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Although rare, vulvar melanoma is the second most common histological type of vulvar cancer, representing around 10% of all malignant tumors involving the vulva presenting typically in post-menopausal women. The data on vulvar melanoma consists almost entirely of case studies and small retrospective series. A standardized approach to the diagnosis and management of vulvar melanoma is not available. In this paper, a case of vulvar melanoma in remission is described and a review of the current literature is presented. A 73-year-old, G5P5 (5-0-0-5), complained of a 3-year history of intense vaginal pruritus. A biopsy was done at the site of the hyperpigmented patch revealing vulvar melanoma. CT scan was done before surgery and revealed negative lymph node invasion nor metastasis. The patient underwent a radical vulvectomy followed by adjuvant radiotherapy which offered remission of disease for 5 years. [ABSTRACT FROM AUTHOR]

Background: Vulvar melanoma and vaginal melanoma are rare and difficult to treat. We describe the last three decades in a cohort predominantly treated surgically with adjuvant therapy. Methods: All new patients between 1993 and 2021 followed until 2024. Collection of demographic and oncologic data allowed comparisons and Kaplan-Meier method was used to evaluate overall survival (OS) and progression free survival (PFS) stratified by adjuvant therapy type, diagnosis before and after 2011, and between vulvar and vaginal melanomas. Results: Consultation for 63/72 patients (87.5 %) were for primary treatment. Most patients had vulvar melanoma (50/72, 69.4 %), received surgery (65/72, 90.3 %), and adjuvant treatment (40/72, 55.6 %) with immunotherapy, chemotherapy, and/or targeted therapy. Median survival for 63 patients presenting for primary treatment was 54.2 months, and 9/13 patients who were disease free after five years later received adjuvant immunotherapy. Survival did not vary by adjuvant therapy type or diagnosis after 2011 but was significantly less for vaginal melanoma. Following recurrence seven patients experienced complete response including three patients receiving combined nivolumab with ipilimumab and two nivolumab alone experienced. Conclusions: Survival was not significantly different by adjuvant therapy type or after 2011. Most patients who were disease-free five years after surgery had received adjuvant therapy. Seven patients experienced complete responses to therapy after recurrence of whom five received immune checkpoint inhibitors. Although survival is not improved as in cutaneous melanomas by immune checkpoint inhibitors, signal continues for the use of immune checkpoint inhibitors in gynecologic melanomas.

Abstract Background Vulvar and vaginal melanoma (VuM & VaM) is a rare gynecologic malignancy with high mortality but low effectiveness to checkpoint immunotherapy compared to cutaneous melanoma. This article aims to elucidate the role of the disordered immune microenvironment in cancer progression in VuM. Methods At first, this article applied single-cell RNA sequencing (scRNA-seq) to the VuM obtained from a 68-year-old female patient, and constructed a single-cell atlas of VuM consist of 12,243 single cells. Then this article explores the genomic complexity and core signal channel in VuM microenvironment. Results This article provides new insights about the pathogenesis of VuM based on single-cell resolution data. It was found that the activation of CD8+ T cell contributed to induce tumor angiogenesis and immune escape, and the activation of the antigen-presenting molecular function participated in melanoma metastasis. Conclusion This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration.

Background: Vulvar and vaginal melanoma (VuM & VaM) is a rare gynecologic malignancy with high mortality but low effectiveness to checkpoint immunotherapy compared to cutaneous melanoma. This article aims to elucidate the role of the disordered immune microenvironment in cancer progression in VuM. Methods: At first, this article applied single-cell RNA sequencing (scRNA-seq) to the VuM obtained from a 68-year-old female patient, and constructed a single-cell atlas of VuM consist of 12,243 single cells. Then this article explores the genomic complexity and core signal channel in VuM microenvironment. Results: This article provides new insights about the pathogenesis of VuM based on single-cell resolution data. It was found that the activation of CD8+ T cell contributed to induce tumor angiogenesis and immune escape, and the activation of the antigen-presenting molecular function participated in melanoma metastasis. Conclusion: This article provided new insights into underlining VuM molecular regulation and potential signaling involved in immunotherapy, which would benefit the clinical practice and administration. [ABSTRACT FROM AUTHOR]

The aim of this article is to describe an island flap, harvested from the inguinal fold, which can be used for vulvar reconstruction: the inguinal fold island flap (IFI flap). IFI flap is indicated for reconstruction of defects of vaginal vestibule and labia minora and it could be raised bilaterally safeguarding regional symmetry and avoiding vaginal introitus or urethral distortion. This flap has been utilized to reconstruct defects after vulvar melanoma and squamous cell carcinoma resections and in one case to restore vaginal vestibule anatomy in a revision surgery in a transgender woman. IFI flap is an example of an "aesthetic/functional" reconstruction which could be proposed to younger patients too. [ABSTRACT FROM AUTHOR]

