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 evaluate a set of Ras oncogenic substitution changes at G12, G13 and Q61. We find that these variants fall into distinct groups based on phenotypic differences, sensitivity to gene dose 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 demonstrate oncogenic C. elegans Ras variants exhibit clear distinctions in how they interface with the vulva development network, and show that extracellular modulators yield variant-restricted effects in vivo.

Modified clock mapping biopsy sec. Della Corte-Bifulco in the preoperative assessment of excisional surgery for vulvar Paget's disease.

We have developed a biopsy technique aimed at preoperative evaluating the extent of Paget's vulvar disease in order to plan subsequent radical vulvar surgery. The aim is to find all possible lesion sites that are not visible macroscopically, to obtain a clear evaluation of the disease spread and to tailor the radical surgical procedure to remove even microscopic lesions, avoiding recurrences and excessively destructive surgery, adopting as conservative an approach as possible. We used this procedure for the first time to establish the radicality of the surgical intervention in a 68-year-old patient initially suffering from a single invasive vulvar Paget's lesion.

Unveiling the Truth: Fibroepithelial Polyp of the Vulva and Its Misdiagnosis as Cancer.

Fibroepithelial polyps (FEPs) are peculiar benign lesions that typically present as painless, pedunculated growths in various regions of the body, including the lower female genital tract. We discuss a case of a 45-year-old menopausal female who presented with an FEP in her vulva. The patient reported noticing a painless growth in her vulvar region for the past seven years, which had gradually increased in size. Clinical examination revealed a polypoidal, pedunculated, fleshy mass measuring approximately 11x8x7 cm in diameter. The lesion was excised under anesthesia, and histopathological examination confirmed the diagnosis of FEP. The patient had an uneventful postoperative course and showed no evidence of recurrence.

Genital calcinosis cutis: Microscopic evidence supporting a dystrophic origin.

Calcinosis cutis (CC) is characterized by the deposition of calcium salts in the skin and subcutaneous tissues. CC involving the vulva or foreskin (prepuce) is uncommon. We present a 9-year-old female with vulvar CC and a 15-year-old male with preputial CC. Microscopic review of excisional specimens revealed calcification associated with follicular cysts in the vulvar case and lichen sclerosus in the preputial case, suggesting a dystrophic origin to a subset of cases of genital CC that might otherwise be classified as idiopathic. The clinical implication of these findings is the need for close histopathologic scrutiny and ongoing clinical surveillance of patients with genital CC initially deemed idiopathic.

A Pigmented Lesion of the Vulva Revealing Aggressive Melanoma: A Case Report.

Vulvar melanoma (VM) is a rare and aggressive malignancy presenting unique challenges in diagnosis and management. This report presents the case of a 61-year-old female patient and explores the clinical characteristics, diagnostic modalities, treatment strategies, and prognosis associated with VM. The patient presented with a painless mass on the labia majora, which turned out to be an undifferentiated malignant tumor process consistent with melanoma on examination. Immunohistochemical analysis confirmed the diagnosis and subsequent imaging revealed metastatic disease necessitating palliative chemotherapy following radiotherapy. VM is a rare and aggressive form of melanoma. While surgery is the standard of care for early stages, advanced stages require a combination of immunotherapy and targeted treatments. Clinical trials are vital to improve our understanding of this condition and the various aspects of its care. Collaboration among experts is essential to achieve progress in managing these patients.

Prognostic characteristics, recurrence patterns, and survival outcomes of vulval squamous cell carcinoma - A twelve-year retrospective analysis of a tertiary centre.

INTRODUCTION: Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of vulval squamous cell carcinoma (SCC). METHODS: This is a retrospective cohort study of women who received treatment at Oxford University Hospitals between February 2010 and July 2022 for primary vulval SCC. RESULTS: We included 98 cases. The median age at diagnosis was 68 years. Human Papillomavirus (HPV) infection and lichen sclerosis were observed in 21 and 50 cases, respectively. Surgical excision was the primary treatment. Recurrence within 2 years was more common with advanced stage (p = 0.047, RR = 2.26) and extracapsular lymph node spread (p = 0.013, RR = 2.88). Local recurrence was not associated with a specific cut-off value for tumour-free margin. Poor survival outcomes were observed with higher grade (p = 0.01), advanced FIGO stage (p < 0.001), HPV-independent cancer (p = 0.048), lymph node involvement (p < 0.001, HR = 7.14), extracapsular spread (p < 0.001, HR = 7.93), lymphovascular space invasion (p = 0.002, HR = 3.17), tumour diameter wider than 23 mm (p = 0.029, HR = 2.53) and depth of invasion more than 6 mm (p = 0.006, HR = 3.62). Perineural invasion is associated with shorter disease-free survival. Five-year cancer-specific survival rates for stages I, III, and IV were 90.2%, 40.8%, and 14.3%, respectively.

