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Primary malignant melanoma of the vagina accounts for less than 0.3% of all melanomas and approximately 4% of vaginal malignancies. We present a case of a 61-year-old female who presented with complaints of difficulty in urination and a polyp arising from the vagina. Local examination showed a polyp arising from the lateral vaginal wall and a hymenal tag. Histopathological examination of the polyp showed a neoplasm simulating a leomorphic sarcoma. The hymenal tag showed classical features of malignant melanoma. Immunohistochemistry with S100 and HMB45 confirmed malignant melanoma in the vaginal polyp. We report this case, on account of its rarity and unusual phenotypic profile, which may lead to a delayed or alternate diagnosis. Primary malignant melanoma of the vagina needs early accurate diagnosis and management due to its aggressive nature. Keywords: Vaginal melanoma, Mucosal melanoma, Vaginal polyp, Sarcomatous polyp.

Vaginectomy is surgery with limited indications. Usually, it is performed with concurrent hysterectomy even if the uterus is not affected by the neoplastic disease. However, it is possible to spare the uterine corpus and connect it to a neovagina. We present a nulliparous patient with vaginal

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.

Primary malignant melanomas (MM) originating from the gynecological tract are rare. They respond poorly to immunotherapy when compared with cutaneous MM. This study reports two cases. The first is of a 54-year-old woman with a cervical amelanotic polypoid mass who was diagnosed as having stage IB1 cervical melanoma according to the International Federation of Gynecology and Obstetrics system. At 17 months post-surgery, a computed tomography examination revealed recurrence of a 68 mm pelvic tumor. The second case is of a 37-year-old woman with a 7 cm hemorrhagic mass on the vaginal wall. The patient was diagnosed as having stage IV vaginal melanoma according to the American Joint Committee on Cancer definition. Both patients received nivolumab therapy, programmed cell death receptor 1 monoclonal antibodies, and the tumors almost disappeared. These cases may add the possibility of using colposcopy with narrow-band imaging and positron-emission tomography to diagnose and evaluate primary MM.

Melanomas of female genital tract are rare tumors with poor prognosis. While BRAF-V600E is the most common pathogenic mutation seen in cutaneous sun-exposed melanomas, mucosal and anogenital melanomas usually lack BRAF mutations and instead they harbor KIT alterations. The American Joint Committee on Cancer staging guideline (AJCC eighth edition) recommends using cutaneous melanoma guidelines for vulvar melanoma staging and does not provide any recommendations for vaginal melanoma staging. The aim of this study is to investigate the mutational status of invasive melanomas arising from different anatomic sites in lower female genital tract (vulvar hair-bearing skin, glabrous skin, vagina and urethra) in a group of 37 patients. Tumors were analyzed using a DNA targeted next-generation sequencing panel covering the 21 most common genes and mutation hotspots in melanomas. The most common genetic alterations in invasive melanomas of lower female genital tract are KIT (32%), TP53 (22%), and NF1 (19%). Overall 66% (21/32) of cases showed a pathogenic alteration in at least one of the MAPK pathway genes. No statistical significance seen between different primary tumor sites and the frequency of the oncogenic mutations, nor were any significant differences found by mutation status. Only one case of urethral melanoma showed a BRAF non-V600E mutation (D594G). Our results suggest a similar molecular pathogenesis and overall survival in melanomas arising from lower female genital tract, irrespective of their exact location in the urogenital area. Future classifications of melanoma should consider grouping vulvar melanomas with mucosal rather than cutaneous melanomas.

Background Malignant melanoma of the lower genital tract is a rare disease known to have a poor prognosis. Because of the high rate of distant metastasis and unsatisfactory survival benefit, a more conservative treatment approach, instead of extensive surgery, may be warranted. Gynecological melanoma is a radioresistant tumor, an ideal disease to test the biological efficacy of carbon ion radiotherapy (CIRT). Aim To report our preliminary experience with CIRT in the treatment of gynecological melanoma at the National Center of Oncological Hadrontherapy (CNAO). Patients and methods Between January 2016 and February 2017, four patients were admitted for CIRT at CNAO. A case of cervical melanoma was treated with palliative aim because of large volume macroscopic disease, while three cases of vaginal melanoma were irradiated with a total dose of 68.8 Gy (relative biological effectiveness) in 16 fractions delivered over 4 weeks (4 days a week). Results The age of women ranged between 49 and 72 (median=60.5 years) years. Treatment was well tolerated in all patients and all women completed the scheduled treatment course. During CIRT, toxicity was mild. For patients with vaginal disease, local control was 10.23 and 12.6 months, while that for cervical malignant melanoma was 7.3 months. All patients experienced systemic progression, with median distant metastasis-free survival of 11.7 months. The median overall survival for the whole patient group was 11.41 months. Conclusion In our first experiences, CIRT appears to be a safe non-invasive option for malignant melanoma of the lower genital tract, but more data and longer follow-up are necessary in order to evaluate the effectiveness and late effects.