Objective. This multicenter study aimed to investigate the role of preoperative lymphatic mapping and sentinel node biopsy (SNB) as well as the impact of negative SNB on loco-regional control and survival in vulvar melanoma patients with clinically negative nodes (cN0). Methods. Patients who had a proven vulvar melanoma with a Breslow thickness of 1–4 mm, cN0 and underwent a preoperative lymphatic mapping followed by SNB between July 2013 and March 2021 were retrospectively included. Groin recurrence and mortality rate were calculated as absolute and relative frequency. Disease-free survival (DFS) and overall survival (OS) were assessed by the Kaplan-Meier method. We provided a systematic review, searching among PubMed/Medline and Embase libraries. A total of 6 studies were identified (48 patients). Results. A total of 18 women were included. Preoperative planar images showed 51 SNs in 28 groins. Additional SPECT/CT images were acquired in 5/18 cases; SNs were identified pre- and intra-operatively in all cases. A total of 65 SNs were excised from 28 groins. A total of 13/18 (72.2%) patients (21/28 groins, 75%) had negative SNs with no groin recurrences and 12/13 (92.3%) were still alive at last follow-up. Five out of the 18 (27.8%) patients (7/28 groins, 25%) had positive SNs, 2/5 (40%) patients died of cancer after 26.2 and 33.8 months, respectively. The median DFS and OS for the entire cohort were 17.9 months (95% CI, 10.3–19.9) and 65.0 months (95% CI, 26.2-infinite), respectively. The probability of DFS and OS at 3 years were 15.5% (95% CI, 2.6–38.7) and 64.3% (95% CI, 15.5–90.2), respectively. Conclusions. The use of preoperative lymphatic mapping followed by SNB permits a precise and minimally invasive surgical approach in cN0 vulvar melanoma patients. Negative SNB is associated with low risk of groin relapse and good survival. • Lymphoscintigraphy and sentinel node biopsy allow a personalized surgical approach in cN0 vulvar melanoma patients. • This technique could be a valid alternative to radical surgery, thus avoiding post-operative complications. • A negative sentinel node biopsy is associated with low risk of groin relapse and good survival. [ABSTRACT FROM AUTHOR]

Objective: This article presents a review of the current diagnosis and treatment of vulvar melanoma in detail to provide useful references for the diagnosis and treatment of the disease in the future. Mechanism: In this review, the author first specifies the topic of the article and the content covered. PubMed was searched for a series of keyword combinations related to the topic, and there was extensive reading of search engine- and database-derived literature from 1970–2022 related to the vulvar melanoma guidelines, including randomized clinical studies, observational studies, and basic research. Based on the published content, the articles were screened according to the year of publication, the number of citations, and the publishing unit. The data and content needed in each article were collected. Finally, the collected data were summarized to provide an in-depth introduction to vulvar melanoma, a rare disease, covering the aspects of clinical features, diagnosis, staging, treatment and prognosis. Findings in Brief: Through this review, we gain a comprehensive understanding of the current diagnosis and treatment of vulvar melanoma and the breakthrough direction of future research. Conclusions: At present, the main diagnostic methods in cases of vulvar melanoma include macroscopic examination, dermoscopy, microscopy, histopathology and imaging examination. The main treatment modalities for vulvar melanoma are surgery, radiotherapy, chemotherapy, immune checkpoint inhibitors, targeted therapy and immune modulators.

Simple Summary: Vulvar melanoma (VM) is a rare and fatal disease. Knowledge of this disease is poor and, consequently, so is knowledge of the prognosis. Our aim was to collect evidence on VM with particular attention to its molecular profile and related clinical and therapeutic implications. Malignant melanoma is a fatal disease that affects all skin sites. Among these, vulvar melanoma (VM) is a rare gynecological condition that accounts for 5% of all vulvar neoplasms. VM primarily affects older Caucasian women and its relationship to sun exposure is undefined. Diagnosis is defined by biopsy but many clinical, dermatoscopic, and confocal microscopic features can guide doctors. The molecular profile is characterized by the KIT mutation, revealed by all of the technologies that are used (classical sequencing, next-generation sequencing, and immunohistochemical staining). BRAF and NRAS mutations are also common in VM. All of these mutations are possible therapeutic targets. Today, surgery remains the first treatment choice for primary VM. The role of neoadjuvant and adjuvant therapy is scarce and the treatment of relapses is widely debated. [ABSTRACT FROM AUTHOR]

Vulvar malignant melanoma (VMM) is uncommon and poses a significant management challenge. Here, we presented a case of VMM managed by surgery, chemoradiation, and planned for targeted therapy. A 70-year-old woman with underlying diabetes mellitus and hypertension presented with a black-colored exophytic growth around her left vulva for two months. Initial biopsy confirmed malignant melanoma with positive staining for S100, HMB 45, and Melan A. An imaging study showed that the disease was localized to the vulva. She underwent bilateral radical vulvectomy and bilateral inguinofemoral lymph node dissection followed by radiotherapy. She had a locoregional disease recurrence, which was subsequently managed by palliative perineal radiotherapy, chemotherapy, and planned for immunotherapy. Vulvar malignant melanoma is a rare and aggressive tumor, with a poor overall prognosis, and high recurrence rate. Adjuvant chemotherapy, radiotherapy, and immunotherapy may be beneficial for local recurrence and distant metastasis cases. Molecular Analysis has a potential role in targeted therapy to improve the survival and outcome of the patient. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Background: Vulvar melanoma and vaginal melanoma are rare and difficult to treat. We describe the last three decades in a cohort predominantly treated surgically with adjuvant therapy., Methods: All new patients between 1993 and 2021 followed until 2024. Collection of demographic and oncologic data allowed comparisons and Kaplan-Meier method was used to evaluate overall survival (OS) and progression free survival (PFS) stratified by adjuvant therapy type, diagnosis before and after 2011, and between vulvar and vaginal melanomas., Results: Consultation for 63/72 patients (87.5 %) were for primary treatment. Most patients had vulvar melanoma (50/72, 69.4 %), received surgery (65/72, 90.3 %), and adjuvant treatment (40/72, 55.6 %) with immunotherapy, chemotherapy, and/or targeted therapy. Median survival for 63 patients presenting for primary treatment was 54.2 months, and 9/13 patients who were disease free after five years later received adjuvant immunotherapy. Survival did not vary by adjuvant therapy type or diagnosis after 2011 but was significantly less for vaginal melanoma. Following recurrence seven patients experienced complete response including three patients receiving combined nivolumab with ipilimumab and two nivolumab alone experienced., Conclusions: Survival was not significantly different by adjuvant therapy type or after 2011. Most patients who were disease-free five years after surgery had received adjuvant therapy. Seven patients experienced complete responses to therapy after recurrence of whom five received immune checkpoint inhibitors. Although survival is not improved as in cutaneous melanomas by immune checkpoint inhibitors, signal continues for the use of immune checkpoint inhibitors in gynecologic melanomas., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Vulvar malignant melanoma is the second most common subtype of vulvar cancer, accounting for 5–10% of all vulvar cancers. The prognosis is still very poor, although some advances have been achieved in the last years. One of the most significant changes in its management has been the development of less invasive surgical techniques that diminish the risk of postoperative morbidity and long-lasting sequelae. In this article, we review the surgical management of the pathology, based on the comment of 3 cases with vulvar melanoma treated at our institution.

