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9 pages, 1144 KB  
Article
Artificial Intelligence and Colposcopy: Detection and Classification of Vulvar HPV-Related Low-Grade and High-Grade Squamous Intraepithelial Lesions
by Miguel Mascarenhas, Vanitha Sivalingam, Inês Castro, Katie Jones, Miguel Martins, Inês Alencoão, Maria João Carinhas, Joana Mota, Pedro Cardoso, Francisco Mendes, Maria João Almeida, Bruno Mendes, João Ferreira, Guilherme Macedo, Teresa Mascarenhas, Ahsan Javed and Rosa Zulmira Macedo
J. Clin. Med. 2025, 14(19), 7065; https://doi.org/10.3390/jcm14197065 - 7 Oct 2025
Viewed by 204
Abstract
Background/Objectives: Accurate identification of vulvar high-grade squamous intraepithelial lesions (HSIL) is essential for preventing progression to invasive squamous cell carcinoma. This study addresses the gap in artificial intelligence (AI) applications for vulvar lesion diagnosis by developing and validating the first convolutional neural [...] Read more.
Background/Objectives: Accurate identification of vulvar high-grade squamous intraepithelial lesions (HSIL) is essential for preventing progression to invasive squamous cell carcinoma. This study addresses the gap in artificial intelligence (AI) applications for vulvar lesion diagnosis by developing and validating the first convolutional neural network (CNN) model to automatically detect and classify HPV-related vulvar lesions—specifically HSIL and low-grade squamous intraepithelial lesions (LSIL)—based on vulvoscopy images. Methods: This bicentric study included data from 28 vulvoscopies, comprising a total of 9857 annotated frames, categorized using histopathological reports (HSIL or LSIL). The dataset was divided into training, validation, and testing sets for development and assessment of a YOLOv11-based object detection model. Results: The CNN demonstrated a recall (sensitivity) of 99.7% and a precision (positive predictive value) of 99.1% for lesion detection and classification. Conclusions: This is the first AI model developed for detecting and classifying HPV-related vulvar lesions. The integration of such models into vulvoscopy could significantly improve diagnostic accuracy and positively impact women’s health by reducing the need for potentially invasive and anatomy-altering procedures. Full article
(This article belongs to the Section Oncology)
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15 pages, 655 KB  
Review
Viral Infections of the Vulva: A Narrative Review
by Matteo Terrinoni, Tullio Golia D’Augè, Ottavia D’Oria, Michele Palisciano, Federica Adinolfi, Dario Rossetti, Gian Carlo Di Renzo and Andrea Giannini
Life 2025, 15(9), 1365; https://doi.org/10.3390/life15091365 - 28 Aug 2025
Viewed by 1004
Abstract
Vulvar viral infections such as condyloma acuminata, genital herpes, molluscum contagiosum, and Lipschütz ulcers span both sexually and non-sexually transmitted diseases and affect patients across all age groups. Lesions may present as papules, verrucous growths, or painful ulcers, often causing functional impairment and [...] Read more.