Vaginal mucosa represents a rare site for primary melanoma. These neoplasms more commonly occur in the postmenopausal period, usually presenting with vaginal discharge, bleeding, or palpable mass. We report a case of an 89-year-old woman presenting with vaginal bleeding and a non-pigmented lesion in the lower third of the vagina at the gynaecological examination. A PAP smear and tissue incisional biopsy were concurrently performed. The cytological sample showed a subpopulation of non-cohesive, atypical epithelioid cells suggestive for malignancy. The histological examination showed the same morphological characteristics in the neoplastic population widely underlying the vaginal epithelium, with scattered intraepithelial nests and single elements. In both samples, there was no evidence of melanin pigment within the malignant cells. Immunohistochemical analysis performed on the tissue biopsy demonstrated a strong and diffuse positivity for melanocytic markers (HMB-45, S-100, Melan-A), confirming the diagnosis of primary amelanotic vaginal melanoma.

A 73-year-old woman with metastatic vaginal mucosal melanoma that had progressed on ipilimumab and nivolumab experienced clinical and radiographic complete response to dual checkpoint inhibitor immunotherapy given in combination with high-dose plus low-dose radiation. General characteristics and treatment options in this disease are highlighted.

Objectives: Due to the rarity of vulvar/vaginal melanoma (VVM), current therapeutic strategies mimics that of cutaneous melanoma (CM) without scientific rationale. Currently, immuno-oncology (IO) is a front-line treatment option for advanced melanoma, however data are limited for IO outcomes in advanced VVM. Considering 5-year survival for vulvar (58%) and vaginal (27%) melanoma is significantly inferior to cutaneous melanoma (81%), this calls into question the assumed similarity of these malignancies. As such, our goal is to compare molecular profiles of VVM with CM and explore the significance of IO agents on survival. Methods: Samples were analyzed using next-generation sequencing (NextSeq, 592 Genes and WES, NovaSEQ), IHC and WTS (NovaSeq) (Caris Life Sciences, Phoenix, AZ). PD-L1 expression was tested by IHC using 28-8 (Agilent) and SP-142 (Spring Biosciences) (positive cut-off ≥1%). MSI was tested by FA, IHC and NGS. TMB was measured by totaling somatic mutations per tumor (TMB-high cut-off ≥10 mutations per MB). Immune cell fraction was calculated by QuantiSeq (Finotello 2019, Genome Medicine). Survival was extracted from insurance claims data and calculated from time of IO treatment to last contact using Kaplan-Meier survival curves. Statistical significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons. Results: Molecular analysis was performed on 171 VVM and 5255 CM between 1998 and 2020. Median age for VVM and CM was 65 and 63, respectively. A total of 114 (66.7%) VVM and 3538 (67.3%) CM were metastatic at time of diagnosis. Immunogenicity of VVM was significantly lower than CM, demonstrated by an absence of high tumor mutation burden (0% vs 48%) and a decrease in PD-L1 expression (34.1% vs 45.2%) (Fig 1A). Adaptive immune gene expression was lower in VVM compared to CM (Fig 1B). By QuantiSeq, the cell fractions for type I macrophages and C8+ T-cells were significantly lower in VVM compared to CM (Fig 1C). Median survival was shorter for VVM than for CM (19 vs 37 months, p=.058; Fig 1D). VVM also demonstrated significantly (p Download : Download high-res image (316KB) Download : Download full-size image Conclusions: VVM represents a distinct molecular profile from CM with a less favorable immune phenotype demonstrated by absence of TMB-high, lower rates of PD-L1 positivity, and lower adaptive immune gene expression and cell fractions of effector T-cells and immune promoting macrophages. Compared with CM, patients with VVM were found to have significantly worse survival when treated with IO therapy. Though IO has been a mainstay of treatment in recent years, these findings suggest that new therapeutic strategies are needed.

Background Melanomas originating from gynecologic sites (MOGS) are rare mucosal melanomas originating from the vulva, vagina, and cervix. MOGS are associated with a poor survival rate and limited therapeutic options, as patients often present an advanced disease stage. MiRNAs (miRs) are a class of small, non-coding RNA molecules composed of 21–23 nucleotides that control expression of target genes via post-transcriptional regulation and can exhibit dysregulated expression in cancer. Patterns of miR expression and their effects on disease progression have not yet been explored in the setting of MOGS. We hypothesize a unique miR expression profile exists in MOGS that can mediate disease progression via interaction with target genes. Methods RNA was isolated from formalin fixed, paraffin embedded tissue samples of human vaginal and vulvar melanoma for comparison to normal adjacent vaginal mucosal tissue (NAT) and primary cutaneous melanoma (PCM), respectively. miR expression was then quantified using the NanoString human miRNA assay. Common experimentally validated gene targets of differentially expressed (DE) miRs were identified using miRNet, and pathway analysis was completed to examine potential downstream effects of dysregulated miR expression. Results Comparison of miR expression in vaginal melanoma to NAT revealed 25 DE miRs (fold change > 1.5, p 2, p Conclusions The results of this study support miRNAs as important potential regulators of gene expression in vaginal and vulvar melanomas that can contribute to tumor progression, tumor immunogenicity, and response to current immunotherapies. Ethics Approval This study was approved by the Ohio State University Institutional Review Board, approval #2007C0015.

