[Staged operations of acquired lymphangiectasia of the vulva: 10 cases clinical analysis].

Objective: To investigate the characteristics, diagnosis and therapeutic effect of acquired lymphangiectasia of the vulva (ALV). Methods: A retrospective analysis of clinicopathological and follow-up data was conducted on the patients treated in Capital Medical University Affiliated Beijing Shijitan Hospital due to female ALV from July 2009 to July 2023. The patients who completed the staged operations [partial labiectomy and reconstruction + thoracic ductplasty and (or) perineal lymphovenous anastomosis] were included in the study and followed up. The improvement of perineal swelling, blister range, fluid leakage volume and frequency were evaluated through outpatient visits by the symptom rating scale of ALV (hereinafter referred to as the symptom rating scale) before and after surgery. Results: A total of 48 patients were treated due to ALV from July 2009 to July 2023, of which 98% (47/48) were postoperative pelvic malignant tumors and 94% (45/48) had a history of radiotherapy. A total of 10 patients with ALV who completed the staged operations were included in this study. (1) Clinical characteristics and diagnosis: 10 patients had a median age of 60 years old (50, 63 years old ). The median duration from cervical cancer surgery and radiation therapy to vulvar swelling was 1.5 years (0.0, 2.0 years), and the median duration from vulvar swelling to blister formation and leakage was 0.0 years (0.0, 4.8 years). Seven patients (7/10) had a history of recurrent erysipelas; 7 patients (7/10) had the most severe symptom (widespread blisters, persistent fluid leakage, and large amount of fluid leakage); noncontrast magnetic resonance lymphography (NCMRL) showed edema signals in the perineal region of all the patients, and increase of agent in the perineal region was observed in lymphoscintigram (LS). (2) Surgical treatment and postoperative pathological examination: of the 10 ALV patients who completed staged surgical treatment, 6 cases (6/10) were diagnosed with thoracic duct outlet obstruction and underwent thoracic ductplasty and partial labiectomy and reconstruction. Perineal lymphovenous anastomosis and partial labiectomy and reconstruction were performed in 4 cases (4/10) without thoracic duct outlet obstruction. Postoperative routine pathological examination of 10 patients (10/10) showed dermal papilla lymphangiectasia. Immunohistochemical tests were performed on 5 patients, all of which were positive for D2-40 and negative for CD34. (3) Efficacy: 8 patients completed the postoperative follow-up, and the median follow-up time was 31.0 months (17.5, 78.3 months). The perineal swelling and the blister fluid leakage were all significantly improved after the staged operations. All indexes of the symptom rating scale, including the degree of perineal swelling, blister range, fluid leakage volume and frequency, were significantly improved in 8 follow-up patients, and 3 (3/8) of them were cured; the median symptom score decreased significantly from 11.0 before surgery to 3.0 after surgery (P<0.001). The incidence of erysipelas was significantly reduced from 7/10 before surgery to 2/8 after surgery (P=0.035). Conclusions: The main causes of female ALV are pelvic tumor surgery and radiotherapy. The clinical diagnosis is made from relevant medical history, clinical manifestations, LS and magnetic resonance imaging. The diagnosis is confirmed by histopathological findings. Pathological results show lymphangiectasia in the dermal papilla, and immunohistochemical staining show positive for D2-40 and negative for CD34. The effect of staged surgery on ALV is remarkable and even cured, and could effectively reduce the incidence of erysipelas.

Vulvovaginal Atrophy Following Treatment for Oncogynecologic Pathologies: Etiology, Epidemiology, Diagnosis, and Treatment Options.