Vulvar viral infections such as condyloma acuminata, genital herpes, molluscum contagiosum, and Lipschütz ulcers span both sexually and non-sexually transmitted diseases and affect patients across all age groups. Lesions may present as papules, verrucous growths, or painful ulcers, often causing functional impairment and significant psychosocial distress. A multidisciplinary strategy that integrates epidemiology, precise diagnostics, individualized therapy, and psychological support is essential to optimize outcomes. We performed a structured literature search in PubMed, Scopus, and Web of Science using terms “vulvar viral infection,” “HPV,” “HSV,” “molluscum contagiosum,” and “Lipschütz ulcers.” International guidelines from the UK, Europe, and Australia were reviewed, alongside reference lists of key articles. Particular attention was given to paradoxical presentations, pediatric considerations, and cost-effectiveness analyses. HPV vaccination programs have markedly reduced anogenital warts, while early PCR/NAAT for HSV accelerates targeted antiviral therapy. First-line treatments like oral acyclovir/famciclovir for HSV and topical imiquimod or podophyllotoxin (±cryotherapy) for HPV are supported by adjunctive measures for self-limiting conditions. Host factors (hormonal cycles, immune status) and local irritants modulate recurrence risk, informing anticipatory suppressive regimens and barrier-reinforcing care. Validated patient-reported outcome measures (VPAQ, DLQI, FSFI) capture pain, sexual function, and quality-of-life impacts. Health–economic evaluations underscore the long-term value of rapid diagnostics and broad vaccination. Personalized, multidisciplinary management that combines prevention, precision diagnostics, tailored therapy, psychosocial support, and economic considerations offers the greatest promise for improving clinical and quality-of-life outcomes in patients with vulvar viral infections. We aim to outline best practices for the diagnosis and management of common vulvar viral infections, providing practical guidance for clinicians to improve recognition and therapeutic decision-making. Full article
(This article belongs to the Section Medical Research)
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11 pages, 3384 KB  
Case Report
Late Recurrence of High-Grade Vulvar Leiomyosarcoma After 5 Years: A Rare Case Report and Expanded Review of Reported Cases
by Angel Yordanov, Ivan Ivanov, Stoyan Kostov, Ihsan Hasan and Vasilena Dimitrova
J. Clin. Med. 2025, 14(17), 6032; https://doi.org/10.3390/jcm14176032 - 26 Aug 2025
Viewed by 619
Abstract
Background: Vulvar leiomyosarcoma (VLMS) is a rare and aggressive soft tissue malignancy arising from smooth muscle cells, comprising less than 3% of vulvar cancers. Its clinical resemblance to benign vulvar lesions often leads to delayed diagnosis. Despite surgical resection and adjuvant therapy, VLMS [...] Read more.
Background: Vulvar leiomyosarcoma (VLMS) is a rare and aggressive soft tissue malignancy arising from smooth muscle cells, comprising less than 3% of vulvar cancers. Its clinical resemblance to benign vulvar lesions often leads to delayed diagnosis. Despite surgical resection and adjuvant therapy, VLMS is associated with high recurrence rates and a poor prognosis, and due to its rarity, there is no standardized management or surveillance protocol. Case Report: We present a case of high-grade VLMS in a postmenopausal woman, initially diagnosed in 2020 and managed with surgical excision and adjuvant radiotherapy. The primary tumor was a 10 cm solid, lobulated mass involving the mons pubis, with histology confirming high-grade leiomyosarcoma based on marked cellular atypia, high mitotic activity, and smooth muscle differentiation. Immunohistochemistry was positive for SMA, vimentin, and CD34, and negative for S100 and MyoD1. Five years later, the patient developed a local recurrence with an enlarged inguinal lymph node. She underwent complete tumor resection and bilateral inguinal lymphadenectomy. Histology of the recurrent lesion mirrored the initial findings, with no lymph node metastases. This case highlights the aggressive nature and potential for late recurrence in vulvar leiomyosarcoma, underscoring the importance of long-term surveillance. Conclusions: High-grade VLMS is a rare malignancy with a high recurrence risk. This case highlights the importance of early diagnosis, radical surgical treatment, and long-term surveillance. Although recurrence occurred five years after the initial treatment, timely surgical intervention led to a favorable postoperative course. Multidisciplinary management and individualized follow-up strategies remain key to improving outcomes in these rare gynecologic sarcomas. Full article
(This article belongs to the Section Oncology)
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12 pages, 2097 KB  
Case Report
The Clinical Management and Outcomes of Two Cases of Vulvar Neoplasms: A Two-Case Study of VIN 3 and Stage IA Vulvar Keratinizing Squamous Cell Carcinoma
by Oana Denisa Balalau, Fernanda Ecaterina Augustin, Cristian Balalau, Romina Marina Sima and Liana Ples
J. Mind Med. Sci. 2025, 12(2), 40; https://doi.org/10.3390/jmms12020040 - 29 Jul 2025
Viewed by 732
Abstract
Vulvar carcinoma is the fourth most common gynecological cancer, with squamous cell carcinoma being the most frequent type. Vulvar intraepithelial neoplasia (VIN) is a precursor lesion and is strongly associated with human papillomavirus (HPV) infection. This paper presents two patients in their sixth [...] Read more.