Given the rarity of vaginal melanoma (VM), sparse retrospective data guide current clinical management. Standard treatment for localized disease involves wide local excision with negative margins, but due to multifocality of disease, local invasion, and anatomic constraints, it is often difficult to achieve negative margins without more extensive surgery including potentially pelvic exenteration. Additionally, despite aggressive loco-regional multi-modality therapy with surgery and with or without adjuvant radiation therapy (RT), outcomes remain poor for VM with high rates of distant recurrence. Radiation therapy has also evolved for melanoma, suggesting higher dose per fraction may overcome relative radioresistance and promote immunogenicity. More recently immunotherapy (IO) has shown promise in treating mucosal melanoma. As a result, treatment selection for these patients can be challenging given the needs to balance the morbidity of local therapies with propensity for distant metastatic disease and overall poor outcomes. Herein, we present two cases of vaginal melanoma treated at comprehensive cancer centers managed with a multi-modality approach of stereotactic body radiation therapy (SBRT) with concurrent IO with or without surgical debulking. Local treatment was safe and effective option for these patients with vaginal melanoma and can be considered in addition to enrollment on clinical trials during multi-disciplinary discussions of care.

Introduction Vulvar and vaginal melanomas are rare cancers of the female genital tract and account for 1% to 3% of all melanomas diagnosed in women. Due to the rarity of the disease, few data are available on the clinical and pathologic features of these cancers. Furthermore, treatment options are generally based on extrapolations of the information available for the more common cutaneous counterparts. Surgery represents the mainstay of treatment for lower genital tract melanoma. Moreover, the role of sentinel lymph node (SLN) assessment is controversial because no prospective data are available. Evidence acquisition Data were collected from MEDLINE, EMBASE, Web of Sciences and Scopus databases. On July 10, 2020, we used the search comprising the terms "vulvar melanoma", "genital melanoma" and "vulvovaginal melanoma" including only studies in which SLN biopsy was performed. Evidence synthesis Ten retrospective studies have been found. No randomized trials have been reported. The studies included 132 patients while only 63 (47%) undergone SLN. 99mTC with or without blue dye followed by ultrastaging was highly accurate and is currently the gold standard. Mean detection rate was 98.3%. No clear evidence supported the execution of back lymphadenectomy (after SLN mapping), in fact, extrapolating data from cutaneous melanomas of other sites, completion of lymphadenectomy does not confer a melanoma-specific survival advantage. Conclusions Although the small amount of available data, sentinel lymph node procedure is feasible and capable of identifying patients who have occult lymph node metastases. However, the potential role of the sentinel lymph node procedure as an alternative method of lymph node staging in patients with vulvar or vaginal melanoma needs further investigation.

Introduction Malignant melanoma, which arises from melanocytes or pigment cells, is one of the most common forms of epithelial cancer. Cutaneous and noncutaneous melanomas differ clinically and genetically. Mucosal melanomas are rare. In the female genital tract, the most frequent location of melanoma is the vulva, whereas the vagina is seldom affected. The occult nature of their anatomical location contributes to the late presentation and late diagnosis of vaginal melanoma, resulting in an exceedingly poor patient prognosis. The present study describes the incidence, symptoms, management, and prognosis of women in Pakistan with malignant melanoma of the vulva, vagina, and cervix. Materials and methods The Hospital Information System of Shaukat Khanam Memorial Cancer Hospital and Research Center was searched electronically to identify patients diagnosed with malignant melanoma from January 1995 to December 2017. Patients with cutaneous malignant melanoma, multiple primary tumors, and metastases to the female genital tract from primary tumors located elsewhere were excluded. All included patients had been diagnosed with primary malignant melanoma of the female genital tract. Results The search of medical records identified 271 patients with malignant melanoma, of whom 13 had primary malignant melanomas of the female genital tract. Of these 13 patients, nine, three, and one had primary vaginal, vulvar, and cervical melanomas, respectively. Median age at presentation was 60 years (range, 30-70 years), with 10 patients being post-menopausal. The most common presentations were per-vaginal bleeding and per-vaginal discharge (five patients each). The mean duration of symptoms was 7.46 months. Seven patients underwent wide local excision. Six patients had nodular type malignant melanoma, two had superficial spreading type, and five were unclassified. Nine patients had pathological T4 disease, and two had pathological T3. Mean Breslow depth was 5.4 millimeters (mm), with 10 patients having tumor depth >4 mm. Eight patients were positive for the microscopic involvement of margins. The mean time to recurrence was 11.8 months (range, 1-24 months), and the mean time to metastasis was 17.6 months (range, 2-44 months). The median survival after surgery was 25 months (range, 2-75 months). Conclusion This study is the first to report the incidence, symptoms, management, and prognosis of patients in Pakistan with malignant melanoma of the female genital tract. Meta-analyses and prospective multicenter studies are needed.

