unknown pathogenesis, characterized by porcelain-white atrophic plaques around the vulvar and anal areas in girls. With this communication, we performed the study on 16 female girls with clinically and histologically confirmed VLS, described the main identifying characteristics of the lesions in reflectance confocal microscopy (RCM) and elucidated the corresponding relationship between RCM findings and histology. We recommend RCM, a noninvasive technique, as a complementary diagnostic tool for VLS.

Fat Grafting in Vulvar Lichen Sclerosus: Long Term Follow-Up.

OBJECTIVE: The rationale for the use of autologous fat grafting in the treatment of vulvar lichen sclerosus (VLS) consists in reduction of inflammation, regeneration of tissues, volume increase, and pain fiber control. The main outcome of this study was the evaluation of patients' satisfaction after treatment. Secondary outcomes included modifications in symptoms, psychosexual wellbeing, vulvar hydration, and histology after surgery. METHODS: Eligible for this study were women aged 18-85 years with a histological diagnosis of VLS who underwent at least one autologous vulvar fat grafting at the authors' center, between 2010 and 2019. In 2021, all women underwent a clinical reevaluation, comprehensive of vulvoscopy, vulvar biopsy, and handing out of validated questionnaires. RESULTS: Overall, 88.7% of patients declared themselves very satisfied/satisfied with the procedure. All symptoms were improved postsurgery; in particular, the difference was statistically significant for pruritus, burning, and dyspareunia ( p < .05). Sexual function was also improved at time of reevaluation, as were depressive and anxiety symptoms ( p < .05). No cases of vulvar intraepithelial neoplasia or cancer occurred during follow-up and vulvar architecture remained stable, although patients reported a significantly reduced need for topical steroids ( p < .0001). Lastly, in postoperative biopsies, inflammatory infiltrate was stable or reduced, and the distribution of elastic fibers was comparable or restored in most patients. CONCLUSIONS: Patient satisfaction with fat grafting is detectable up to 11 years after surgery, and as such, it may represent a valid therapeutic option in selected cases of VLS.

Nonsclerotic Lichen Sclerosus: Definition of a Concept and Pathologic Description.

OBJECTIVE: Nonsclerotic lichen sclerosus (NSLS) refers to the clinicopathologic situation of examination findings consistent with lichen sclerosus (LS) but without dermal sclerosis on microscopy. This review aims to describe the features of NSLS and provide a classification framework. METHODS: The International Society of the Study of Vulvovaginal Diseases tasked the Difficult Pathologic Diagnoses Committee with development of consensus documents for conditions with problematic histopathology. The Difficult Pathologic Diagnoses Committee reviewed the literature on NSLS and formulated descriptions and diagnostic criteria, then approved by the International Society of the Study of Vulvovaginal Diseases membership. RESULTS: Nonsclerotic LS may be categorized into 4 histopathologic subtypes: lichenoid dermatitis, hypertrophic lichenoid dermatitis, dermal fibrosis without acanthosis, and dermal fibrosis with acanthosis. Each has a pathologic differential diagnosis of 1 or more entities, so clinical correlation is required for final diagnosis of LS. There is no evidence to support a reliable association between absent sclerosis and clinical appearance, duration, or oncogenic potential of LS. CONCLUSIONS: Pathologists and clinicians should be familiar with the concept of NSLS and its implications for patient management. Use of the term "early LS" to indicate a lack of sclerosis in presumed LS should be abandoned. Clinical correlation is required to confirm LS from among the differential diagnoses.

Reflectance confocal microscopy as a non-invasive imaging tool in vulvar high-grade squamous intraepithelial lesions and lichen sclerosus: A descriptive morphological study in patients and healthy volunteers.

