Melanoma Research

Synchronous double primary vulvar melanoma: a not so rare possibility. A clinical and dermoscopic case study

Vulvar melanoma is considered rare, but it is the second most frequent vulvar neoplasm; 2% of melanomas in women arise in the vulvar area. It is important to highlight how the characteristics of vulvar melanoma differentiate it from classic cutaneous melanoma. Vulvar melanoma has different risk factors and clinical and dermoscopic characteristics; moreover, it has a higher recurrence rate and a greater likelihood of multifocality. Here, we present a case of a 44-year-old patient with two primary vulvar melanomas located on opposite sides of her vulva. The lesions were both flat, but they had distinct clinical and dermoscopic appearances. Melanoma of the genital tract is likely the result of a multifocal disorder of the melanocytes within the mucosa that inhabit the perineal squamous epithelium. The risk factors of vulvar melanoma differ from those of classical cutaneous melanomas. Vulvar melanoma occurs in an area shielded from ultraviolet radiation; the primary risk factors include chronic inflammatory disease, genetic susceptibility, irritant agents and viral infections. This case study reveals how a close examination of the genital area is important and how dermoscopy can aid in the differential diagnosis of vulvar lesions. Inspections of the genital area should be particularly thorough if a melanoma is detected there, given the higher risk of multifocality in that part of the body.

Immunotherapy for treatment of female genital tract melanoma: National Cancer Database analysis

Goal of this study was to examine the impact of immunotherapy on overall survival (OS) in patients with female genital tract melanoma (GTM). This retrospective cohort study utilized the National Cancer Database to identify individuals with invasive vulvar or vaginal melanoma diagnosed between 2004 and 2019. Kaplan–Meier plots and multivariate Cox regression were used to describe the impact of immunotherapy on OS and to examine predictors of OS among those who received immunotherapy for those with vulvar or vaginal melanoma. Of the 870 patients with vaginal melanoma, 23.6% received immunotherapy. Receiving immunotherapy for treatment of vaginal melanoma was associated with improved OS (median: 21.8 versus 18.9 months; P = 0.01); this association remained after adjustment for other prognostic factors [hazard ratio (HR), 0.77; 95% confidence interval (CI), 0.62–0.95; P = 0.01]. The survival advantage was more pronounced among those who did not receive primary surgical resection (median: 18.6 versus 12.2 months; P = 0.0009). Among 3123 patients with vulvar melanoma, 15.3% received immunotherapy. Receiving immunotherapy for treatment of vulvar melanoma was associated with an improvement in OS (median: 43.6 versus 57.7 months; P = 0.06; HR, 0.86; 95% CI, 0.74–1.00; P = 0.04). Survival benefit was more pronounced when restricted to patients with advanced or unknown stage disease (median OS, 31.6 versus 24.2 months; P = 0.002; adjusted HR, 0.74; 95% CI, 0.61–0.89; P = 0.002) and among the small subset who did not receive primary surgical resection (median: 19.8 versus 9.6 months; P = 0.0005). Immunotherapy was associated with improved OS in patients with female GTM, with some subsets particularly benefitting.

Late peritoneal carcinomatosis from cutaneous melanoma mimicking ovarian cancer

Peritoneal carcinomatosis represents an exceptionally rare metastatic pattern of cutaneous malignant melanoma, occurring in fewer than 1% of cases with distant spread and typically within the first few years after primary treatment. This report presents an unusual case with a markedly prolonged disease-free interval, clinically mimicking advanced ovarian carcinoma. We report the case of a 53-year-old woman treated more than 10 years ago for stage IIB nodular melanoma with surgery and adjuvant therapy. The patient presented with progressive abdominal bloating. Imaging revealed bilateral adnexal masses, ascites, peritoneal carcinomatosis, and multiple pulmonary nodules, initially suggestive of advanced ovarian cancer. Diagnostic laparoscopy demonstrated diffuse peritoneal lesions with an atypical yellowish, soft, and nonpigmented appearance. Histology and immunohistochemistry confirmed metastatic melanoma. This case is among the few reports of peritoneal carcinomatosis from melanoma after more than a decade of remission. The prolonged disease-free interval and atypical presentation underline the heterogeneous behavior of melanoma and the need for long-term vigilance and multidisciplinary evaluation.

Clinical features of vulvar and vaginal malignant melanomas and the effects of immune checkpoint inhibitors in Japanese patients: a single-center, retrospective cohort study

Vulvar and vaginal melanomas (VVMs) are rare malignancies, but they are relatively more common among Asian women. This makes the collection of data on VVMs in this population crucial. Moreover, no cohort studies have examined and compared the effects of immune checkpoint inhibitors (ICIs) on VVM in Asian women. Therefore, we aimed to investigate the clinical characteristics of VVMs in Japanese women and the effects of ICI treatment. This single-center, retrospective cohort study included patients who were histologically diagnosed with VVM at our hospital between March 2005 and December 2023. The Kaplan–Meier analysis was used to compare the prognosis of vulvar melanoma (VuM) and vaginal melanoma (VaM) throughout entire treatments and compare the efficacies of ICIs and conventional chemotherapies in VVM. In total, 28 women with VuM (n = 14) and VaM (n = 14) were included. There were no significant differences in overall survival (OS) [median OS: not reached (95% confidence interval (CI), 13.2–NA) vs. 30.2 months (95% CI, 23.2–NA), log-rank test, P = 0.456] between the VuM and VaM groups. The progression-free survival (median progression-free survival: 14.7 vs. 5.2 months, P = 0.002) and OS (median OS: 33.8 vs. 7.2 months, P < 0.001) were significantly better for the ICI-treated group than for the conventional chemotherapy-treated group in VVM. The prognosis of patients with VVM improved significantly with the advent of ICI, demonstrating the importance of ICI in the treatment of VVM.

Clinicopathological demographics of malignant melanomas of the vulva and vagina in Japan

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.

High-resolution RNA-sequencing reveals TRIM33::CSDE1 gene fusion in metastasizing vulvar melanoma

Although mucosal melanomas are rare and constitute approximately 1.4% of all melanomas, the prognosis of patients with mucosal melanoma is poorer in comparison to cutaneous melanomas. Despite their poor prognosis, limited treatment options are currently available for patients with advanced disease. These noncutaneous subtypes of melanomas are not responding to treatment used for cutaneous melanomas. We performed RNA sequencing on four mucosal melanoma samples comprising of two primary tumors and two corresponding metastases. A TRIM33::CSDE1 fusion was detected in both the primary tumor and metastasis of a vulvar melanoma, supporting the fusion to be a driver in oncogenesis. Vulvar melanoma is the third tumor to have been reported to harbor TRIM33::CSDE1 fusion. Detecting fusions may have a clinically significant impact in patients with advanced mucosal melanoma who have failed front-line immunotherapy.