Introduction. Malignant skin melanoma accounts for 1% of all human malignancies. Vulvar melanoma constitutes less than 1% of all melanomas and it is the second most common malignant tumour of the vulva, accounting for 10% of all vulvar malignancies. Usually, it is detected in a later stage compared to other skin melanomas because of its anatomical location and represents a real diagnostic and treatment challenge for dermatologists and gynaecologists. Case presentation. We present a rare clinical case of a 27-year-old woman with pigmented malignant melanoma affecting the left labium majora. Conclusions. Malignant vulvar melanoma in women under the age of 45 years is rare. It is more aggressive than other types of malignant skin melanomas because of its relatively late diagnosis. Knowledge of the disease will improve the medical care provided and patients’ prognosis.

Vulvar malignant melanoma is the second most common subtype of vulvar cancer, accounting for 5–10% of all vulvar cancers. The prognosis is still very poor, although some advances have been achieved in the last years. One of the most significant changes in its management has been the development of less invasive surgical techniques that diminish the risk of postoperative morbidity and long-lasting sequelae. In this article, we review the surgical management of the pathology, based on the comment of 3 cases with vulvar melanoma treated at our institution. [ABSTRACT FROM AUTHOR]

To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM). This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis. The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-risk clinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40–56%) and 31% (95% CI 23–39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno- or targeted therapy. Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed. • Vulvar melanoma is a rare gynaecological cancer with poor prognosis due to its high metastatic potential. • The only potentially curative option for localized disease is complete surgical resection with negative margins. • Sentinel lymph node biopsy is only recommended in order to direct adjuvant treatment. • Analysis for targetable mutations should be incorporated into routine clinical testing for vulvar melanoma. • Immunotherapy with anti-PD1 or anti-CTLA4 should be considered in metastatic or non-resectable vulvar melanoma. [ABSTRACT FROM AUTHOR]

An atypical cellular blue nevus, a benign mass, may sometimes transform into a malignant melanoma. Here, we report a rare case of melanoma arising in a large congenital vulvar blue nevus. A 28‐year‐old Chinese woman presented to our hospital with a chief complaint of a vulvar mass that had persisted for 8 years. The patient underwent extensive local excision, followed by reconstructive surgery of the female reproductive tract. The mass was diagnosed as being a vulvar malignant melanoma. Postoperatively, the patient received interferon immunotherapy and recovered without complications. No evidence of recurrence was observed after 32 months of follow‐up. Our case thus shows that comprehensive treatment with surgery supplemented by immunotherapy can be effective against a malignant melanoma arising in a vulvar blue nevus. [ABSTRACT FROM AUTHOR]

Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted.

Abstract Background Although the most commonly recommended treatment for melanoma and extramammary Paget’s disease (EMPD) of the genital region is wide surgical excision of the lesion, the procedure is highly invasive and can lead to functional and sexual problems. Alternative treatments have been used for local control when wide local excision was not feasible. Here, we describe four patients with genital malignancies who were treated with boron neutron capture therapy (BNCT). Methods The four patients included one patient with vulvar melanoma (VM) and three with genital EMPD. They underwent BNCT at the Kyoto University Research Reactor between 2005 and 2014 using para-boronophenylalanine as the boron delivery agent. They were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin/mucosal doses. Results All patients showed similar tumor and normal tissue responses following BNCT and achieved complete responses within 6 months. The most severe normal tissue response was moderate skin erosion during the first 2 months, which diminished gradually thereafter. Dysuria or contact pain persisted for 2 months and resolved completely by 4 months. Conclusions Treating VM and EMPD with BNCT resulted in complete local tumor control. Based on our clinical experience, we conclude that BNCT is a promising treatment for primary VM and EMPD of the genital region. Trial registration numbers UMIN000005124

Background: Malignant tumor of the vulva is the fourth gynecological malignancy in frequency. Close to 70% of all vulvar malignancies are related to high‐risk human papillomavirus (HPV) infection. Methods: A search for non‐HPV‐related malignant tumors of the vulva was performed in the last 20 years (2000‐2020) in the pathology database of a single tertiary institution. We aim to estimate the prevalence of non‐HPV‐related malignancies in our population, describe clinicopathological features of these tumors and investigate the expression of some potential therapeutic targets. Results: A total of 71 patients were recovered; 26 patients (36%) had the diagnosis of extramammary Paget disease, 17 patients (24%) had basal cell carcinomas, 17 patients (24%) had primary melanomas, 10 patients (14%) had metastatic disease to the vulva and one patient (1%) had a primary dermatofibrosarcoma protuberans. Fifty‐four percent of patients with extramammary Paget disease had a secondary malignancy and 12.5% had invasive disease. Programmed death‐ligand 1 (PDL‐1) was positive in seven out of nine primary melanomas and Her2/neu was overexpressed in six out of seven extramammary Paget disease. Conclusion: Non‐HPV‐related malignancies are important differential diagnoses in patient with vulvar lesions. Additional research is necessary to further understand these complex malignancies and potential new therapeutic targets. [ABSTRACT FROM AUTHOR]