Vulvar carcinoma is the fourth most common gynecological cancer, with squamous cell carcinoma being the most frequent type. Vulvar intraepithelial neoplasia (VIN) is a precursor lesion and is strongly associated with human papillomavirus (HPV) infection. This paper presents two patients in their sixth decade of life, the first diagnosed with VIN 3 (carcinoma in situ) and the second with stage IA keratinizing squamous cell carcinoma. Both patients had HPV infection; immunohistochemistry confirmed HPV-dependent VIN3 in the first case, while the second patient had a pre-existing HPV high-risk 53 infection. Both patients underwent partial vulvectomy, with the second also having bilateral inguinal–femoral lymph node dissection, which showed no lymph node invasion. The first patient had a histopathological result of VIN 3 with clear margins. The second patient underwent adjuvant radiotherapy following restaging pathology. Both are showing favorable postoperative progress. Conclusions. The early diagnosis of vulvar neoplasms enables less radical but effective surgeries, balancing oncologic control with quality of life. A multidisciplinary approach is essential for adjusting treatments, improving both clinical outcomes and patient well-being. Full article
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52 pages, 3227 KB  
Review
Advances in Photodynamic Treatment of Precancerous and Cancerous Gynecological Diseases
by Polina Alekseeva, Vladimir Makarov, Kanamat Efendiev, Aida Gilyadova and Victor Loschenov
Cancers 2025, 17(15), 2421; https://doi.org/10.3390/cancers17152421 - 22 Jul 2025
Viewed by 1198
Abstract
High mortality rates and poor quality of life result from the late-stage detection and frequent recurrence of gynecological neoplasms. Background/Objectives: The aim of this study was to conduct a systematic analysis of the energy parameters of photodynamic therapy (PDT) in the treatment [...] Read more.
High mortality rates and poor quality of life result from the late-stage detection and frequent recurrence of gynecological neoplasms. Background/Objectives: The aim of this study was to conduct a systematic analysis of the energy parameters of photodynamic therapy (PDT) in the treatment of cervical and vulvar lesions, with a focus on stimulating immune responses leading to human papillomavirus (HPV) eradication and lesion regression without adverse effects, such as thermal damage. Methods: A total of 46 peer-reviewed studies published between January 2010 and April 2024 were analyzed. These studies focused on PDT applications for cervical and vulvar lesions, sourced from Google Scholar, Scopus, and Web of Science. Results: Although PDT shows promise, significant limitations exist, such as insufficient consideration of individual tumor characteristics, restricted treatment depths, and the heterogeneous distribution and low selectivity of photosensitizer (PS) accumulation in tumors. Tumor hypoxia further reduces PDT’s effectiveness, and most studies overlook immune system activation, which is crucial for targeting HPV infections and improving antitumor responses. Conclusions: Advancing the research into PDT’s molecular and cellular mechanisms, optimizing the immune response stimulation, and improving the PS and delivery methods could enhance the safety and effectiveness of cervical and vulvar neoplasm treatments. The use of personalized PDT parameters may reduce the side effects and enhance the outcomes for patients suffering from gynecological diseases. Full article
(This article belongs to the Special Issue New Advances in the Diagnosis of Gynecological Cancer)
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16 pages, 574 KB  
Review
Advances in Vulvar Cancer: A Radiation Oncology Perspective
by Diandra N. Ayala-Peacock and Manjeet Chadha
Cancers 2025, 17(15), 2415; https://doi.org/10.3390/cancers17152415 - 22 Jul 2025
Viewed by 1037
Abstract
Despite being a rare malignancy, there have been several changes in the management paradigm for vulvar cancer. This review of the literature was undertaken to highlight key areas of treatment innovation and progress, including efforts to de-escalate morbid surgical resection as well as [...] Read more.