Vulvovaginal atrophy, characterized by the thinning of vaginal mucosa typically resulting from reduced estrogen levels, is frequently exacerbated by oncogynecologic treatments such as chemotherapy, hormonal therapy, radiotherapy, or surgery. This condition significantly impacts the quality of life for cancer survivors, leading to persistent discomfort, heightened infection risk, and negative effects on sexual function and self-esteem. Despite being a relatively common complication, vulvovaginal atrophy is not always discussed before the start of treatment. Treatments typically mirror those used for natural menopause; however, efficacy and safety data specific to this population are limited due to the exclusion of these patients from clinical trials. A major safety concern is the risk of hormone-sensitive cancer recurrence associated with estrogen therapy, which drives a preference for non-hormonal alternatives. Newer treatments, such as laser therapy, radiofrequency, and vaginal injections, show promise with minimal side effects and hormone-independent mechanisms, though efficacy data varies, highlighting the need for further research. This narrative review explores the epidemiology, risk factors, diagnosis, and management of vulvovaginal atrophy after the treatment for oncogynecologic disorders.

A Preliminary Study Using High-Frequency Ultrasound to Evaluate Vulvar Skin With Lichenoid Vulvar Dermatoses.

BACKGROUND: Lichenoid vulvar dermatoses (LVD) are inflammatory diseases primarily affecting the vulva and anus. This study aims to evaluate the skin changes in patients with LVD using high-frequency ultrasound. METHODS: Forty-five patients with LVD, who attended Henan Provincial People's Hospital from November 2021 to March 2024, were selected. According to the pathological conclusions, patients were divided into two groups: the vulvar lichen sclerosus (VLS) group (n = 24) and the vulvar lichen simplex chronicus (VLSC) group (n = 21). Thirty age- and BMI-matched healthy women were selected as the control group. We assessed the epidermal thickness, subepidermal low echogenic band (SLEB) thickness, dermal thickness, and vascular index (VI) among the three groups. Receiver operating characteristic curve (ROC) analysis was performed to determine the diagnostic efficacy of these ultrasound parameters for LVD. Binary logistic regression was used to investigate risk factors influencing LVD pathology in VLS patients. RESULTS: Epidermal thickness, SLEB thickness, dermal thickness, and VI were increased in the VLS and VLSC groups compared to the control group (p < 0.05). There were no statistically significant differences in ultrasound parameters between the VLS and VLSC groups (p > 0.05). The ROC curves showed that the area under the curve (AUC) value for the dermis (AUC = 0.882) was the largest for VLS, and VI (AUC = 0.917), it was the largest for VLSC. Binary logistic regression indicated that having an allergic disease was a risk factor for VLS between VLS and VLSC groups (OR = 6.797, p = 0.028). CONCLUSION: High-frequency ultrasound can detect thickening of the skin and increasing VI in patients with LVD, which can be helpful in the evaluation and management of LVD.

Persistent indurated plaques involving the forehead and vulva.

A 61-year-old female presented with progressive plaques on the left forehead and right labia.

A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans.

Oncogenic signaling through the MAPK/ERK pathway drives tumor progression in many cancers. Although targeted MAPK/ERK pathway inhibitors improve survival in selected patients, most tumors are resistant. New drugs could be identified in small-animal models that, unlike in vitro models, can address oral uptake, compound bioavailability, and toxicity. This requires pharmacologic conformity between human and model MAPK/ERK pathways and available phenotypic assays. In this study, we test if the conserved MAPK/ERK pathway in Caenorhabditis elegans could serve as a model for pharmacological inhibition and develop in vivo pipelines for high-throughput compound screens. Using fluorescence-based image analysis of vulva development as a readout for MAPK/ERK activity, we obtained excellent assay Z-scores for the MEK inhibitors trametinib (Z = 0.95), mirdametinib (Z = 0.93), and AZD8330 (Z = 0.87), as well as the ERK inhibitor temuterkib (Z = 0.86). The throughput was 800 wells per hour, with an average seed density of 25.5 animals per well. Readouts included drug efficacy, toxicity, and pathway specificity, which was tested against pathway activating upstream (lin-15)- and downstream (lin-1) mutants. To validate the model in a high-throughput setting, we screened a blinded library of 433 anticancer compounds and identified four MEK inhibitors among seven positive hits. Our results highlight a high degree of pharmacological conformity between C. elegans and human MAPK/ERK pathways, and the presented high-throughput pipeline may discover and characterize novel inhibitors in vivo. SIGNIFICANCE: Many tumors depend on MAPK/ERK signaling to sustain growth, avoid cell death, and metastasize. We show that specific and clinically relevant MAPK/ERK signaling inhibitors can be discovered in vivo with a high-throughput screening pipeline in small animals.