Metastatic vulvar melanoma is a rare and aggressive disease and survival is usually poor. Vulvar melanomas harbor BRAF V600 mutations only infrequently; consequently, target therapy is a rare therapeutic option and immunotherapy usually has only a weak effect. On the other hand, KIT mutations are rare in cutaneous melanomas, but relatively frequent in mucosal melanomas, particularly in vulvar-vaginal melanomas, and can be a therapeutic target. Herein, we report a clinical case of a patient with metastatic vulvar melanoma, harboring an exon 17 c-KIT mutation, treated with avapritinib (BLU-285) – a highly potent and selective oral kinase inhibitor designed to treat imatinib-resistant gastro-intestinal stromal tumors (GIST) by targeting KIT/PDGFRα activation loop mutants (exons 17/18). After failure of the combination of ipilimumab + nivolumab first and then nivolumab alone, the patient received avapritinib 300 mg/daily for central nervous system (CNS), lymph-nodal, right adrenal gland, lung, and subcutaneous metastases. Best response was partial remission, according to RECIST 1.1 criteria. Time to treatment progression was 11 months. Main toxicities were grade 2 cutaneous vasculitis that required avapritinib discontinuation, and grade 2 uveitis of unknown origin, treated by vitrectomy and empiric antibiotic and antiviral therapy due to negative cultural tests. Uveitis was detected at the time of progression and therapy was definitively discontinued. In conclusion, avapritinib proved to be effective even in the presence of a pretreated disease, a high tumor burden, and brain metastases. In our experience, treatment was feasible and toxicity manageable. Considering the lack of effective therapies and the poor outcome of the disease, determination of c-KIT mutations should be performed routinely in cases of metastatic mucosal melanoma. [ABSTRACT FROM AUTHOR]

Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can distinguish melanomas originating in the mucous membranes and located in areas not exposed to the sun, namely the vulvo-vaginal melanomas. By contrast with cutaneous melanomas, the incidence of these types of melanomas is constant, being diagnosed in females in their late sixties. While hairy skin and glabrous skin melanomas of the vulva account for 5% of all cancers located in the vulva, melanomas of the vagina and urethra are particularly rare conditions. The location in areas less accessible to periodic inspection determines their diagnosis in advanced stages, often metastatic. Moreover, despite the large number of drugs newly approved in recent decades for the treatment of cutaneous melanoma, especially in the category of biological drugs, the mortality of vulvo-vaginal melanomas has remained almost constant. This, together with the absence of specific treatment guidelines due to the lack of a sufficient number of cases to conduct randomized clinical trials, makes melanomas with this localization a discouraging diagnosis, associated with a very poor prognosis. Our aim is therefore to draw attention to this oftentimes overlooked entity in order to encourage the community to employ various strategies meant to increase research in this area. By highlighting the main risk factors of vulvar and vaginal melanomas, as well as the clinical manifestations and molecular changes underlying these neoplasms, ideally novel therapeutic schemes will, in time, be brought into effect.

The incidence of vulvar carcinoma increases with age, though elderly women receive less aggressive cancer therapies and fewer strategies aimed at cancer prevention. Furthermore, elderly women dual enrolled in Medicaid-Medicare experience poor survival rates for vulvar carcinoma. Herein, we provide recommendations for the prevention of and guidelines for the multidisciplinary care of vulvar carcinoma. Prevention of vulvar carcinoma can be categorized into primary, secondary, and tertiary prevention. Primary prevention consists of vaccination, secondary prevention consists of screening, and tertiary prevention is aimed at the management of premalignant and early-stage lesions., Competing Interests: None., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of Women’s Dermatologic Society.)

The case report of a black-skinned 62 years female patient assisted in Conrado Benítez García Teaching Provincial Oncological Hospital in Santiago de Cuba is described due to an increase of volume in the outer lip that began to hurt. A excisional biopsy was carried out which result revealed a vulvar melanoma. She was referred to the Oncological gynecology service where she was indicated treatment with chemotherapy and immunotherapy for being a non-surgical tumor. Four chemotherapy cycles were administered with good response and stability. Her care continued through follow-up. [ABSTRACT FROM AUTHOR]

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches.

Introduction: Mucosal melanoma is rare and associated with poorer prognosis in comparison to conventional melanoma subtypes. Little is known about the prognostic significance as well as possible associations between PARP1 and immunologic response in mucosal melanoma. Methods: PARP1, PD-L1 and IDO1 immunostains were performed on 192 mucosal melanomas including 86 vulvar, 89 sinonasal, and 17 anorectal melanomas. Results: By Kaplan–Meier analyses, high PARP1 expression correlated with worse overall and melanoma-specific survival (log-rank p values = 0.026 and 0.047, respectively). Tumors with combined PARP1 and IDO1 high expression correlated with worse overall and melanoma-specific survival (p = 0.015, 0.0034 respectively). By multivariate analyses, high PARP1 expression remained a predictor of worse survival independent of stage. By Fisher’s exact test, high PARP1 expression correlated with highly mitogenic tumors (p = 0.02). High tumoral PD-L1 and IDO1 expression were associated with ulcerated primary tumors (p = 0.019, 0.0019, respectively). By linear regression analyses, correlations between PARP1 expression versus IDO1 expression (p = 0.0001) and mitotic index (p = 0.0052) were observed. Conclusion: Increased expression of PARP1 is an independent negative prognostic marker in mucosal melanomas. The association between PARP1 and IDO1 and their combined adverse prognostic role raise the potential of combined therapy in mucosal melanoma.