Despite being a rare malignancy, there have been several changes in the management paradigm for vulvar cancer. This review of the literature was undertaken to highlight key areas of treatment innovation and progress, including efforts to de-escalate morbid surgical resection as well as perform dose escalation of radiotherapy and incorporation of modern systemic agents to achieve better oncologic outcomes. There is still much debate regarding key high-risk pathology features and their corresponding prognostic significance and indications for adjuvant treatments. However, we are also developing a more nuanced understanding of the importance of precursor lesions and resultant subtypes of vulvar cancer, which suggests that there are more subtypes beyond the umbrella distinction of HPV status. Moving forward, we anticipate there will be an increasing number of trials investigating the triaging of management recommendations based on risk. Full article
(This article belongs to the Special Issue Advances in Vulvar Cancer)
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17 pages, 1748 KB  
Review
Vulvar Hemangioma: A Review
by Wing-Yu Sharon Siu, Yen-Chang Chen and Dah-Ching Ding
Diagnostics 2025, 15(10), 1270; https://doi.org/10.3390/diagnostics15101270 - 16 May 2025
Cited by 1 | Viewed by 3110
Abstract
Objectives: To review the clinical presentation, diagnostic approach, treatment strategies, and outcomes of vulvar hemangiomas, and to evaluate the consistency of management practices in the absence of standardized guidelines. Eligibility criteria: We included case reports, case series, and observational studies describing [...] Read more.
Objectives: To review the clinical presentation, diagnostic approach, treatment strategies, and outcomes of vulvar hemangiomas, and to evaluate the consistency of management practices in the absence of standardized guidelines. Eligibility criteria: We included case reports, case series, and observational studies describing vulvar hemangiomas with clinical, histological, and management data in human subjects. Reviews, editorials, and studies unrelated to vulvar hemangiomas were excluded. Information sources: Systematic searches were conducted in PubMed, Embase, Scopus, and Web of Science up to 20 February 2025, with additional citation tracking. Results: 85 studies were included. Data were synthesized narratively due to heterogeneity in the study design and outcome reporting. Most studies described symptomatic lesions presenting as swelling, bleeding, or pain, often misdiagnosed as Bartholin cysts or varicosities. Treatment varied widely, including observation, surgical excision, embolization, and medical therapies. No evidence-based guidelines were identified. Conclusions: Vulvar hemangiomas are rare and frequently misdiagnosed. While asymptomatic lesions may be observed, symptomatic cases require individualized treatment. This review highlights the need for diagnostic vigilance and the development of standardized management protocols. Further research is needed to optimize clinical outcomes. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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16 pages, 15208 KB  
Review
Transperineal Vulvar Ultrasound: A Review of Normal and Abnormal Findings with a Proposed Standardized Methodology
by Nina Montik, Camilla Grelloni, Giovanni Delli Carpini, Jessica Petrucci, Jacopo Di Giuseppe and Andrea Ciavattini
Diagnostics 2025, 15(5), 627; https://doi.org/10.3390/diagnostics15050627 - 5 Mar 2025
Viewed by 6153
Abstract
The vulva is a complex anatomical organ that may present with a wide range of pathologies. Even if it can be easily investigated, correctly interpreting vulvar appearance is often challenging. Vulvar ultrasound is an emerging diagnostic technique that may be helpful in different [...] Read more.
The vulva is a complex anatomical organ that may present with a wide range of pathologies. Even if it can be easily investigated, correctly interpreting vulvar appearance is often challenging. Vulvar ultrasound is an emerging diagnostic technique that may be helpful in different aspects of vulvar pathology. We aimed to summarize the state of the art of vulvar ultrasound, provide the necessary theoretical bases of embryology and anatomy, describe the normal and pathological vulvar sonographic characteristics, and propose a feasible and reproducible methodology for vulvar ultrasound. Vulvar sonographic scan should be performed with a linear probe, preferably > 15 mHz, following a standardized methodology. The sonographic appearance of the normal vulva reflects the different histology of its structures and, thus, their embryogenetic origin. The description of a suspected vulvar lesion should include localization, dimensions, volume, type of growth, shape, appearance of the edges, depth of invasion, echogenicity, and identification of vascularization. Cystic dilatation of obstructed Bartolini ducts is the most common benign finding in the vulva (fluctuant structures in the posterior third of the labia majora containing clear mucous fluid). Malignant vulvar lesions appear as hypoechogenic or heterogeneous solid lesions with irregular margins and a high degree of vascularization. Extramammary Paget Disease presents a homogeneous hypoechogenic creeping area in the epidermis due to neoplastic cells typical of this disease. The potential applications of vulvar ultrasound are examining the content of a vulvar swelling to guide its management and assessing the response to medical treatment in the case of lichen sclerosus. In managing patients affected by vulvar malignancies, it may play a critical role in local staging, stromal invasion determination, measuring the distance from the midline, and assessing the eligibility for sentinel lymph node procedure. Vulvar ultrasound is a minimally invasive and economical test that can be performed with minimal equipment. Further studies will be necessary to validate the clinical applications, quantify the diagnostic performance, and evaluate the agreement between operators. Full article
(This article belongs to the Special Issue Exploring Gynecological Pathology and Imaging)
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8 pages, 2273 KB  
Case Report
Vulvar Lymphangiectasia After Therapy for Cervical Cancer: A Case Report and Literature Review
by Vincenzo Pinto, Christopher Clark, Doriana Di Nanni, Amerigo Vitagliano, Grazia Pinto and Gerardo Cazzato
J. Clin. Med. 2025, 14(5), 1675; https://doi.org/10.3390/jcm14051675 - 1 Mar 2025
Viewed by 1655
Abstract
Background: Vulvar lymphangiectasia (VLA) is a rare condition characterized by the abnormal dilation of lymphatic vessels in the vulvar region, often secondary to surgery or radiation therapy for malignancies. Its clinical presentation closely resembles other dermatological conditions, posing challenges for accurate diagnosis [...] Read more.