Ospemifene and vulvovaginal atrophy: an update of the clinical profile for post-menopausal women.

INTRODUCTION: The demand for effective and safe treatments of genitourinary syndrome (GSM) in post-menopausal women (PMW) is growing. Published data on the efficacy and safety of ospemifene (OSP) prompt an updated literature review to enlighten possible improvements in the GSM treatment. AREA COVERED: We searched articles published in English from 2010 to 2023 through Medline (PubMed) and Embase databases with Boolean terms: OSP, PMW, GSM, endometrium, breast cancer, cardiometabolic syndrome, bone metabolism, adherence to treatment, and patient satisfaction. We selected randomized controlled trials (RCTs) and observational and cross-sectional studies and completed the search manually. EXPERT OPINION: Of the 157 retrieved records, 25 primary studies met the inclusion criteria (15 regarding efficacy and safety, two for additional effects, and four for adherence and satisfaction with the OSP treatment). Seven RCTs involved nearly 5,000 patients, 10 out of 18 prospective observational studies 563, and six retrospective analyses 356,439. Evidence of OSP treatment in PMW with GSM relies on RCTs and remarkable real-world data. The 25 primary studies showcased the high clinical response to symptoms, the favorable safety profile of OSP with very few adverse events, a neutral impact on the endometrium, breast, bone, and thrombosis, and the possible improvement of cardiovascular risk factors.

Should I stay for local hormone therapy or should I go for radiofrequency to treat vulvovaginal atrophy? A patient preference trial.

OBJECTIVE: To compare patient satisfaction rate in postmenopausal women who chose dynamic quadripolar radiofrequency or topical estrogens as their preferred treatment for genitourinary syndrome of menopause. METHODS: Patients were divided into two groups according to their preference: one was treated with estrogen therapy (ET) and the other with dynamic quadripolar radiofrequency treatment (RF). All patients included fulfilled a series of validated questionnaires, at baseline and at the 6-mo follow-up, in order to evaluate the discomfort degree associated with the presence of vulvovaginal atrophy and the impact of the reported symptoms on QoL and sexuality. RESULTS: After propensity score matching, the proportion of women considering themselves satisfied with their genital health conditions was extremely small at study entry (5.2% of the RF group and 6.9% of the ET group), while at a 6-mo follow-up, it increased to 46.7% and 46.6%, respectively. No statistically significant between-group differences were found regarding mean numerical rating scale scores for dryness and dyspareunia at follow-up (5.6 ± 2.6 vs 5.3 ± 2.3, P = 0.5; and 2.9 ± 2.5 vs 3.0 ± 2.7, P = 0.46). At 6-mo follow-up, we observed no statistically significant differences between the two groups regarding the other items evaluated. RF treatment was overall well tolerated. CONCLUSION: The use of quadripolar radiofrequency devices seems effective, but it is not associated with better clinical outcomes compared with topical hormone treatment, which is a substantially cheaper and more convenient treatment for genitourinary syndrome of menopause. Therefore, we suggest limiting the use of dynamic quadripolar radiofrequency selectively when topical estrogens are not effective, not tolerated, or contraindicated.

Functional distinction in oncogenic Ras variant activity in Caenorhabditis elegans.

Ras genes are important oncogenes that are frequently mutated in cancer. Human oncogenic variants exhibit functional distinctions in terms of their representation in different cancer types, impact on cellular targets and sensitivity to pharmacological treatments. However, how these distinct variants influence and respond to the cellular networks in which they are embedded is poorly understood. To identify novel participants in the complex interplay between Ras genotype and cell interaction networks in vivo, we have developed and tested an experimental framework using a simple vulva-development assay in the nematode C. elegans. Using this system, we evaluated a set of Ras oncogenic substitution changes at G12, G13 and Q61. We found that these variants fall into distinct groups based on phenotypic differences, sensitivity to gene dosage and inhibition of the downstream kinase MEK and their response to genetic modulators that influence Ras activity in a non-autonomous manner. Together, our results demonstrated that oncogenic C. elegans Ras variants exhibit clear distinctions in how they interface with the vulva-development network and showed that extracellular modulators yield variant-restricted effects in vivo.