Varied Clinical Presentations of Aggressive Angiomyxoma of the Vulva: A Rare Entity.

Objective: Aggressive Angiomyxoma (AA) of the vulva is a slow-growing mesenchymal tumour with a tendency to local invasion and recurrence. Case report: We report two cases of vulvoperineal masses that were diagnosed to be Aggressive Angiomyxomas after surgical excision. Both patients presented to the Gynaecology OPD of All India Institute of Medical Sciences, Bathinda, Punjab, India, in 2020 and 2022 with complaints of a mass coming out of introitus of three years duration and 14 years duration, respectively. The first patient was managed by surgical excision of the mass via abdominoperineal approach, while the second patient underwent vaginal hysterectomy along with the removal of the mass. Both patients were given GnRH analogues after the surgery to avoid any further recurrences and have been in remission on follow-ups so far. Conclusion: Due to its rare occurrence, clinicians should consider the possibility of AA while encountering patients with vulvovaginal masses to avoid misdiagnosis and delayed management.

Técnica Boomerang para plástica genital estética feminina / Boomerang technique for female genital aesthetic surgery

Introdução: A hipertrofia de pequenos lábios combinada com capuz clitoriano redundante é uma queixa comum entre mulheres que procuram cirurgia plástica genital cosmética por queixas funcionais, psicológicas e estéticas. O objetivo deste estudo foi descrever a técnica boomerang, um tratamento cirúrgico da hipertrofia labial que se estende a todo o capuz clitoriano. Método: Foi conduzido um estudo retrospectivo, de caráter analítico, para avaliar os prontuários médicos de 48 pacientes consecutivas submetidas a cirurgia estética genital feminina entre julho de 2017 e julho de 2021. Todos os procedimentos cirúrgicos foram realizados pela mesma cirurgiã. A técnica utilizada nas pacientes consistiu na ressecção longitudinal dos excessos de pequenos lábios vaginais associado à ressecção de capô clitoriano em forma de boomerang e à clitoropexia. Resultados: A idade média das pacientes submetidas a cirurgia foi de 36,25 anos (intervalo 18-59 anos), entre as quais 94,44% apresentaram queixas estéticas associadas ou não a queixas funcionais, e 5,56% apresentaram somente queixas funcionais. Duas pacientes apresentaram hematomas nos grandes lábios no pós-operatório imediato, e uma paciente teve deiscência de sutura nos pequenos lábios. Conclusão: A técnica boomerang é reprodutível e proporciona benefícios estéticos e/ou funcionais na genitália feminina.

Introduction: Hypertrophy of the labia minora combined with a redundant clitoral hood is a common complaint among women seeking aesthetic genital cosmetic surgery for functional, psychological, and aesthetic complaints. The objective of this study was to describe the boomerang technique, a surgical treatment for labial hypertrophy that extends to the entire clitoral hood. Method: A retrospective, analytical study was conducted to evaluate the medical records of forty-eight consecutive patients who underwent female genital cosmetic surgery between July 2017 and July 2021. The same surgeon performed all surgical procedures. The technique used in the patients consisted of longitudinal resection of excess small vaginal lips associated with resection of the boomerang-shaped clitoral hood associated with clitoroplasty. Results: The average age of patients undergoing surgery was 36.25 years (range 18-59 years), among whom 94.44% had aesthetic complaints associated or not with functional complaints, and 5.56% had only functional complaints. Two patients had bruises on the labia majora in the immediate postoperative period, and one patient had suture dehiscence on the labia minora. Conclusion: The boomerang technique is reproducible and provides aesthetic and/or functional benefits to the female genitalia.

Management of inguinal lymph nodes in locally advanced, surgically unresectable, squamous cell carcinoma of the vulva.

OBJECTIVE: To assess clinical outcomes of inguinal lymph node surgical resection compared to primary groin radiotherapy for locally advanced, surgically unresectable vulvar cancer. METHODS: All patients treated with radiation for vulvar cancer were identified between Jan 1, 2000 - Dec 31, 2020 at 2 academic centres. Inclusion criteria were those treated with curative intent primary radiotherapy +/- chemotherapy, tumors >4 cm, and surgically unresectable squamous cell vulvar carcinoma. Groin recurrence-free survival (RFS) was compared for groin surgery and primary groin radiotherapy using the Kaplan Meier method and log rank test. Groin failures are described by treatment modality, radiation dose and lymph node size. RESULTS: Of 476 patients treated with radiation for vulvar cancer, 112 patients (23.5%) met inclusion and exclusion criteria. The median (95% CI) follow up was 1.9 (1.4-2.5) years. Complete clinical response was significantly higher (80.0%) in patients with surgical groin resection compared to patients treated with primary groin radiotherapy (58.2%) (p = 0.04). On multivariable analysis, after adjusting for clinical and/or radiologically abnormal lymph nodes (p = 0.67), surgical groin resection was significantly associated with lower groin recurrence (HR 0.2 (95%CI 0.05-0.92), p = 0.04). The 3-year groin recurrence-free survival (RFS) was significantly higher at 94.4% (87.1-100) in patients with surgical groin resection compared to 79.2% (69.1-90.9) in patients treated with primary radiation (p = 0.02). CONCLUSIONS: In locally advanced squamous cell vulvar cancer, surgical groin management improves groin RFS compared to radiotherapy alone.