Background: Vulvar lymphangiectasia (VLA) is a rare condition characterized by the abnormal dilation of lymphatic vessels in the vulvar region, often secondary to surgery or radiation therapy for malignancies. Its clinical presentation closely resembles other dermatological conditions, posing challenges for accurate diagnosis and appropriate management. This study aims to present a rare case of VLA occurring decades after cervical carcinoma surgery, contributing to the limited literature on this condition and offering insights into its differential diagnosis and management. Methods: A 70-year-old female patient presented with multiple fluid-filled vesicles in the vulvar region appearing 36 years after undergoing radical hysterectomy with pelvic lymphadenectomy for cervical carcinoma. The lesions were biopsied, and histopathological and immunohistochemical analyses were performed to confirm the diagnosis. A review of the existing literature on VLA was conducted to contextualize this case. Results: A histopathological examination revealed papillomatous lesions with hyper-keratosis, dilated lymphatic vessels, and no signs of atypia, consistent with VLA. An immunohistochemical analysis confirmed the lymphatic nature of the lesions. Due to the patient’s comorbidities, asymptomatic presentation, and lesion stability, conservative management with regular follow-up was chosen. No progression or complications were observed during the 12-month follow-up period. Conclusions: This case highlights the importance of considering VLA in patients presenting with vulvar vesicles, especially those with a history of lymphatic disruption. An accurate diagnosis through histopathological and immunohistochemical techniques is essential to distinguish VLA from other conditions. Conservative management may be appropriate for asymptomatic cases, but tailored therapeutic strategies are needed to address symptomatic or disfiguring lesions. Full article
(This article belongs to the Section Oncology)
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11 pages, 1588 KB  
Article
Circulating MicroRNAs in Patients with Vulvar Squamous Cell Carcinoma and Its Precursors
by Julia Rymuza, Angelika Długosz, Kamil Zalewski, Artur Kowalik, Mateusz Bujko and Magdalena Kowalewska
Non-Coding RNA 2025, 11(1), 13; https://doi.org/10.3390/ncrna11010013 - 7 Feb 2025
Viewed by 1162
Abstract
Objectives: Vulvar squamous cell carcinoma (VSCC) is a rare gynecologic malignancy, with most cases arising from differentiated vulvar intraepithelial neoplasia (dVIN). Approximately one-third of VSCC cases originate from high-grade squamous intraepithelial lesions (HSILs), which are associated with persistent infection by varieties of [...] Read more.