Incorrect and delayed diagnosis of vulvar high-grade squamous intraepithelial neoplasia (vHSIL) and lichen sclerosus (LS) increases malignant progression risks and negatively impacts prognosis and quality of life. There is a need to improve diagnosis and monitoring. Reflectance confocal microscopy is a non-invasive imaging tool that visualizes skin structures at cellular resolution. The objectives were to explore feasibility and patient acceptability of vulvar RCM imaging and to identify RCM characteristics that are discriminative for vulvar HSIL and LS. This was a prospective, cross-sectional, observational clinical trial in patients with vHSIL and LS compared to healthy volunteers. RCM images and vulvar tissue samples were obtained. Five (5) patients with vHSIL, 10 patients with LS and 10 healthy volunteers were enrolled. In total, 100 image series of vulvar skin were obtained, including lesional and nonlesional sites. The RCM technique was considered acceptable for application by patients and healthy controls. Healthy vulvar skin was characterized by a homogenous, normal honeycomb patterned epidermis and a clear epidermal-dermal junctions. Vulvar HSIL and LS displayed an atypical honeycomb pattern of the epidermis and lymphocytic influx with presence of melanophages. Distinct features specifically observed in LS included the presence of hyalinised vessels and sclerotic areas in the dermis. RCM is a non-invasive imaging technique that is feasible and clinically acceptable to apply on vulvar skin, both in patients with premalignant lesions and healthy controls. Recognition and validation of disease-specific characteristics could make reflectance confocal microscopy a clinical tool to non-invasively aid identification of vulvar premalignancies.

Urinary microbiome differences between lichen sclerosus induced and non-lichen sclerosus induced urethral stricture disease.

OBJECTIVE: To describe differences in the urinary microbiome of patients with pathologically confirmed lichen sclerosus (LS) urethral stricture disease (USD) vs non-lichen sclerosus (non-LS) USD pre- and post-operatively. METHODS: Patients were pre-operatively identified and prospectively followed, all underwent surgical repair and had tissue samples obtained to make a pathological diagnosis of LS. Pre- and post-operative urine samples were collected. Bacterial genomic DNA was extracted. Alpha and beta diversity measurements were calculated and compared. A zero-inflated negative binomial model was utilized to compare taxa abundances between disease status and surgery status. RESULTS: Urine samples were obtained from both cohorts, 69 samples in total: 36 samples were obtained pre-operatively and 33 samples were obtained post-operatively. Ten patients provided both a pre-operative and post-operative urine sample. Twenty-six patients had pathological evidence of LS and 33 patients did not. There was a statistically significant difference in alpha diversity between the pre-operative urine samples of patients with non-LS USD and LS USD, (p = 0.01). There was no significant difference in alpha diversity within post-operative urine samples between patients with non-LS USD and LS USD, (p = 0.1). A significant difference was observed in Weighed UniFrac distances with respect to disease and operative status, (p = 0.001 and 0.002). CONCLUSIONS: LS USD have significant alterations in diversity and differential abundance of urine microbiota compared to non-LS USD controls. These findings could be used to guide further investigations into the role of the urinary microbiome in LS USD pathogenesis, severity of presentation, and stricture recurrence.

Vulvar Lichen Sclerosus Clinical Severity Scales and Histopathologic Correlation: A Case Series.

ABSTRACT: Several vulvar lichen sclerosus (VLS) clinical severity scales have recently been proposed. In this prospective case series, we characterized histopathology in the context of clinical severity in 6 treatment-naïve postmenopausal patients with VLS. The Vulvar Quality of Life Index (VQLI) and an adaptation of the 2018 International Society for the Study of Vulvovaginal Disease Delphi consensus VLS severity score were administered. Vulvar skin punch biopsies were obtained to measure inflammatory density, constituent inflammatory cells, thickness of the stratum corneum and other epidermal layers, dermal edema, and dermal sclerosis. Clinicopathologic correlations were assessed. Two cases demonstrated sparse inflammatory densities, 1 case demonstrated patchy and nodular inflammatory density, 1 case demonstrated dense lichenoid inflammatory density, and 2 cases demonstrated dense lichenoid and epitheliotropic inflammatory densities. Those patients who reported severe pruritus demonstrated the greatest lymphocytic inflammatory densities on histopathological examination. Both cases of ulceration or erosion were associated with severe VQLI scores. Severe VQLI scores were also associated with trends for higher average thickness of the epidermal layers and of dermal sclerosis. Altogether, histopathologic grading of biopsy sites may reflect clinical severity in patients with VLS.