Insights into the vulvar component of the genitourinary syndrome of menopause (GSM).

Genitourinary syndrome of menopause is a comprehensive term that groups genital, urinary and sexual signs and symptoms mainly due sex hormone deficiency and aging, with a crucial impact on quality of life of midlife women. While this broad definition captures the common underlying physiopathology and the frequent overlap of symptomatology, improving knowledge about different components of genitourinary syndrome of menopause may be relevant for individualized treatment, with possible implications for efficacy, compliance and satisfaction. This narrative review focuses on the vulvar component of genitourinary syndrome of menopause, highlighting anatomical and functional peculiarities of the vulva that are responsible for some of the self-reported symptoms, as well as specific signs at physical examination. Increasing evidence points towards a pivotal role of vulvar vestibular health in the occurrence of sexual pain, one of the most common and distressing symptoms of genitourinary syndrome of menopause, which should be evaluated with validated scales taking a biopsychosocial perspective. This is an essential step in the recognition of different phenotypes of genitourinary syndrome of menopause and in the assessment of the most effective diagnostic and therapeutic algorithm. Menopausal vulvar health deserves more research into tailored non-hormonal and hormonal treatment options.

Anatomy of the clitoris: the corona of the glans clitoris, clitoral coronal papillae, and the coronopreputial frenulum.

The corona of the glans clitoris is a clinically important yet poorly understood anatomical structure. There has been longstanding confusion regarding the prevalence of the corona of the glans clitoris and, moreover, its very existence. Therefore, this anatomical study assesses the prevalence of the corona of the glans clitoris and the gross anatomy of the proximal glans clitoris. Anatomy was assessed in 104 female donor bodies ranging in age from 50 to 102 years with an average age-at-death of 78.1±10.9 years (mean±SD). All clitorises (100%; 104:104 dorsums and 100%; 208:208 sides) were found to have a well-defined clitoral corona. Three of 104 (2.9%) coronas possessed grossly visible, outward-projecting, bluntly rounded papillae. Some donors possessed a coronopreputial frenulum. Clitoropreputial adhesions were common and associated with clitoral pearls. Clitoral pearls were identified in 37.8% (14:37) of unembalmed donors and observed to create clitoral craters, structural deformations in the surface of the corona and glans. The results of this study suggest that the corona of the glans clitoris is a ubiquitous anatomical structure. The clitoral coronal papillae and coronopreputial frenulum are novel, previously undescribed, anatomical structures. This study identifies that the corona of the glans clitoris is prone to pathological processes such as clitoral pearl formation and clitoral deformation. In addition to novel anatomical findings, the results of this study call attention to the need for life-long clitoral examinations. Furthermore, the corona of the glans clitoris should be regularly included in anatomical texts and accurately depicted in anatomical illustrations.

Accurate detection of copy number aberrations in FFPE samples using the mFAST-SeqS approach.

BACKGROUND: Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS and challenges of small biopsies ask for an alternative to the untargeted NGS approaches. The mFAST-SeqS approach, relying on LINE-1 repeat amplification, showed a good correlation with Shallow-seq to detect CNA in blood samples. In the present study, we evaluated whether mFAST-SeqS is suitable to assess CNA in small formalin-fixed paraffin-embedded (FFPE) tissue specimens, using vulva and anal HPV-related lesions. METHODS: Seventy-two FFPE samples, including 36 control samples (19 vulva;17 anal) for threshold setting and 36 samples (24 vulva; 12 anal) for clinical evaluation, were analyzed by mFAST-SeqS. CNA in vulva and anal lesions were determined by calculating genome-wide and chromosome arm-specific z-scores in comparison with the respective control samples. Sixteen samples were also analyzed with the conventional Shallow-seq approach. RESULTS: Genome-wide z-scores increased with the severity of disease, with highest values being found in cancers. In vulva samples median and inter quartile ranges [IQR] were 1[0-2] in normal tissues (n = 4), 3[1-7] in premalignant lesions (n = 9) and 21[13-48] in cancers (n = 10). In anal samples, median [IQR] were 0[0-1] in normal tissues (n = 4), 14[6-38] in premalignant lesions (n = 4) and 18[9-31] in cancers (n = 4). At threshold 4, all controls were CNA negative, while 8/13 premalignant lesions and 12/14 cancers were CNA positive. CNA captured by mFAST-SeqS were mostly also found by Shallow-seq. CONCLUSION: mFAST-SeqS is easy to perform, requires less DNA and less sequencing reads reducing costs, thereby providing a good alternative for Shallow-seq to determine CNA in small FFPE samples.

