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Akusherstvo I Ginekologiia 2015Malignant melanoma of the vulva is a rare disease with aggressive behavior and poor prognosis. It consist < 5% of all cases of melanoma in females, as the ratio of its...
Malignant melanoma of the vulva is a rare disease with aggressive behavior and poor prognosis. It consist < 5% of all cases of melanoma in females, as the ratio of its manifestation, compared with the cutaneous melanoma is 1:71. Higher risk of developing melanoma of the vulva is established in white women, as the peak of the incidence is between 60 and 70 years of age. Clinically, MM of the vulva manifests as asymptomatic pigmented, rarely a pigmented lesion, as the usual clinical form is superficial spreading MM and much less common nodular MM, which is associated with a poorer prognosis in. general. The diagnosis is confirmed by histological examination. Conduction of PCR and DNA analysis for detection of BRAF mutations, NRAS mutations and KIT amplification is also appropriate. Advanced age, black race, tumor size, tumor thickness, ulceration, presence of satellite lesions, involvement of adjacent organs (vagina, urethra), and the presence of regional or distant metastases are identified as the most important prognostic markers. Radical wide excision followed by bilateral lymphadenectomy id considered as the optimal therapeutic approach.
Topics: Female; GTP Phosphohydrolases; Humans; Lymph Node Excision; Melanoma; Membrane Proteins; Mutation; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-kit; Vulva; Vulvar Neoplasms
PubMed: 25909143
DOI: No ID Found -
Human Pathology Jan 2023Female genital tract melanoma (FGTM) is a rare and aggressive melanocytic malignancy, and its clinico-pathological and prognostic features at different anatomic sites...
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.
Topics: Humans; Female; Prognosis; Retrospective Studies; Melanoma; Skin Neoplasms; Vulvar Neoplasms; Vaginal Neoplasms; Uterine Cervical Neoplasms; Vagina
PubMed: 36370822
DOI: 10.1016/j.humpath.2022.11.002 -
Journal of Gynecologic Oncology Sep 2020Melanoma comprises 5% to 10% of vulvar cancers and prognosis is poor. The purpose of this study was to identify prognostic factors and treatment patterns for vulvar...
OBJECTIVE
Melanoma comprises 5% to 10% of vulvar cancers and prognosis is poor. The purpose of this study was to identify prognostic factors and treatment patterns for vulvar melanoma using the National Cancer Database (NCDB).
METHODS
The NCDB was queried for patients with invasive vulvar melanoma from 2004-2015. Descriptive statistics were generated to describe clinical and treatment details. Multivariable Cox regression and the Kaplan-Meier method were used to examine overall survival (OS).
RESULTS
1,917 patients with vulvar melanoma met inclusion criteria. Median follow-up time was 32 months (range, 0-151 months). Older age, larger tumor size, advanced disease stage, increased Charlson-Deyo comorbidity score, and care at a non-academic center were independent predictors for decreased OS. Surgical management of the primary site, lymph node surgery, and insurance provided a significant survival benefit. Use of immunotherapy for vulvar melanoma has increased over time. Two-year OS with immunotherapy in patients with distant metastatic disease was higher, although this did not reach statistical significance (33% vs. 12%, p=0.054).
CONCLUSIONS
Vulvar melanoma has a poor prognosis for those with regional and distant metastatic disease. Extent of disease, tumor size, and patient age are important prognostic factors. Other favorable factors included insurance and surgical management. The use of immunotherapy has increased over time and may improve survival in those with distant disease. These data support further investigation into the role of immunotherapy for vulvar melanoma to optimize outcomes.
Topics: Aged; Female; Humans; Medicare; Melanoma; Neoplasm Staging; Prognosis; Retrospective Studies; United States; Vulvar Neoplasms
PubMed: 32808496
DOI: 10.3802/jgo.2020.31.e66 -
Bladder Cancer (Amsterdam, Netherlands) 2022Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the...
BACKGROUND
Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the small number of reports regarding this disease.
OBJECTIVE
To describe the clinical, pathological, and molecular characteristics of urethral melanoma.
METHODS
We summarized the clinicopathologic data for 31 patients treated for urethral melanoma from 1986-2017 at our institution. Genomic data from our institutional sequencing platform MSK-IMPACT ( = 5) and gene-specific PCR data on , , and/or ( = 8) were compared to genomic data of cutaneous melanomas ( = 143), vulvar/vaginal melanomas ( = 24), and primary non-melanoma urethral tumors ( = 5) from our institutional database.