Introduction/Background Primary vaginal melanoma is a rare carcinoma, representing less than 3% of vaginal carcinomas. It normally presents in postmenopausal women with vaginal bleeding and discharge. No standard of treatment has been established in literature, with poor prognosis after diagnosis, with overall survival rate less then 12 months. Methodology 62 years old female was referred to our center due to postmenopausal bleeding. Hysteroscopy of uterine cavity was unremarkable, however pigmented lesions in the vagina were revealed. Biopsy confirmed a diagnosis of primary vaginal melanoma. Imaging studies with CT and MRI scan of pelvis; abdomen and thorax have not shown spread of the disease. Results were evaluated by a multidisciplinary team, which recommended surgical therapy. A combined laparotomy and vaginal en bloc resection with radical hysterectomy, bilateral salpingo-oophorectomy and total colpectomy was preformed. Additionally omentectomy, pelvic lymphadenectomy and biopsy of sentinel inguinal lymph nodes were performed. Results Histopathological examination revealed primary vaginal melanoma in situ with no signs of distal spread, maximum invasion at 1,1 mm, with 10 mm negative margins. No additional therapy was indicated. 6 month after procedure the patient is recovering well, with no sign of relapse. Abdominal ultrasound at check up was unremarkable. Conclusion Primary vaginal melanoma is a rare carcinoma that can present as postmenopausal bleeding. Our case report highlights that vagina should be evaluated in case of unremarkable examination of uterine cavity. As no standard of treatment has been established, good preoperative imaging and multidisciplinary approach should be considered. Radical excision is the best approach if no signs of distal spread are present. Disclosure Nothing to disclose

Introduction/Background Vaginal malignant melaona is rare non-cutaneous melanoma. It account less than 5% of vaginal cancers and 0.5% of all malignant melanomas. I experienced 2 cases of primary malignant melanoma. Methodology Case 1: 58 years old patient was referred due to vaginal black discoloration. She was noticed black discoloration 3 months ago at local OBGY clinical. 3 months later, local clinical doctor said black discoloration increased and recommended to our hospital. Punch biopsy was done on several black colored vaginal surface. Case 2: 62 years old patients visited my office due to vaginal discharge. There was black discolortaion spreading whole vaginal surface including uterine cervix. Punch biopsy was done on vagina and uterine cervix. Results I did Robot assisted radical hysterectomy with pelvic lymph node dissection. I did upper 1/3 vaginal dissection via intraperitoneal approach and via vaginal approach I did total vaginectomy. Plastic surgeon did vulvovaginal reconstruction surgery. Conclusion 1st case there was pelvic lymph node positive and 2nd case was lymph node negative. I did adjuvant immounotherapy on 1st case patient and did not done any adjuvant therapy on 2nd patient. Disclosure Nothing to disclose

Vaginal melanomas are extremely rare gynaecological malignancies. They are seen in advanced age and commonly present with vaginal discharge in postmenopausal women. Due to the rarity of the disease no standard management is described in the literature. However, surgical excision has been performed in most cases. We present a 77-year-old patient who presented with postmenopausal bleeding for 2 months. She was otherwise healthy. Examination revealed black colour growth in the anterior vagina of 2.5x 2 x 1 cm. complete excision of the tumor was done by hysterocolpectomy where the uterus was removed abdominally similar to the radical hysterectomy and vaginal approach removed the lower and middle vagina. The postoperative period was uneventful and is currently being followed up. Histology confirmed the diagnosis of vaginal melanoma.