Extramammary breast cancer of the vulva.

A woman in her 70s was seen in the gynaecology outpatient clinic with a swelling on the right side of the vulva. Surgical excision of the lesion revealed unexpectedly an extensive ductal carcinoma in situ with a focus of a grade 2 invasive ductal carcinoma arising in extramammary breast tissue of the vulva. Postoperative staging studies showed normal breasts, with no evidence of disease elsewhere. The patient underwent a wider excision of the right vulva and sentinel node biopsy of the right inguinal region, which revealed no further disease. The patient is currently taking adjuvant hormonal therapy and has remained disease free at 2-year follow-up. This case underscores the importance of considering rare presentations of vulvar malignancies and the necessity for a multidisciplinary approach in managing such cases.

Understanding the Benefits of CO2 Laser Treatment for Vulvovaginal Atrophy.

Background and Objectives: Postmenopausal vaginal discomfort is often attributed to vulvovaginal atrophy (VVA). Women with VVA experience symptoms such as vaginal dryness, itching, burning, irritation, and dyspareunia. Materials and Methods: This pilot study was conducted to assess the effects of a micro-ablative fractional CO2 laser on the clinical symptoms of VVA, as well as concordant sexual function. The severity of VVA symptoms was evaluated by a visual analogue scale (VAS), while the condition of the vaginal mucosa was evaluated using the Vaginal Health Index Score (VHSI). Sexual function was evaluated using the Female Sexual Function Index (FSFI) Questionnaire. Results: Our cohort included 84 sexually active postmenopausal women with bothersome VVA, leading to sexual health complaints. The mean age of the participants in our study was 55.2 ± 5.4 years, with an average postmenopausal period of 6 ± 4.8 years. The age of our patients and the length of their postmenopausal period exhibited a significant negative correlation with VHSI scores, while a longer postmenopausal period was associated with increased severity of vaginal dryness and dyspareunia. Baseline VHSI values showed that 65% of patients had atrophic vaginitis with pronounced VVA symptoms (70.2% experienced vaginal itching, 73.8% reported vaginal burning, 95.3% had vaginal dryness, and 86.1% suffered from dyspareunia). Lower VHSI values significantly correlated with lower FSFI scores, while more severe VVA symptoms scores correlated with lower FSFI scores. VVA symptoms were significantly less severe after treatment. VHIS regained high non-atrophic values in 98.8% of patients post-treatment (p < 0.001). FSFI total and domain scores were significantly higher after treatment (p < 0.001). Conclusions: Our study revealed that fractional CO2 laser is a useful treatment option to alleviate VVA symptoms and improve vaginal health and sexual functioning in postmenopausal women.

A case of giant labia majora lipoma in an adult.

Lipomas are common benign adipose tissue tumors but are infrequently found in the labia majora, especially at a large size. We report a case of a giant lipoma of the labia majora in a 37-year-old woman diagnosed by imaging methods and successfully treated by surgery. This case highlights the importance of considering lipoma in the differential diagnosis of labial masses and underscores the role of imaging in diagnosis. They need to be differentiated from liposarcoma or omental herniation into Nuck's canal. It also demonstrates the effectiveness of surgical management for large lipomas in sensitive areas, with attention to both medical and aesthetic outcomes.

The effects of various therapies on vulvovaginal atrophy and quality of life in gynecological cancer patients: a systematic review.