RESULTS
Twenty-three patients were diagnosed with localized disease, 7 had regional/nodal involvement and one had metastases. Initial treatment included surgery in 25 patients; seven had multimodal treatment. Median follow-up was 46 months (IQR 33-123). Estimated 5-year cancer-specific survival was 45%. No significant change in survival was observed based on a year of treatment.Primary urethral melanomas showed a higher frequency of mutations compared to cutaneous (80.0% vs. 18.2%, = 0.006) and vulvar/vaginal melanomas (80.0 vs. 25.0%, = 0.04). mutations were absent in urethral primaries (0% vs. 46% in cutaneous melanoma, = 0.02). Tumor mutation burden was higher in cutaneous than urethral melanomas ( = 0.04). Urethral melanomas had a higher number of somatic alterations compared to non-melanoma urethral tumors (median 11 vs. 5, = 0.03).
CONCLUSIONS
Our findings support a unique mutational landscape of urethral melanoma compared to cutaneous melanoma. Survival remains poor and is unchanged over the time studied.
PubMed: 36277327
DOI: 10.3233/BLC-211633 -
Modern Pathology : An Official Journal... Dec 2022Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions,...
Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions, mutations, and copy number changes, were performed on 750 melanomas (375 primary and 375 metastases) at our institution from 2014-2021. These included 599 (80%) cutaneous, 38 (5%) acral, 11 (1.5%) anorectal, 23 (3%) sinonasal, 27 (3.6%) eye (uveal/ conjunctiva), 11 (1.5%) genital (vulva/penile), and 41 (5.5%) melanomas of unknown primary. Sixteen fusions (2%) were detected in samples from 16 patients: 12/599 (2%) cutaneous, 2/38 (5%) acral, 1/9 (11%) vulva, 1/23(4.3%) sinonasal; and 12/16 (75%) fusions were potentially targetable. We identified two novel rearrangements: NAGS::MAST2 and NOTCH1::GNB1; and two fusions that have been reported in other malignancies but not in melanoma: CANT1::ETV4 (prostate cancer) and CCDC6::RET (thyroid cancer). Additional fusions, previously reported in melanoma, included: EML4::ALK, MLPH::ALK, AGAP3::BRAF, AGK::BRAF, CDH3::BRAF, CCT8::BRAF, DIP2B::BRAF, EFNB1::RAF1, LRCH3::RAF1, MAP4::RAF1, RUFY1::RAF1, and ADCY2::TERT. Fusion positive melanomas harbored recurrent alterations in TERT and CDKN2A, among others. Gene fusions were exceedingly rare (0.2%) in BRAF/RAS/NF1-mutant tumors and were detected in 5.6% of triple wild-type melanomas. Interestingly, gene rearrangements were significantly enriched within the subset of triple wild-type melanomas that harbor TERT promoter mutations (18% versus 2%, p < 0.0001). Thirteen (81%) patients were treated with immunotherapy for metastatic disease or in the adjuvant setting. Six of 12 (50%) patients with potentially actionable fusions progressed on immunotherapy, and 3/6 (50%) were treated with targeted agents (ALK and MEK inhibitors), 2 off-label and 1 as part of a clinical trial. One patient with an AGAP3::BRAF fusion positive melanoma experienced a 30-month long response to trametinib. We show that, detecting fusions, especially in triple wild-type melanomas with TERT promoter mutations, may have a clinically significant impact in patients with advanced disease who have failed front-line immunotherapy.
Topics: Male; Female; Humans; Proto-Oncogene Proteins B-raf; Melanoma; Gene Fusion; Mutation; Receptor Protein-Tyrosine Kinases; Nerve Tissue Proteins
PubMed: 35871080
DOI: 10.1038/s41379-022-01138-z -
Biomedicines Jun 2021Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can... (Review)
Review
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.
PubMed: 34209084
DOI: 10.3390/biomedicines9070758 -
Melanoma Research Aug 2023Malignant vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of rare malignant melanomas with critical biological properties that differ from... (Observational Study)
Observational Study
Malignant vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of rare malignant melanomas with critical biological properties that differ from other cancers. In Japan, adequate surveys have yet to be conducted. This study aimed to elucidate the clinicopathological demographics and outcomes of VuM and VaM in Japan. This retrospective observational study included women with invasive VuM or VaM identified from older medical records in Japan. We collected clinical data and used the Kaplan-Meier method to analyze progression-free survival (PFS) and overall survival (OS). Univariate and multivariate regression models were used to identify factors significantly related to survival. We identified 217 patients, 109 (50.2%) with VuM and 108 (49.8%) with VaM. The median PFS was 16.8 months in patients with VuM [95% confidence interval (CI), 23.1-87.7] and 15.6 months in those with VaM (95% CI, 8.4-12.6). The median OS was 43.9 months (95% CI, 60-138) and 31.1 months (95% CI, 24.8-45.3) in patients with VuM and VaM, respectively. Multivariate analysis showed that a disease stage higher than stage III, based on the American Joint Committee on Cancer (AJCC) guidelines, was associated with poorer PFS [hazard ratio (HR), 2.063; 95% CI, 0.995-4.278] and an unknown surgical margin was the only independent factor influencing OS (HR, 2.188; 95% CI, 1.203-3.977). The overall outcomes of invasive VuM and VaM in Japan remain poor. AJCC staging and surgical margins were significant predictors of survival.