Highlights • Surgical approach is standard of care, topical imiquimod still experimental for mucosal melanoma. • Imiquimod beneficial for local control of disease if surgery not an option for MIS of vulva/ vagina. • In situ and invasive vulvovaginal melanoma have a high risk for recurrence even years later. • Long-term follow-up after topical imiquimod treatment needed as metastasis can arise years later., The primary treatment of both in situ and invasive vulvar melanoma is wide local excision of the primary neoplasm. However, this can be a surgical challenge for size, multifocal presentation with proximity to urethra or anus and tendency for local recurrence. The data on adjuvant therapy for vulvar MIS is very limited. A 69-year-old patient with melanoma of the vulva underwent a simple vulvectomy with positive margins in peri-clitoral area, followed by modified radical vulvectomy and bilateral inguinofemoral sentinel lymph node dissection with negative margins. She was later diagnosed with MIS of the vulva on different locations and had multiple wide local excisions over several years. One lesion was close to the urethra and a complete excision was difficult. Topical imiquimod × 16 weeks (5% cream) was given. The regimen was augmented from 3 to 5 times weekly. Complete resolution was found at 16 weeks and patient was disease free for 4 years. Recently however, a vaginal melanoma was detected. Imiquimod appeared to be beneficial in the treatment of melanoma in situ of the vulva/ vagina when surgical options were not feasible producing local control of disease with the remaining risk for local and distant metastasis. Metastasis can appear years later, therefore long-term follow-up of patients treated with topical imiquimod is needed.

Primary vaginal melanoma is a rare mucosal neoplasm, which is more aggressive than cutaneous melanoma. Information regarding its morphologic patterns is limited. In particular, the rhabdoid phenotype, mostly observed in metastatic or recurrent cutaneous melanomas, has yet to be reported at this anatomic location. Hence, a potential diagnostic difficulty may arise because of the inability to recognize this unusual histologic variant and its immunohistochemical aberrance. In this report, we describe the case of a primary vaginal melanoma in a 62-year-old woman, who exhibited both rhabdoid and small blue round cell morphologies, absence of S100 protein, and aberrant expression of desmin, CD56, and FLI-1. This report can facilitate the task of expanding the morphologic spectrum of vaginal melanoma, and prevent misdiagnosis and inadequate medical treatment.

Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Conclusion: Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease.

Vaginal malignant melanoma is a rare form of mucosal melanoma, and accounts for only

Primary malignant melanoma of the vagina is a rare entity which constitutes less than 3% of vaginal cancer and only 0.3-0.8% of all melanomas in women. It has a high risk of local recurrence and distant metastasis. Once a recurrence is noted, survival is extremely poor. This article reports a case of primary vaginal melanoma with longer survival. As long-time survival of stage II vaginal melanoma is a rare phenomenon, this case is a unique one in Bangladesh; emphasizing on both importance of routine gynaecological examination for any suspicious pigmented lesions in the vagina as well as the necessity of further research on validating treatment protocols. Journal of Armed Forces Medical College Bangladesh Vol.15 (1) 2019: 114-115

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

Primary malignant melanoma of the vagina is an extremely uncommon malignancy comprising of less than 10% malignancies of the female genital tract and 0.3% of all melanomas. Melanoblasts are neural crest derivatives and are notorious for causing primary cutaneous neoplasms. However, they involve virtually every organ of the body including eye, intestines and ocular mucosa, probably due to aberrancies in cell migration. Vagina is a rare site and primary melanoma of the vagina occurs in postmenopausal women with vaginal discharge, bleeding, or mass as common presenting complaints. Only a handful of case reports are available describing this entity on biopsy and PAP smear samples; however, fine needle aspiration has seldom been discussed. In the present report we discuss a case of an elderly female who complained of mass protruding through the vaginal opening, FNAC was done from the mass as well as from the right inguinal lymph node. An extensive clinicoradiological workup, and immunohistochemical confirmation is essential to rule out metastatic lesions and confirm primary. Diagn. Cytopathol. 2017;45:252-256. © 2016 Wiley Periodicals, Inc.

Objectives To assess clinical and pathologic features that impact outcome in patients with vaginal melanoma. Methods This is a retrospective review of vaginal melanoma cases treated at single institution between 1990 – 2015. Clinical and pathological characteristics were reviewed. Progression-free survival (PFS) and overall survival (OS) were calculated from the first treatment date. Results Fifty-two patients with median age of 60.5 years (32.0–86.0) were identified. Using the AJCC clinical staging, 11.5% were stage I, 61.6% were stage II, 19.2% were stage III and 7.7% were stage IV. The median tumor size was 3.0 cm with median tumor thickness 8.0 mm. 81% experienced disease recurrence with 40.5% local recurrence, 23.8% distant recurrence and 35.7% both. Overall, the median PFS was 8.9 months with a 5-year PFS of 16%. The OS was 19.8 months with a 5-year OS of 18%. 44 patients underwent surgery as part of their primary therapy while 8 women did not have surgery. Patients who underwent surgery had a median OS 20.7 VS 9.3 months for those who did not (p Conclusions Vaginal melanoma most commonly presents at an early stage but is still associated with poor outcomes. Patients who have localized disease, who are able to undergo primary surgical treatment and who undergo pelvic exenteration have longer OS.