PURPOSE: Tumors affecting the female genital tract and their treatments have the potential to induce adverse modifications in vaginal health and impact personal aspects of patient's lives. Vulvovaginal atrophy is one of the morphological changes observed in individuals with a history of gynecological cancer, influenced both by the biological environment of tumors and the main therapeutic modalities employed. Therefore, the purpose of this study was to identify approaches to treat vulvovaginal atrophy while assessing the impact on the emotional and sexual health of women diagnosed with gynecological cancers. METHODS: To achieve this goal, a systematic review was conducted following the methodological guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The databases used for literature research were PubMed and Web of Science. RESULTS: Initially, 886 articles were obtained. After eliminating duplicates and applying inclusion/exclusion criteria, seven articles were selected for analysis. The period of highest publication activity spanned from 2017 to 2020, with the majority conducted in Italy. Five treatment modalities were identified and categorized as vaginal suppository, oral medication, surgical procedure, CO2 laser therapy, and vaginal dilator. Twenty-four outcomes related to vaginal health and 30 outcomes related to overall, sexual, and emotional quality of life were analyzed. CONCLUSION: In general, all interventions demonstrated the ability to improve vaginal health or, at the very least, the sexual health of patients. Thus, despite limitations, all treatments have the potential to address vulvovaginal atrophy in patients with a history of gynecological cancer.

Tumour necrosis is a valuable histopathological prognostic parameter in melanomas of the vulva and vagina.

Vulvar and vaginal melanomas (VVMs) are rare and aggressive malignancies with limited prognostic models available and there is no standard reporting protocol. VVMs were selected from six tertiary Canadian hospitals from 2000-2021, resected from patients aged ≥18 years, with 6 months or longer follow-up data, and confirmation of melanocytic differentiation by at least two immunohistochemical markers. Cases were reviewed by pathologists to identify histological biomarkers. Survival outcomes were tested with Kaplan-Meier log-rank, univariate Cox, and multivariate Cox regression. There were 79 VVMs with median follow-up at 26 months. Univariate analysis revealed that tumour necrosis, tumour ulceration, positive lymph nodes, and metastasis at diagnosis were significantly associated with disease-specific mortality, progression, and metastasis. Multivariate analysis identified tumour necrosis as an independent prognostic factor for disease-specific mortality (HR 4.803, 95% CI 1.954-11.803, p<0.001), progression (HR 2.676, 95% CI 1.403-5.102, p=0.003), and time-to-metastasis for non-metastatic patients at diagnosis (HR 3.761, 95%CI 1.678-8.431, p=0.001). Kaplan-Meier survival analyses demonstrated that tumour necrosis was a poor prognostic factor for disease-specific, progression-free, and metastasis-free survival (p<0.001 for all comparisons). Vaginal melanomas displayed decreased survival compared to vulvar or clitoral melanomas. This study identifies tumour necrosis as an independent prognostic factor for VVMs. Vaginal melanomas specifically showed worse survival outcomes compared to vulvar or clitoral melanomas, consistent with previously reported findings in the literature, emphasising the importance of differentiating between these primary tumour epicentres for prognostication and treatment planning in the care of genital melanoma patients.

Nodular Vulvar Lesions.

A woman in her 30s presented with mildly itchy skin nodules in the vulvar region for 1 year, which occurred during pregnancy and increased gradually in size and number without any treatments. What is your diagnosis?

Histopathologic patterns of female genital tuberculosis with clinical correlation: a 10-year (2013-2022) retrospective cross-sectional study.

OBJECTIVE: Underdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status. METHODS: A retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022. RESULTS: Female genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix. CONCLUSION: Female genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity.

Labia minora hypertrophy: pathologizing diversity?