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.

Adenocarcinoma of anogenital mammary gland type arising from encapsulated papillary carcinoma: A rare vulvar tumor mimicking breast carcinoma.

Anogenital mammary-like glands are normal structures of the anogenital region. Tumors originating from these glands often exhibit a striking resemblance to their mammary gland counterparts. Herein, we present a rare case of adenocarcinoma of mammary gland type in the vulva of a 69-year-old female. Histopathologic examination revealed a complex lesion, which included a large encapsulated papillary carcinoma (EPC) with associated invasive carcinoma of mammary gland type and ductal carcinoma in situ (DCIS). The invasive component consisted mostly of invasive ductal carcinoma of no special type, with a notable focus of invasive mucinous carcinoma. p40 immunostain demonstrated a lack of myoepithelial cells in both the EPC and invasive carcinoma, but such cells expressed p40 around the ducts involved by DCIS. The main component of this lesion, EPC, was characterized by a papillary proliferation within a cystic space surrounded by a fibrous capsule without a myoepithelial layer. The histopathologic features of anogenital EPC closely resemble cutaneous hidradenoma papilliferum. Indeed, there have been a few reports in the literature describing cases where in situ and invasive carcinoma arose from a preexisting hidradenoma papilliferum. As tumors of anogenital mammary-like glands bear a closer resemblance to breast lesions than to skin tumors, we recommend that they be aligned with the classification of well-established breast lesions rather than cutaneous adnexal tumors.

Low-level laser therapy: an efficient supplement to treatments of vulvar Lichen sclerosus to improve quality of life.

BACKGROUND: Lichen sclerosus (LS) is a chronic, inflammatory disease of the genital and extra genital skin, causing pruritus, soreness, pain and dyspareunia. The aim of this study was to investigate whether Low Level Laser Therapy (LLLT) can improve the quality of life in women with Lichen sclerosus (LS) and insufficient topical treatment. METHODS: In a descriptive prospective observational study conducted between 02.01.2016 and 08.01.2018, we included 100 women with LS with insufficient topical treatment because of poor response of symptoms. All participants received ten LLLT treatments (808 nm and 500 mW) over a period of 8 weeks. The first four treatments were planned as two treatments per week. The remaining six treatments were planned as once a week. A Danish health-related quality of life tool (HRQoL test) monitored the effect. RESULTS: A total of 94 patients completed the study, median age of 62 [InterQuartile Range 53-69]. There was a statistically significant improvement in seven of the eight domains of the HRQoL test after ten LLLT. We found the results of DoloTest to be statistically significant in all of the groups except for smoking (p < 0.094). CONCLUSIONS: LLLT treatment can improve the quality of life in women with LS.

Lichen sclerosus is a chronic, inflammatory disease of the genital and extra genital skin, causing pruritus, soreness, pain and dyspareunia. This study aimed to investigate whether Low Level Laser Therapy can improve the quality of life in women with Lichen sclerosus and insufficient topical treatment. The study proposed a supplemental therapy to insufficient topical treatment in patients with Lichen sclerosus. This study indicated that Low Level Laser Therapy treatment can improve the quality of life in women with Lichen sclerosus.

MRI Texture Analysis of Inguinal Lymph Node Metastasis in Vulvar Cancer - Associations With Histopathology.

BACKGROUND/AIM: Texture analysis is a quantitative imaging technique that provides novel biomarkers beyond conventional image reading. This study aimed to investigate the correlation between texture parameters and histopathological features of lymph nodes in patients with vulvar cancer. PATIENTS AND METHODS: Overall, nine female patients (mean age 70.1±13.4 years, range=39-87 years) were included in the analysis. All patients had squamous cell carcinomas and underwent upfront surgery with inguinal lymph node resection. Immunohistochemical assessment was performed using several markers of the epithelial-mesenchymal transition. The presurgical magnetic resonance imaging (MRI) was analyzed with the MaZda package. RESULTS: In discrimination analysis, several parameters derived from T1-weighted images showed statistically significant differences between non-metastatic and metastatic lymph nodes. The highest statistical significance was reached by the texture feature "S(0,3)InvDfMom" (p=0.016). In correlation analysis, significant associations were found between MRI texture parameters derived from both T1-weighted and T2-weighted images and the investigated histopathological features. Notably, S(0,3)InvDfMom derived from T1-weighted images highly correlated with the Vimentin-score (r=0.908, p=0.001). CONCLUSION: Several associations between MRI texture analysis and immunohistochemical parameters were identified in metastasized lymph nodes of cases with vulvar cancer.