Primary malignant melanoma (MM) accounts for 1% of all cancers, and only 3% to 7% of these tumors occur in the female genital tract. Data are limited with respect to the basis for treatment recommendations because of the rarity of MM. The overall prognosis of melanomas of the female genital tract is very poor. Two cases of MM of the female genital tract are presented. The first case is of a 70-year-old female patient who complained of left thigh pain and underwent magnetic resonance imaging that showed cervical cancer with involvement of the vagina, bladder, and parametrium, in addition to multiple bony metastases of the proximal femur, acetabulum, and both iliac bones. The second case is of a 35-year-old female patient who suffered from vaginal bleeding for 5 months, and she was diagnosed as having primary vaginal melanoma. The patient underwent radical surgery and two additional surgeries because of recurrence of cancer in both inguinal areas. After surgery, the patient received adjuvant immunotherapy, radiation therapy, and chemotherapy. In both the aforementioned cases, the pathologic diagnosis was made after immunohistochemical analysis, i.e., the tumor cells were stained with HMB-45 and S100, and were found to be positive for both immunostains.

Genital melanoma is a rare pathology. We present the experience of two comprehensive cancer centers in Lyon (France) in the management of genital melanoma in order to identify prognostic factors and optimal treatments. Between April 1992 and Mars 2014, 16 patients with a primary genital melanoma were referred to our department. Nine patients presented a vaginal melanoma, six vulvar melanomas and only one cervical melanoma. The median dimension of the lesion was 33.7 mm (5–100 mm). The AJCC stage ranged from IB to IIIC. 12 cases were the classic dark-blue flat melanoma and the other 4 cases were an atypical amelanotic tumor. Wide local surgery was performed in nine patients. A radical surgery was performed in six patients. In the large cervical melanoma, radiotherapy was performed as first-line treatment. In all the patients regional lymph node staging was performed. Adjuvant treatment was realized in nine patients. Two patients are alive without recurrence. Only one patient was lost to the first follow-up. The other 13 patients experienced a rapid recurrence. The median disease-free survival and the median overall survival were 11.8 months (2–49 m) and of 30.4 m (11–144 m), respectively. The disease-free survival and overall survival could be linked to a clinical presentation (Breslow thickness and morphology of lesion) associated to the early diagnosis. In our small series, the most important prognosis factor remains the tumor thickness. These rare lesions should be treated in experienced centers in order to improve their prognostic.

Primary vaginal malignant melanoma is a rare form of non-cutaneous melanoma [1]. It accounts for less than 1% of all malignant melanomas and less than 3% of all primary malignant tumours of the vagina [2]. The age of the onset of vaginal melanoma has been reported to range from 38 to 90 years, with most patients being diagnosed between the ages of 60 and 80 years [1]. Patients commonly complain of vaginal bleeding, vaginal discharge or a palpable mass. Unfortunately, vaginal melanomas are often only diagnosed at an advanced stage and treatment options include local excision with wide margins, radical surgery, radiotherapy, chemotherapy and immunotherapy. Currently, no standard treatment protocol has been established and the prognosis remains poor [1]. The present study describes a case of malignant melanoma of vagina and its management (Figs. 1, ​,2).2). Open in a separate window Fig. 1 Malignant melanoma of vagina

Mucosal melanomas are rare, accounting for only 1.4% of all melanomas. Only 18% of mucosal melanomas are vulvovaginal in origin, making it exceedingly rare. Mucosal melanomas typically carry a worse prognosis than those arising from cutaneous sites with a higher risk of recurrence and disseminated disease. We report a rare case of vaginal melanoma presenting as postmenopausal bleeding and discuss management of this disease.

Vaginal melanoma is an extremely rare entity. It is an aggressive disease with a poor prognosis and short-term survival related to high rate of local and distant recurrences. Treatment modalities are not codified and include surgery, radiotherapy and chemotherapy. Radiotherapy is always used as adjuvant treatment after wide local excision, but there are little data about its use as an exclusive treatment or after partial surgery. We report the case of vaginal melanoma in 31-year-old Arabic woman. The patient refused radical surgery, and partial surgery was performed followed by hypofractionated external beam radiotherapy at the dose of 20 Gy in 5 daily fractions of 5 Gy week (biologic effective dose = 53.33 Gy for melanoma α/β = 3), to the entire pelvis including inguinal lymph nodes; then, the tumor bed was boosted by high-dose-rate brachytherapy at the dose of 28 Gy in 4 fractions of 7 Gy. After 12 months of follow-up, the patient is free of local or distant recurrence. Radiotherapy is an effective therapeutic modality of vaginal melanoma, especially when radical surgery is not feasible or refused. Radiation oncologist must integrate radio-biologic characteristics of melanoma in the choice of dose fractionation.