Objectives: Vulvar squamous cell carcinoma (VSCC) is a rare gynecologic malignancy, with most cases arising from differentiated vulvar intraepithelial neoplasia (dVIN). Approximately one-third of VSCC cases originate from high-grade squamous intraepithelial lesions (HSILs), which are associated with persistent infection by varieties of high-risk human papillomavirus (hrHPV). This study aimed to quantify the circulating microRNAs (miRNAs) in the plasma of patients with premalignant conditions (dVIN and HSILs) and VSCC using TaqMan Low-Density Arrays. Methods: Plasma samples were collected from 40 patients, including those treated for HSILs, dVIN, and VSCC. Quantitative real-time PCR (qRT-PCR) identified the circulating miRNAs differentially expressed in the plasma of VSCC patients compared to patients with precancerous lesions. Results: A total of 31 differentially expressed miRNAs (DEMs) were found to be significantly upregulated in plasma from VSCC patients compared to precancerous cases. None of the analyzed miRNAs were able to distinguish VSCC cases based on hrHPV tumor status. Conclusions: This study provides strong evidence that a distinct set of miRNAs can differentiate between plasma samples from VSCC patients and those with precancerous lesions. Thus, these DEMs have potential diagnostic and prognostic value. “Predisposing” DEMs could be developed as biomarkers to aid in the assessment of vulvar lesions, helping to exclude or confirm progression toward cancer. Full article
(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)
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11 pages, 497 KB  
Article
Role of Age, Comorbidity, and Frailty in the Prediction of Postoperative Complications After Surgery for Vulvar Cancer: A Retrospective Cohort Study with the Development of a Nomogram
by Giovanni Delli Carpini, Francesco Sopracordevole, Camilla Cicoli, Marco Bernardi, Lucia Giuliani, Mariasole Fichera, Nicolò Clemente, Anna Del Fabro, Jacopo Di Giuseppe, Luca Giannella, Enrico Busato and Andrea Ciavattini
Curr. Oncol. 2025, 32(1), 21; https://doi.org/10.3390/curroncol32010021 - 31 Dec 2024
Cited by 2 | Viewed by 1410
Abstract
Surgery is the cornerstone of vulvar cancer treatment, but it is associated with a significant risk of complications that may impact prognosis, particularly in older patients with multiple comorbidities. The objective of this study was to evaluate the role of age, comorbidities, and [...] Read more.
Surgery is the cornerstone of vulvar cancer treatment, but it is associated with a significant risk of complications that may impact prognosis, particularly in older patients with multiple comorbidities. The objective of this study was to evaluate the role of age, comorbidities, and frailty in predicting postoperative complications after vulvar cancer surgery and to develop a predictive nomogram. A retrospective cohort study was conducted, including patients who underwent surgery for vulvar cancer at two Italian institutions from January 2018 to December 2023. A logistic regression model for the rate of Clavien-Dindo 2+ 30-days complications was run, considering the age-adjusted Charlson Comorbidity Index (AACCI), body mass index (BMI), and frailty as exposures. Lesion characteristics and surgical procedures were considered as confounders. Among the 225 included patients, 50 (22.2%) had a grade 2+ complication. The predictive score of the nomogram ranged from 44 to 140. The AACCI (0–64 points) and BMI (0–100 points) were independently associated with a risk of complications. A nomogram including the AACCI and BMI predicts the risk of complications for patients undergoing surgery for vulvar cancer. The preoperative determination of the risk of complications enables surgical planning and allows a tailored peri- and postoperative management plan. Full article
(This article belongs to the Section Gynecologic Oncology)
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18 pages, 2023 KB  
Systematic Review
Vulvar Epidermolytic Hyperkeratosis: A Comprehensive Systematic Review of Case Reports and Series
by Miruna Ioana Cristescu, Elena Codruța Cozma, Cristina Beiu, Irina Tudose, Selda Ali, Anca Bobircă and Liliana Gabriela Popa
J. Clin. Med. 2025, 14(1), 94; https://doi.org/10.3390/jcm14010094 - 27 Dec 2024
Viewed by 2012
Abstract
Background: Vulvar epidermolytic hyperkeratosis (EHK) is an exceedingly rare dermatological condition, often presenting as solitary or multiple lesions in the vulvar region. Due to its clinical resemblance to other vulvar disorders, such as condyloma acuminatum, Bowenoid papulosis, and squamous cell carcinoma, vulvar [...] Read more.