Vulvar melanoma is a rare and deadly cancer in women, and the prognosis is often poor. There are limited studies on the dermoscopic features of vulvar melanoma. Described criteria include the presence of blue, gray, or white colors. Herein we present the clinical and dermoscopic characteristics of a hypopigmented and heavily pigmented nodule in a 92-year-old and an 80-year-old woman. Dermoscopy in the former revealed structureless milky-red to white areas, remnants of brown pigmentation at the base and polymorphic vessels, while the latter displayed structureless blue-gray areas with black dots and peripheral lines at the base. In both cases, histopathology revealed a stage III melanoma. Our two cases along with a review of the literature suggest that the dermoscopic features described for diagnosing cutaneous nodular melanoma, apply also for vulvar melanoma. Clinicians should always raise the suspicion if observing plaques or nodules with a dermoscopic polymorphic vascular pattern and blue-black color on the genitals of postmenopausal women.

Aim of the study: In this retrospective cohort study we have examined differences in survival profiles with respect to the body mass index in patients with mucosal melanoma on immune checkpoint inhibitor therapy. Materials and methods: The primary outcome included the association between the body mass index and overall survival in patients with metastatic mucosal melanoma. The secondary outcomes included the clinical presentation and management of vulvar and vaginal melanomas with oral and anorectal mucosal melanomas, as well as the surgical and radiological management of vulvar and vaginal melanomas. Kaplan--Meier analysis and log-rank test were used for the assessment of overall survival. Results: The results showed that patients with mucosal melanoma whose body mass index was ≥25 had better overall survival (p = 0.02). Overall survival was different between vulvar/vaginal vs. oral mucosal melanoma (p = 0.02). Overall survival was not different between vulvar/vaginal vs. anorectal melanoma (p = 0.77). Some immune toxicities were specific to patients with vulvar/vaginal melanoma. Conclusions: Obesity is associated with improved survival in patients with metastatic mucosal melanoma, although findings can be heterogeneous depending on the subtype of mucosal melanoma. [ABSTRACT FROM AUTHOR]

Background: Genital melanosis may clinically mimic melanoma. Little is known about the potential risk for genital and nongenital melanoma in these patients.Objective: In this retrospective cohort study, we analyzed clinical and histologic data from patients with genital melanosis to better characterize these lesions and the risk they confer for genital and nongenital melanoma.Methods: In all, 41 patients were identified for a retrospective chart review and histologic analysis.Results: Genital melanosis can clinically mimic melanoma but the typical age of onset is younger than for genital melanoma. A majority of lesions were found to stabilize or regress over time. Five patients were found to have a history of melanoma, only 1 of which was in the genital region. Lesions from these patients were more likely to show melanocytes with suprabasal movement (P = .0101) and to have a higher melanocyte count (P < .0462).Limitations: We present a relatively small cohort of patients with an average follow-up of only 30.5 months.Conclusion: Patients with genital melanosis, and in particular those with any level of histologic atypia in the genital melanosis lesion, may require careful total body skin examinations for the possibility of melanoma in any body site. [ABSTRACT FROM AUTHOR]

Background: Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic melanoma (NGM) subtypes with the objective of identifying novel, targetable biomarkers.Methods: In total, 2304 samples of malignant melanoma that were submitted to Caris Life Sciences between 2009 and 2015 were reviewed. In situ hybridization and immunohistochemistry were used to assess copy numbers and protein expression of selected genes. Sequenced variants were analyzed using a proprietary cancer panel.Results: In total, 51 VVMs (14 vaginal and 37 vulvar melanomas) were compared with 2253 malignant NGMs, including 2127 cutaneous, 105 mucosal, and 21 acral melanomas. In VVMs, B-Raf proto-oncogene serine/threonine kinase (BRAF) was the most frequently mutated gene (26%) compared with 8.3% of mucosal NGMs (P = .008). In BRAF-mutated tumors, fewer VVMs (50%), compared with NGMs (82.1%), had a variant within the valine codon 600 (V600) domain. The KIT mutation rate was highest in VVMs (22%) compared with 3% in cutaneous (P < .001) and 8.8% in mucosal (P = .05) melanoma subtypes. NRAS mutations were rare in VVMs compared with cutaneous (25.9%; P = .009) and acral (40.6%; P = .002) melanoma subtypes. PD-L1 (56%) and PD-1 (75%) were frequently expressed in VVM, whereas PI3KCA pathway mutations and estrogen receptor/progesterone receptor expression were rare. Compared with VVMs that had KIT mutations, wild-type KIT VVMs were more likely to express molecular markers suggestive of platinum resistance (ERCC1), alkylating sensitivity (MGMT), and anthracycline sensitivity (TOP2A).Conclusions: The unique molecular features of VVM render this disease a distinct subtype of melanoma. Gene-based molecular therapy and immunotherapies may be promising and should be evaluated in clinical trials. Cancer 2017;123:1333-1344. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Melanoma of the vulva comprises around 3-4% of all melanoma cases in women, very rarely appearing before the age of 50. It belongs to the group of rare tumours in this location, comprising 8-10% of vulva tumours, and the estimated frequency of vulvar melanoma occurrence is 0.10/100 000 women-years. Among the factors that can predispose to developing melanoma of the vulva, we can distinguish chronic inflammatory diseases, virus infections (including HPV virus), factors causing vulva irritation and genetic susceptibility.The majority of melanomas of the vulva develop “de novo”, but they can also develop on the basis of previously existing pigmentary birthmarks. Most frequently, during physical examination pigmentary changes in the area of the vulva are found. However, in around 30% of cases melanoma does not have pigmentary traits. The depth of infiltration (invasion) is the crucial prognostic histological factor in melanoma. The treatment is based on surgery, the extent of which depends on the stage of tumour advancement. Supplemental treatment makes use of interleukin-2, interferon alpha, dacarbazine or paclitaxel with cisplatin or carboplatin. The case of a 64-year-old female patient with melanoma of the vulva area, who despite surgical treatment based on partial excision of the vulva with lymph glands and keeping a margin of healthy tissues, as well as supplemental therapy with interferon alpha, and who after a year was diagnosed with reoccurrence of the tumour in the area of the distal part of the urethra, is presented below. Continuation of the treatment is based on surgical excision of the front part of the vulva together with the distal part of the urethra and adjuvant chemotherapy treatment according to the docetaxel/carboplatin combination.