Topics: Humans; Female; Melanoma; Skin Neoplasms; Japan; Vaginal Neoplasms; Vulvar Neoplasms; Vagina; Vulva; Demography; Retrospective Studies; Neoplasm Staging; Prognosis; Melanoma, Cutaneous Malignant
PubMed: 37162526
DOI: 10.1097/CMR.0000000000000894 -
Journal of the National Comprehensive... Mar 2024Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to...
Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.
Topics: Female; Humans; Adenocarcinoma; Genital Neoplasms, Female; Paget Disease, Extramammary; Skin Neoplasms; Vulvar Neoplasms
PubMed: 38503056
DOI: 10.6004/jnccn.2024.0013 -
Age and Ageing May 2023previous studies have focused on the risk of cardiovascular disease (CVD)-related death in individual cancers, adolescents or all cancers.
BACKGROUND
previous studies have focused on the risk of cardiovascular disease (CVD)-related death in individual cancers, adolescents or all cancers.
OBJECTIVE
to evaluate the risk of CVD-related death in older patients with cancer.
METHODS
older patients with cancer (over 65 years) of 16 cancers diagnosed between 1975 and 2018 were screened out from the Surveillance, Epidemiology and End Results program. The proportion of deaths, competing risk regression models, standardized mortality ratios (SMRs) and absolute excess risks (AERs) were used to assess the risk of CVD-related death.
RESULTS
this study included 1,141,675 older patients (median follow-up: 13.5 years). Of the 16 individual cancers, the risk of CVD death exceeded primary neoplasm death in older patients with cancers of the breast, endometrium, vulva, prostate gland, penis and melanoma of the skin over time (high competing risk group). Compared to the general older population, older patients with cancer had higher SMR and AER of CVD-related death (SMR: 1.58-4.23; AER: 21.16-365.89), heart disease-related death (SMR: 1.14-4.16; AER: 16.29-301.68) and cerebrovascular disease-related death (SMR: 1.11-4.66; AER: 3.02-72.43), with the SMR trend varying with CVD-related death competing risk classifications. The risk of CVD-related death in the high-competing risk group was higher than in the low-competing risk group.
CONCLUSIONS
for older patients with cancer, six of 16 individual cancers, including breast, endometrium, vulva, prostate gland, penis and melanoma of the skin was at high risk of CVD-related death. Management for long-term cardiovascular risk in older patients with cancer is needed.
Topics: Male; Female; Humans; Adolescent; Aged; Cause of Death; Cardiovascular Diseases; Heart Diseases; Risk Factors; Melanoma
PubMed: 37192506
DOI: 10.1093/ageing/afad068 -
Journal of Lower Genital Tract Disease Jan 2023Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they...
OBJECTIVES
Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they have impacted cancer treatment, an understanding of recent innovations in the molecular features of vulvar lesions is important.
MATERIALS AND METHODS
Systematic literature search was performed on PubMed, Google Scholar, and Scopus databases for molecular and genetic characteristics of vulvar neoplasms. Peer-reviewed literature published in English is included.
RESULTS
Squamous cell carcinoma (SCC) and its precursors are the predominant neoplasm at this site. Human papillomavirus (HPV) plays a crucial role in the pathogenesis of some of these lesions. Human papillomavirus-associated SCC follows the carcinogenic pathway driven by viral proteins E6 and E7 while HPV-independent SCC shows a high incidence of mutation of TP53 and CDKN2A genes. Mutations in the genes involving the PI3K-Akt pathway play an important role in the pathogenesis of both types of SCC. Among other vulvar malignancies, melanoma, and vulvar Paget disease (VPD) pose a significant clinical challenge and have unique molecular characteristics. Compared with dermal cutaneous melanoma, vulvar melanoma shows a higher rate of mutation of cKIT and NRAS genes and a lower rate of mutations in BRAF . Less than 20% of VPD shows amplification of ERBB2 and seldom shows mutation in genes involving the PI3K-Akt pathway.
CONCLUSIONS
Several potentially targetable molecular pathways have emerged as they have been shown to be involved in the tumorigenesis of SCC, melanoma, and VPD.
Topics: Female; Humans; Carcinoma, Squamous Cell; Human Papillomavirus Viruses; Melanoma; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Skin Neoplasms; Vulvar Neoplasms
PubMed: 36083687
DOI: 10.1097/LGT.0000000000000701