Background: Vulvar epidermolytic hyperkeratosis (EHK) is an exceedingly rare dermatological condition, often presenting as solitary or multiple lesions in the vulvar region. Due to its clinical resemblance to other vulvar disorders, such as condyloma acuminatum, Bowenoid papulosis, and squamous cell carcinoma, vulvar EHK poses significant diagnostic challenges. While individual case reports and small case series have documented instances of vulvar EHK, comprehensive studies systematically consolidating the clinical, histopathological, and therapeutic aspects of this condition remain lacking. Objectives: To address this gap, this systematic review consolidates all available case reports and case series on vulvar EHK. The review aims to provide a comprehensive analysis of clinical presentations, histopathological features, diagnostic challenges, treatment approaches, and patient outcomes. Methods: We conducted a systematic review following the PRISMA guidelines. We searched multiple databases (PubMed, Web of Science, Scopus) for studies published up to 30 September 2024. Only case reports and case series with histopathologically confirmed vulvar EHK were included, as no higher-level studies (e.g., randomized controlled trials or cohort studies) were available due to the rarity of this condition. Exclusion criteria were male cases, oral EHK or other unrelated conditions, and literature reviews. We extracted and analyzed data on: patient demographics, time to diagnosis, anatomical distribution, clinical presentation, associated symptoms, histopathological features, patient history, risk factors, HPV status, treatment, and outcomes. Risk of bias was assessed using the CARE checklist and JBI Checklist for Case Series. Additionally, original clinical and histopathological images from our department were included to enhance the review. Results: A total of 19 studies, encompassing 30 cases of histopathologically confirmed vulvar EHK, were identified. Most cases presented with hyperkeratotic plaques and papules localized on the labia majora. Histopathological analysis consistently revealed hyperkeratosis, acanthosis, and vacuolar degeneration in the granular and spinous layers. Misdiagnosis was common, with lesions frequently mistaken for condyloma acuminatum or other vulvar neoplasms. Conservative management, including observation and topical therapies, was associated with disease stability in asymptomatic cases, while surgical excision demonstrated complete remission in all cases where it was employed. The rarity of vulvar EHK and reliance on case reports and series limit the generalizability of findings. Conclusions: Vulvar EHK is often misdiagnosed due to its similarity to malignancies and sexually transmitted infections. This review, the first of its kind, highlights the importance of prompt histopathological diagnosis to avoid the psychological impact of a cancer or sexually transmitted disease diagnosis and unnecessary, distressing, or aggressive treatments. Further research is needed to explore the role of HPV in vulvar EHK and to establish standardized diagnostic and treatment guidelines. Full article
(This article belongs to the Section Dermatology)
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17 pages, 13549 KB  
Article
Deferred Lateral Margin Control in the Surgical Treatment of Genital Paget’s Disease and Lentiginous Vulvar Melanoma
by Pedro Redondo
J. Clin. Med. 2025, 14(1), 69; https://doi.org/10.3390/jcm14010069 - 26 Dec 2024
Cited by 1 | Viewed by 1670
Abstract
Background/Objectives: Some skin tumors can extend beyond their clinical appearance. This presents an additional challenge, especially when the affected area is the genital region, which is more difficult for both the patient and the physician to access and monitor due to its location [...] Read more.
Background/Objectives: Some skin tumors can extend beyond their clinical appearance. This presents an additional challenge, especially when the affected area is the genital region, which is more difficult for both the patient and the physician to access and monitor due to its location and anatomical characteristics. The treatment of these lesions is complex, and literature postulates Mohs surgery as the best therapeutic option. Methods: We describe our experience in two patients with the resection of vulvar lentiginous melanoma and genital extramammary Paget’s disease, using a method of deferred lateral margin control in the surgical treatment. Results: The “spaghetti technique”(ST) initially removing a small strip from all lateral margins of the lesion, which is then closed directly while awaiting the paraffin histological result. In a second stage, the tumors within those margins are removed, and immediate reconstruction is performed. The final oncological and functional result was satisfactory, with no notable side effects. Conclusions: This method is suited for large, poorly defined superficial tumors in the genital, perineal, and perianal regions, where a frozen section study would be slow and burdensome for the patient and surgeon. The ST preserves healthy tissue and can be performed by any surgeon and pathologist without additional training, and is more comfortable for patients, avoiding prolonged open wounds during multiple steps of tumor excision. Full article
(This article belongs to the Section Dermatology)
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7 pages, 5674 KB  
Case Report
Vulvar Metastasis in Renal Cell Carcinoma: A Case Report Highlighting the Aggressive Nature of Clear Cell Renal Cell Carcinoma
by Andreea Boiangiu, Ana-Maria Cioca, Gabriel-Petre Gorecki, Romina-Marina Sima, Liana Pleș, Marius-Bogdan Novac, Ionut-Simion Coman, Valentin-Titus Grigorean, Vasile Lungu, Mihai-Teodor Georgescu and George-Alexandru Filipescu
Curr. Oncol. 2025, 32(1), 4; https://doi.org/10.3390/curroncol32010004 - 25 Dec 2024
Viewed by 1419
Abstract
Vulvar cancer is one of the rarest gynecological malignancies. The development of this condition can be associated with either dysplasia linked to human papillomavirus (HPV), primarily affecting younger women, or vulvar dermatoses such as lichen sclerosus, which predominantly affect older women. Over the [...] Read more.