Objective To describe trends in incidence, treatment and survival of patients with basal cell carcinomas and melanomas of the vulva. Also to compare survival of vulvar and cutaneous melanoma patients. Methods All women with a vulvar malignancy between 1989 and 2012 were selected from the Dutch Cancer Registry ( n = 6436). Standardized incidence rates, estimated annual percentage change (EAPC) and 5-year relative survival rates were calculated for basal cell carcinomas (BCCs) and melanomas. Patients with vulvar melanomas were matched to women with cutaneous melanomas on period of diagnosis, age, Breslow thickness, tumour ulceration, lymph node status and distant metastases. Differences in survival were evaluated using Kaplan-Meier curves and the log rank test. Results 489 women were diagnosed with a BCC and 350 with a melanoma of the vulva. The EAPC in incidence for melanomas was 0.2% and 1.1% for BCCs. Eighty-six percent of patients with BCC underwent surgical treatment in 1989–2006 and 95% in 2005–2012. Forty-five percent with BCC and 79% with melanoma were treated in a referral centre. Five-year relative survival for BCCs was 100% and for melanomas survival increased from 37% (95%CI 28–47%) in 1989–1999 to 45% (95%CI: 37–54%) in 2000–2012. Five years after diagnosis survival of women with vulvar melanoma was 15% lower compared to matched cutaneous melanoma patients (p = 0.002). Conclusion No trends in age-adjusted incidence have been observed but more patients with BCC received surgical treatment over time. Having had vulvar BCC did not affect life expectancy. Well-known prognostic factors explained most of the differences in survival between cutaneous and vulvar melanoma patients, however a difference of 15% remained unexplained. [ABSTRACT FROM AUTHOR]

Female genital tract melanoma (FGTM) is a rare and aggressive melanocytic malignancy, and its clinico-pathological and prognostic features at different anatomic sites have not yet been fully described. We retrospectively analyzed and compared the clinico-pathological data and survival outcomes of patients with primary lower genital tract melanoma enrolled between January 2005 and December 2020. We identified 95 patients with FGTM, of whom 46 had vulvar melanomas (VuM), 43 had vaginal melanomas (VaM), and six had cervical melanomas (CM). The clinical characteristics of all 95 cases, including symptoms, single or multiple primary lesions, clinical stage, surgery, and histopathological characteristics of 62 primary untreated cases, including pigmentation, predominant cytology, histological pattern, mitotic figures, and tumor-infiltrating lymphocytes of VuM, VaM, and CM, differed significantly. In comparison, only trend differences in molecular alternations were evident (p = 0.077). Disease-specific survival (DSS) was 30.7% at 5 years (46.5%, 25.6%, and 44.4% for VuM, VaM and CM, respectively). Seventy-one (85.5%) patients experienced FGTM recurrence. The median time to the first recurrence was 11 months, and VaM recurred earlier than VM and CM (16, 6, and 10 months for VuM, VaM, and CM, respectively, p = 0.038). A univariate analysis of 50 cases revealed the negative factors of disease-specific survival (DSS), including the location of the vagina and the presence of ulceration, and the negative factors of recurrence-free survival (RFS), including multiple lesions, the presence of ulceration, and the presence of lymphovascular invasion. Multiple lesions showed a borderline correlation with DSS. A multivariate Cox regression analyses of 50 cases revealed that the presence of ulceration was associated with shorter DSS and RFS (yes vs. no, Hazard Ratio = 2.400 and 2.716, respectively). Vaginal location showed a significant correlation with DSS (Hazard Ratio = 2.750, p = 0.024). In conclusion, vulval, vaginal, and cervical melanomas may differ in terms of their clinico-pathological features and associations with DSS and RFS. Ulceration and vaginal location were significantly associated with shorter DSS, and ulceration was associated with an increased risk of FGTM recurrence., (Copyright © 2022. Published by Elsevier Inc.)

The soft tissue defects of the anterior perineum can be caused by tumour excision, trauma, burns, Fournier's gangrene and genital mutilation. Various reconstruction methods were described: vacuum-assisted closure, skin grafts and skin substitutes, pedicled or free flaps. In the case of defects following oncologic surgery, flaps are the reconstructive method of choice. We present the case of a 65 year-old woman diagnosed with stage III A vulvovaginal melanoma affecting also the distal urethra. Radical vulvectomy and en-bloc excision of the anterior third of the vagina and distal urethra, along with bilateral inguinal lymphadenectomy was performed. The resulting defect was covered with bilateral V-Y advancement gluteal fold flaps. A local vaginal recurrence appeared 18 months after surgery and was safely removed. The patient followed chemotherapy with Dacarbazine. The gluteal fold flap offered good defect coverage and survived completely. Follow-up period was two years without distant metastases. Functional result was excellent, urinary function being normal and patient satisfaction high. Due to the gluteal flap's advantages (appropriate thickness, good vascularity, minimal donor site morbidity, and same operative field allowing for shorter operating time), reconstruction of the anterior perineum after oncological resection with bilateral V-Y advancement gluteal flaps is a viable solution. [ABSTRACT FROM AUTHOR]