INTRODUCTION: Labia minora hypertrophy can be characterized by the labial tissue extending beyond the labia majora; however, the exact definition of hypertrophy is a matter of debate. While the prevalence of labia hypertrophy is very common among women, taboo/controversial attitudes and surgical interventions still dominate. The recognition and study of labia minora hypertrophy will increase our knowledge of this underrepresented anatomic diversity. OBJECTIVES: To provide a report of the current literature on labia hypertrophy and discuss the definition, etiology, attitudes, management, and medicalization surrounding labia minora hypertrophy and the implications. METHODS: Comprehensive review of literature pertaining to labia minora hypertrophy. RESULTS: Labia minora appearance and measurements vary extensively, and hypertrophy is extremely prevalent in the population and largely nonpathologic. There remains a lack of standardized criteria to define labia hypertrophy. Attitudes surrounding labia hypertrophy differ globally, but in Western nations the overwhelming sentiment toward labia hypertrophy has largely been medicalized. CONCLUSION: Negative attitudes and unnecessary medicalization of nonpathologic instances of labia hypertrophy is unjustifiable and comes with potential risks. There remains an impending need to demedicalize nonpathologic elongated labia, educate the public on diverse genital appearance, and improve understanding of the long-term outcomes and risks of genital cosmetic surgery.

Fibroadenoma of the vulva with pseudoangiomatous stromal hyperplasia: A common neoplasm in uncommon site.

Mammary-type tissue in the vulva was first described in 1872 but has been rarely reported in the literature. This tissue was previously considered as ectopic breast tissue that occurs as a result of incomplete regression of the milk line. Similar to native breast tissue, ectopic mammary tissue is hormone-sensitive and can develop benign changes, such as fibroadenoma, as well as malignant changes. A more recent theory suggests that these benign and malignant mammary-type entities arise from mammary-like anogenital glands, which constitute normal vulvar components. We report a case of a 41-year-old woman who presented with a chronic asymptomatic cyst on the left vulva that eventually became uncomfortable, especially on standing. The cyst was located on the labium minus, measuring 1.0 × 0.5 cm, with no identified erythema or other skin abnormalities. Excision of the lesion and subsequent microscopic examination showed a circumscribed mass with a nodular overgrowth of epithelial and stromal components, resembling a mammary fibroadenoma with pseudoangiomatous stromal hyperplasia. We bring to attention this rare diagnosis and the importance of considering it in the presence of a vulvar lesion. The malignant and recurrence potential of mammary-type tissue necessitates excision with clear margins and close monitoring of these patients.

Vulvovaginal atrophy in women with and without a history of breast cancer: Baseline data from the PatiEnt satisfactiON studY (PEONY) in Italy.

OBJECTIVES: To assess clinical characteristics of postmenopausal women with moderate/severe vulvovaginal atrophy, as well as its impact on sexual function, well-being, and quality of life, and to provide an overview of most used treatments. STUDY DESIGN: Ongoing longitudinal, observational study conducted in 17 Italian gynecology centers, involving women already treated or initiating a local vaginal estrogen therapy or ospemifene. We report baseline data for women with and without a history of breast cancer. Participants filled in self-reported questionnaires at study entry. MAIN OUTCOME MEASURES: Severity of vulvovaginal atrophy; ongoing treatments; patient-reported outcomes, including severity of symptoms, Day-to-Day Impact of Vaginal Aging (DIVA), Female Sexual Function Index (FSFI), Female Sexual Distress Scale-Revised (FSDS-R), and SF-12® Health Survey. RESULTS: Overall, 334 women (20.4 % with a history of breast cancer) started or continued local therapy (61.1 %) or ospemifene (38.8 %) at study entry. Vulvovaginal atrophy was severe in 28.6 %, and was responsible for severe symptoms, particularly vulvar dryness with burning or irritation and pain during sexual intercourse. Both sexual dysfunction (FSFI≤26) (81.5 %) and sexual distress (FSDS-R ≥ 11) (74.4 %) were common. A reduction in the SF-12 mental component score was documented. Women with breast cancer more often had severe vulvovaginal atrophy (41.2 %), had more severe symptoms, and the impact of vaginal symptoms on emotional well-being, sexual functioning and self-concept/body image was greater. The majority of them (83.8 %) received ospemifene as a treatment. CONCLUSIONS: Moderate/severe vulvovaginal atrophy is a common, often neglected condition with an impact on QoL and sexuality, particularly in women with a history of breast cancer. It is important to alleviate the burden associated with the disease.