Vulvar cancer is one of the rarest gynecological malignancies. The development of this condition can be associated with either dysplasia linked to human papillomavirus (HPV), primarily affecting younger women, or vulvar dermatoses such as lichen sclerosus, which predominantly affect older women. Over the last decade, the incidence of vulvar cancer has risen by 0.6% annually, while the relative survival rate has declined. Although metastasis to the vulva is uncommon, it can occur, particularly from cancers in nearby organs such as the cervix, bladder, rectum, or anus. More rarely, metastases from breast cancer and renal cell carcinoma have been reported in the vulva. Vaginal metastases from clear cell renal carcinoma are especially rare. In this article, we present the case of a 56-year-old patient diagnosed with clear cell renal carcinoma, who came to our clinic with a lesion on the right labia, which was identified as a metastasis originating from the kidney. Given the rarity of genital metastases in renal cancer, such cases should be examined and discussed to encourage further research and studies. Full article
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16 pages, 29464 KB  
Review
Molecular Subtypes of Vulvar Squamous Cell Carcinoma: The Significance of HPV-Independent/p53 Wild Type
by Lars-Christian Horn, Christine E. Brambs, Blake Gilks, Lien Hoang, Naveena Singh, Grit Gesine Ruth Hiller, Kathrin Hering, Jessica N. McAlpine, Amy Jamieson, Mona Alfaraidi, Bahriye Aktas, Nadja Dornhöfer and Anne Kathrin Höhn
Cancers 2024, 16(24), 4216; https://doi.org/10.3390/cancers16244216 - 18 Dec 2024
Cited by 5 | Viewed by 2289
Abstract
Vulvar carcinoma is a rare disease, meeting the criteria for a “rare cancer”, but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this [...] Read more.
Vulvar carcinoma is a rare disease, meeting the criteria for a “rare cancer”, but its incidence is increasing, especially in women <60 years of age. Squamous cell carcinoma (VSCC) accounts for the overwhelming majority of vulvar carcinomas and is the focus of this review. As with many cancers, the increased understanding of molecular events during tumorigenesis has led to the emergence of the molecular subclassification of VSCC, which is subclassified into tumors that arise secondary to high-risk human papillomavirus infection (HPV-associated, or HPVa) and those that arise independently of HPV (HPVi), most commonly in the setting of a chronic inflammatory condition of the vulvar skin. This latter group of HPVi VSCC arises in most cases secondary to mutations in TP53, but recently, attention has focused on the uncommon TP53 wild-type HPVi VSCC. These three molecular subtypes of VSCC (HPVa, HPVi p53 abnormal, and HPVi p53 wild type), as well as their precursor lesions, cannot be diagnosed based on a routine histopathological examination or immunostaining for p53 and p16 as surrogate markers for TP53 mutation and high-risk HPV infection, respectively, are required. The molecular subtyping of VSCC shows high reproducibility and provides important prognostic information. HPVa VSCC has the most favorable prognosis, while HPVi VSCC with TP53 mutations (p53abn) has the worst prognosis, and HPVi VSCC with wild-type TP53 (p53wt) has an intermediate prognosis. In this review, we discuss the evidence supporting this molecular subclassification and its implications for the diagnosis and treatment of VSCC and its precursors. Full article
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