Vulvovaginal melanomas are rare tumors that account for a small fraction of all vulvovaginal cancers. Biologically, they seem to be similar to mucosal and acral melanomas of other sites. There are limited data specific to vulvovaginal melanomas, especially regarding systemic therapies. Most treatment decisions are based on extrapolation from data regarding cutaneous melanomas of other sites. It is reasonable to follow already established guidelines from other professional groups and societies. Outcomes tend to be worse compared with cutaneous melanomas likely because of the later presentation and physical biological characteristics of these tumors. [ABSTRACT FROM AUTHOR]

Background: Melanoma of the female genitalia has poor overall prognosis. Objective and methods: To examine prognostic factors influencing survival, the Duke Melanoma and Tumor Registry Databases were queried for patients who had received their clinical care at Duke University Medical Center, with a diagnosis of melanoma of the female genitalia, including vulva, vagina, and cervix, between 1970 and 2009. From this group, any available histopathologic specimens were procured for further review. Results: Eighty-five patients were identified. The median follow-up time was 8.8 years with 60% of the patients experiencing melanoma-related mortality at last follow-up. Survival rates at 1, 5, and 10 years were 85%, 51%, and 30%, respectively. The available histopathologic specimens from 36 cases were reviewed by a dermatopathologist (M.A.S.). Fifteen of 36 cases were notable for the presence of atypical melanocytic hyperplasia adjacent to the primary melanoma. Breslow depth, lymph node status, systemic therapy, and surgery were also examined for differences in survival distributions using the log-rank test. In general, survival was inversely correlated with Breslow depth, extent of nodal involvement, and provision of systemic therapy. A higher survival rate was observed among those who received wide local excision. Log-rank test demonstrated that survival between different decades of diagnosis was not significantly different. Limitations: Because of its small sample size, this study may be underpowered. Conclusion: Despite new treatments developed and attempted, there is no evidence that survival has improved over the past 40 years. In summary, patients with thinner melanomas amenable to surgical resection had a better prognosis than those with more extensive, metastatic disease at presentation. [ABSTRACT FROM AUTHOR]

Abstract: Intermittent sun exposure and sunburn are strong predictors of cutaneous malignant melanoma (CMM). On the other hand, melanomas may arise also in non-sun-exposed areas such as the vulva. However, little is known about a possible relationship between sun exposure and vulvar melanoma. Temporal and latitudinal dependencies of the incidence rates of vulvar melanoma were studied in comparison with those of CMM among Caucasians in Sweden, East Germany, USA and Victoria (Australia). The ratios of vulvar melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. The incidence rates of CMM have increased with time until recently, while those of vulvar melanoma have either decreased or remain constant. In USA vulvar melanoma incidence rates seem to increase from south to north, while for CMM incidence rates on sun exposed skin areas decrease from south to north. Comparison of latitudinal trends of the incidence rates of vulvar melanomas and CMM show opposite trends. Whenever CMM rates increase, either with time or with decreasing latitude (indicating increased sun exposure) the ratio of vulvar melanoma rates to CMM rates on exposed skin, seem to decrease. Thus, latitudinal trends seem to support the assumption that vulvar melanomas are not generated by UV radiation, and the possibility exists that solar UV radiation, probably via its role in vitamin D photosynthesis in exposed skin, may have a protective effect against vulvar melanoma and should be further investigated. [Copyright &y& Elsevier]

Vulvar melanoma is a rare malignant tumour. Its surgical excision is the mainstay of treatment whilst the surgical management of regional lymph nodes remains controversial; on the contrary elective inguinofemoral lymphadenectomy causes considerable morbidity. Lymphoscintigraphy (LS) and sentinel lymph node biopsy (SLNB) are accurate staging procedures of lymph node status in breast cancer and cutaneous melanoma patients. In this retrospective paper we report our experience of LS and SLNB in vulvar melanoma patients. Twenty-two consecutive patients with a diagnosis of vulvar melanoma were treated at our institute: patients with clinically positive groin nodes or with previous surgery on the primary tumour were excluded. Twelve were selected for our analysis. All patients underwent sentinel lymph node localization with LS the day before surgery and the surgical procedure of SLNB associated with radical surgery. Six patients had metastatic SLNB and in five of six (83.3%) it was the only positive node. In the other six patients SLNB was negative for metastatic disease. No skip metastases were observed. In SLNB negative patients the mean Breslow thickness was 2.06 mm (range: 0.60–7.10) and only one patient showed a high Breslow thickness (patient 8). In SLNB positive patients the mean Breslow thickness was 4.33 mm (1.8–6.0). Our data indicate that, even in vulvar melanoma, the sentinel lymph node pathological status predicts the pathological status of the remaining groin nodes and suggests that elective groin dissection can be spared in cases of a negative SLNB. Breslow thickness (<1 mm) was not predictive of negative nodes. [ABSTRACT FROM AUTHOR]