Objectives The aim of this work was to determine molecular characteristics and specifically, the frequency of BRAF, C-KIT, and NRAS mutations in vulvar and vaginal melanomas. Methods A retrospective review of all cases of vulvar and vaginal melanoma between 2002 and 2013 was performed. We reviewed the clinical and histological characteristics of all cases and performed genotyping studies on cases that had tissue available for the study, using next-generation sequencing. Results We identified 33 vulvar and 11 vaginal melanomas in women with mean ages 58 and 61 years, respectively. Next-generation sequencing analysis on 20 cases (15 vulvar and 5 vaginal) identified a BRAF mutation in 7.6%, C-KIT mutation in 27.6%, NRAS mutation in 27.6%, and TP53 mutation in 7.6% of the vulvar cases. We detected only a single TP53 mutation in the vaginal cases. We did not identify any statistically significant relationship between the mutation status and patients' outcome, depth of invasion, ulceration, stage at presentation, or lymph node metastasis. Conclusions BRAF mutations are infrequent, whereas C-KIT and NRAS mutations are seen with higher frequency in vulvar melanomas than melanomas of other sites. These mutations can be considered as potential therapeutic targets in patients harboring them. Further studies are necessary to increase our understanding of mutational events occurring in melanoma of the lower female genital tract and their relationship with clinical parameters/outcome.

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 vulvo-vaginal 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.

We report the case of a 70-year-old woman with vaginal melanoma and multiple metastases in the lung. After the third dose of nivolumab, decreased room-air resting arterial oxygen saturation with bilateral basal fine crackles on auscultation developed despite the absence of respiratory symptoms. Computed tomography showed ground-glass opacities with airspace consolidations scattered with a peculiar distribution, and most were observed around the existing metastatic tumors in the lung. From the 42nd day to the 56th day after the last administration of nivolumab, she received dexamethasone 1-2 mg/body for the prevention of adverse events after stereotactic radiation for brain metastasis. At 3 months after the last administration of nivolumab, a computed tomography scan revealed improvement of the pneumonia and a decreased size and number of metastatic lesions in the lung, although some lesions showed enlargement. Further examination is needed to clarify the relationship between the pattern of pneumonia after Nivo therapy and clinical effects.

A 43-year-old woman was referred to an oculoplastic surgeon for the evaluation of 2 small pigmented lesions in the tarsal conjunctiva. She underwent a biopsy of the lesions, both of which were found to be consistent with metastatic melanoma. Follow-up with the patient revealed that she had been hospitalized for balance issues and headaches. An MRI of her brain revealed a hemorrhagic mass and several smaller foci suspicious for metastatic lesions. A thorough workup included an evaluation for bloody vaginal discharge. Biopsy of a pigmented portion of the vaginal mucosa lesion revealed BRAF-positive melanoma. This was determined to be the primary site of her malignant metastatic melanoma, which caused her death within 6 months of presentation.

Immune checkpoint inhibitors might be therapeutic options for unresectable or metastatic melanomas of the vulva and vagina but data available in the literature in these melanomas are very limited 1 2 3 4. The aim of this retrospective study was to investigate the effect of anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed death 1 (PD-1) antibodies in patients treated in our Skin Cancer Department for unresectable or metastatic vulvar or vaginal melanoma since 2013. This article is protected by copyright. All rights reserved.

Malignant melanoma of vagina is a rare tumor with incidence rate of only 0.46 cases per one million women per year and less than 250 cases have been reported in medical literature till date. It has a notoriously aggressive behavior and is associated with a high risk of local recurrence and distant metastasis. At present, there are various treatment options for this disease but no standard guideline. It accounts for less than 1% of all malignant melanoma and less than 3% of all primary malignant tumors of the vagina. Conventional imaging techniques i.e. computed tomography, may be sub-optimal in evaluating a small volume of tumor, which may lead to inaccurate staging of a loco-regional tumor. The optimal treatment for vaginal melanoma is a subject of debate. Malignant melanoma of the vagina is a disease of postmenopausal women, with 75% of women being more than 50 years of age. Here, we present a case of primary vaginal malignant melanoma in a 35 year woman located in lower 1/3rd of the vagina.

Objective To describe the characteristics of primary vaginal melanoma patients in the Surveillance, Epidemiology, and End Result database and to determine the outcome from the treatment approaches. Materials/Methods From the Surveillance, Epidemiology, and End Result registry, 201 patients with vaginal melanoma were identified. Patients’ characteristics and prognostic factors including age, race, extent of surgery, and use of radiation therapy were obtained. Results The median age was 68 years (range, 28–100 years). The population was 73% white, 11% black, and 16% Asian/American Indian. International Federation of Gynecology and Obstetrics staging results were stage I (46%), stage II (18%), stage III (3%), stage IVA (3%), stage IVB (12%), and unknown (18%). Treatment approach included surgical resection of the primary site in 70%, whereas 35% of the patients underwent lymph node resection. Approximately 40% of the patients received radiotherapy, which was primarily used in the adjuvant setting. Overall survival at 2 and 5 years was 24% and 15%, respectively. Presence of lymph nodes at diagnosis was associated with worse overall survival (hazard ratio, 1.98; P = 0.02). Adjuvant radiation did not offer a statistically significant overall survival advantage compared to surgery alone. Conclusions Vaginal melanoma is a rare diagnosis primarily affecting the elderly. Overall survival is low even for patients presenting with disease limited to the vagina. Lymph node involvement at diagnosis is strongly predictive of worse overall survival. Most patients are treated with surgical resection with varying use of adjuvant radiotherapy. Further research is needed to identify the etiology and improve the outcome of this aggressive disease.

We aimed to compare the differences in demographic features, clinicopathologic features, and survival in patients with vulvar/vaginal melanoma versus cutaneous melanoma with a special emphasis on race.Data were obtained from the Surveillance Epidemiology and End Results database from 1973 to 2008. Kaplan-Meier curves and Cox multivariate model were used for statistical analysis.Seven hundred sixty-two patients with vulvar/vaginal melanoma and 55,485 patients with cutaneous melanoma patients were included in the study. Twenty-eight patients of the vulvar/vaginal group and 334 patients of the cutaneous group were black (3.6% vs 0.6%, respectively). The median age at the time of diagnosis was 68 years in the vulvar/vaginal group and 52 years in the cutaneous group (P0.0001). Three hundred fifty patients (45.9%) in the vulvar/vaginal and 46,499 patients (83.8%) in the cutaneous group presented with localized disease (P0.0001), whereas 64 patients (8.4%) in the vulvar/vaginal group and 1520 patients (2.7%) in cutaneous group presented with advanced disease (P = 0.0081). The median survival of the black patients was 16 months in the vulvar/vaginal group and 124 months in the cutaneous melanoma group (P0.0001). The median survival in the nonblack population was 39 months in the vulvar/vaginal group compared to 319 months in the cutaneous melanoma group (P0.0001). In multivariate analysis performed for patients between 1988 and 2008, age, stage, and positive lymph nodes were negative independent prognostic factors for survival in vulvar/vaginal melanoma; whereas age, race, stage, radiation therapy, and lymph node positivity were negative prognostic factors in cutaneous melanoma.These findings emphasize that cutaneous and vulvar/vaginal melanomas have different clinicopathologic features and survival patterns.

Introduction: Malignant melanoma, which has a highly malignant potential, is a tumor of the skin and mucosal membranes. Malignant melanomas of the female genital tract, including the vulva and vagina, are rare. Their overall prognosis is poor and is worse than that for cutaneous melanomas. Cases presentation: Clinical data for 3 patients with primary malignant melanoma are presented. Diagnosis was based on histologic and immunohistochemical examinations. Case 1 was a 45 year-old women with cervical polyp and excision revealed malignant melanoma. Case 2 was 46-year-old woman with cervical and vaginal melanoma and the third was a 64 year-old women with lentiginous melanoma of the clitoris. One patient was treated with surgery and adjuvant chemotherapy, and two patients received systemic chemotherapy. Conclusion: Although malignant melanoma of the female genital tract is uncommon, literature review shows that prognosis is poor than at other sites, most probably due to more advanced disease at diagnosis. This presentation highlights that early diagnosis by physicians at this relatively rare site is of crucial importance since it may result in improved outcome, similar to that of melanoma at more common sites.

Objective We report our experience with vulvar (Vu) and vaginal (Va) melanoma, with review of surgical and adjuvant therapy guidelines and description of our use of neoadjuvant therapy in selected cases. Methods We reviewed patients seen at Mayo Clinic for management of Vu or Va melanoma, January 1993–February 2012. Surgical treatment, pathologic and outcome data were abstracted. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan–Meier method, and compared between subgroups using the log-rank test. Results 50 patients underwent surgery for primary or recurrent melanoma (Vu=36, Va=14). The 5-year OS rate was 30.9%, with median OS of 3.3years. Adjuvant therapy was given to 30.6% of Vu cases with varying combinations of agents. Among Vu patients, after adjusting for node status and depth of invasion, adjuvant therapy was not associated with improved OS (p=0.39) or RFS (p=0.31). Preoperative chemotherapy was used in 2 Va cases. Despite temozolomide followed by exenteration for a 4cm multi-focal lesion, one patient died within 3months. The second patient, with a 2cm vaginal lesion, demonstrated a partial response to carboplatin and paclitaxel (CP). After local excision and lymphadenectomy she received additional CP with bevacizumab and remains disease free at 5years. CP with bevacizumab was also used in 1 Vu case with a solitary 5cm midline lesion. She underwent vulvectomy after a partial response, received additional CP and bevacizumab postoperatively, and remains without disease at 2years. Conclusion Preoperative chemotherapy with CP and bevacizumab may improve treatment outcomes, particularly for Va and large Vu lesions.