Mucosal melanomas (MM) are rare tumors, being less than 2% of all diagnosed melanomas, comprising a variegated group of malignancies arising from melanocytes in virtually all mucosal epithelia, even if more frequently found in oral and sino-nasal cavities, ano-rectum and female genitalia (vulva and vagina). To date, there is no consensus about the optimal management strategy of MM. Furthermore, the clinical rationale of molecular tumor characterization regarding BRAF, KIT or NRAS, as well as the therapeutic value of immunotherapy, chemotherapy and targeted therapy, has not yet been deeply explored and clearly established in MM. In this overview, focused on anorectal and genital MM as models of rare melanomas deserving of a multidisciplinary approach, we highlight the need of referring these patients to centers with experts in melanoma, anorectal and uro-genital cancers treatments. Taking into account the rarity, the poor outcomes and the lack of effective treatment options for MM, tailored research needs to be promptly promoted. [ABSTRACT FROM AUTHOR]

Abstract: Objectives.: Only few population-based incidence analyses of vulvar melanoma including the United States and Sweden are currently available. We studied the incidence of vulvar melanoma in a large population-based cancer registry of East Germany and compared our findings with the United States and Sweden. Methods.: We extracted vulvar melanoma registered between 1976 and 1989 in the former National Cancer Registry of the German Democratic Republic (GDR) and of three new East German cancer registries of the federal states of Sachsen, Brandenburg, and Mecklenburg-Vorpommern of the period 1998 to 2002. We calculated age-specific and age-standardized incidence rates using the World Standard Population. Results.: One hundred two cases (1976–1989, former GDR) and twenty-five cases of vulvar melanoma (1998–2002, three new federal states) were registered. The age-standardized incidence rate (World Standard Population) remained constant over the period from 1976 to 1989 and ranged between 0.26 and 0.52 cases per million. From 1998 to 2002, the incidence rate was 0.48 per million. The ratio of registered vulvar melanoma to skin melanoma was 1:71, and the ratio of vaginal melanoma to skin melanoma was 1:314. Age at diagnosis during the period 1976 to 1989 was lower among women with vulvar melanoma (median age 70 years) compared to women with vulvar tumors other than melanoma (median age 73 years). Conclusions.: The risk of vulvar melanoma was considerably lower in East Germany than in the United States and Sweden. Due to the rarity of vulvar melanoma, population-based cancer registries are hampered to study this tumor in detail. [Copyright &y& Elsevier]

Objectives: To update, assimilate, and bridge the contemporary literature on vulvar and cutaneous melanoma regarding diagnosis, staging, and therapy to provide a useful clinical reference for managing and counseling for affected patients.Materials and Methods: A computerized search for reports in the literature up to June 2003 was carried out using PubMed and MEDLINE databases. Multidisciplinary involvement was used in evaluating the available data and formulating conclusions.Results: More than 300 reports were reviewed. Diagnosis, staging, and therapy aspects of vulvar melanoma are summarized.Conclusions: Vulvar melanoma represents a subtype of cutaneous melanoma, with similar prognostic and staging factors. The most recent American Joint Committee on Cancer staging system for cutaneous melanoma is applicable to vulvar melanoma. Sentinel lymph node biopsy is reliable for staging the regional lymph node basin for vulvar melanoma. Standardized documentation of clinical and histopathologic parameters is needed to standardize grouping of cases for future comparison studies. [ABSTRACT FROM AUTHOR]

Vulvar melanoma is a rare tumour, of poorly known pathogenesis, which presents particularities compared to cutaneous melanoma: more frequently achromic and very often multifocal, it is of the lentiginous histological type (MLM), with in half of the cases lentiginous melanocytic hyperplasia at a distance., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can distinguish melanomas originating in the mucous membranes and located in areas not exposed to the sun, namely the vulvo-vaginal melanomas. By contrast with cutaneous melanomas, the incidence of these types of melanomas is constant, being diagnosed in females in their late sixties. While hairy skin and glabrous skin melanomas of the vulva account for 5% of all cancers located in the vulva, melanomas of the vagina and urethra are particularly rare conditions. The location in areas less accessible to periodic inspection determines their diagnosis in advanced stages, often metastatic. Moreover, despite the large number of drugs newly approved in recent decades for the treatment of cutaneous melanoma, especially in the category of biological drugs, the mortality of vulvo-vaginal melanomas has remained almost constant. This, together with the absence of specific treatment guidelines due to the lack of a sufficient number of cases to conduct randomized clinical trials, makes melanomas with this localization a discouraging diagnosis, associated with a very poor prognosis. Our aim is therefore to draw attention to this oftentimes overlooked entity in order to encourage the community to employ various strategies meant to increase research in this area. By highlighting the main risk factors of vulvar and vaginal melanomas, as well as the clinical manifestations and molecular changes underlying these neoplasms, ideally novel therapeutic schemes will, in time, be brought into effect. [ABSTRACT FROM AUTHOR]

Vulvar cancer (VC) is a rare neoplasm, usually arising in postmenopausal women, although human papilloma virus (HPV)-associated VC usually develop in younger women. Incidences of VCs are rising in many countries. Surgery is the cornerstone of early-stage VC management, whereas therapies for advanced VC are multimodal and not standardized, combining chemotherapy and radiotherapy to avoid exenterative surgery. Randomized controlled trials (RCTs) are scarce due to the rarity of the disease and prognosis has not improved. Hence, new therapies are needed to improve the outcomes of these patients. In recent years, improved knowledge regarding the crosstalk between neoplastic and tumor cells has allowed researchers to develop a novel therapeutic approach exploiting these molecular interactions. Both the innate and adaptive immune systems play a key role in anti-tumor immunesurveillance. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in multiple tumor types, improving survival rates and disease outcomes. In some gynecologic cancers (e.g., cervical cancer), many studies are showing promising results and a growing interest is emerging about the potential use of ICIs in VC. The aim of this manuscript is to summarize the latest developments in the field of VC immunoncology, to present the role of state-of-the-art ICIs in VC management and to discuss new potential immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]