Genetic Analysis of Melanoma Types Using Japanese Genomic Database.

OBJECTIVES: The purpose of this study is to compare genetic mutations, tumor mutation burden (TMB), and the effects of molecular targeted drugs and immune checkpoint inhibitors (ICIs) in head and neck mucosal melanoma (HNMUM) with those in skin melanoma (SKM) and ocular melanoma (OM). METHODS: Data were analyzed for 72 consecutive patients with HNMUM, including 366 with SKM and 31 with OM, registered at the Japan National Cancer Center, Center for Cancer Genomics and Advanced Therapeutics (C-CAT) between June 2019 and October 2023. Genetic alterations and TMB were determined by FoundationOne CDx next-generation sequencing. RESULTS: The top 10 mutations in HNMUM were RAD21 (47.2%), NBN (45.8%), MYC (40.3%), LYN (31.9%), NRAS (29.1%), IRF4 (23.6%), DAXX (22.2%), KIT (22.2%), NOTCH3 (20.8%), and DDR1 (19.4%), with 16.6 ± 0.8 (mean ± SEM) mutations/individual. In SKM, BRAF (p = 0.04) mutation was associated with a significantly better prognosis. The TMB values were 5.7 ± 2.1 (mean ± SEM) in HNMUM, 4.1 ± 0.2 in SKM, and 3.4 ± 0.9 in OM, with no significant differences among the three groups. The median survival time for patients with distant metastases was 803 (95% confidence interval: 539-NA) days for HNMUM, 1413 (831-2172) days for SKM, and 1138 (438-NA) days for OM. CONCLUSIONS: The top 10 mutations in HNMUM are closer to those in OM than those in SKM. There was no significant difference in TMB values or survival rates with regard to the therapeutic effect of ICIs among the diseases, which suggests that current treatment of HNMUM with ICIs is appropriate. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Adjuvant Therapy with Immune Checkpoint Inhibitors after Carbon Ion Radiotherapy for Mucosal Melanoma of the Head and Neck: A Case-Control Study.

The development of new treatment strategies to improve the prognosis of mucosal malignant melanoma of the head and neck (MMHN) after carbon ion radiotherapy (CIRT) is essential because of the risk of distant metastases. Therefore, our objective was to evaluate the outcomes of immune checkpoint inhibitor (ICI) treatment to justify its inclusion in the regimen after CIRT. Thirty-four patients who received CIRT as an initial treatment were included in the analysis and stratified into three groups: those who did not receive ICIs (Group A), those who received ICIs after recurrence or metastasis (Group B), and those who received ICIs as adjuvant therapy after CIRT (Group C). In total, 62% of the patients (n = 21) received ICIs. The 2-year local control and overall survival (OS) rates for all patients were 90.0% and 66.8%, respectively. The 2-year OS rates for patients in Groups A, B, and C were 50.8%, 66.7%, and 100%, respectively. No significant differences were observed between Groups A and B (p = 0.192) and Groups B and C (p = 0.112). However, a significant difference was confirmed between Groups A and C (p = 0.017). Adjuvant therapy following CIRT for MMHN may be a promising treatment modality that can extend patient survival.

Confocal Laser Endomicroscopy in Resection of Sinonasal Malignant Melanoma-Preliminary Report on Real-Time Margin Assessment and Support in Surgical Decision-Making.

Background/Objectives: Building upon the rising value of Confocal Laser Endomicroscopy (CLE) in squamous cell carcinoma of the head and neck, we present the first application of CLE during the resection of sinonasal malignant melanomas. This study aims to evaluate the potential of CLE to assist surgeons in intraoperative decision-making, with a particular focus on resection margin assessment within the constrained nasal cavity. Methods: Two cases of sinonasal malignant melanoma were included in this study. CLE was employed to examine visible tumors and their margins, both pre- and post-endoscopic resection. The findings were compared to histopathological results as well as data on squamous cell carcinoma, for which malignancy criteria had already been established in prior projects. Results: CLE provided the real-time visualization of sinonasal malignant melanomas and their margins, successfully differentiating between healthy and neoplastic tissue compared to histopathological findings. Conclusion: CLE offers the potential for real-time assessment, aiding surgeons in more precise tumor resection and potentially improving patient outcomes. This study demonstrates the feasibility of using CLE in the resection of sinonasal malignant melanoma, highlighting its ability to differentiate between healthy and neoplastic tissue intraoperatively.

Impact of Treatment Delay in Head and Neck Mucosal Melanoma on Overall Patient Survival.

Objectives Head and neck mucosal melanoma (HNMM) is a rare malignancy with high mortality. This study evaluates the impact of treatment delays on overall survival in HNMM. Design/Setting/Participants A retrospective review of patients with surgically managed HNMM treated with adjuvant radiation was performed from the 2004-2016 National Cancer Database. Main Outcome Measures Durations of diagnosis-to-treatment initiation (DTI), surgery-to-radiotherapy initiation (SRT), duration of radiotherapy (RTD), surgery-to-immunotherapy initiation (SIT), diagnosis-to-treatment end (DTE), and total treatment package (TTP) were calculated. Results A total of 1,011 patients (50.7% female, 90.5% Caucasian) met inclusion criteria. Median DTI, SRT, RTD, SIT, DTE, and TTP were 30, 49, 41, 102, 119, and 87 days, respectively. Only longer DTE was associated with decreased mortality (hazard ratio, 0.720; 95% confidence interval, 0.536-0.965; p = 0.028). Conclusion DTI, SRT, RTD, SIT, and TTP do not significantly affect overall survival in patients with HNMM who undergo surgery and adjuvant radiation. Longer DTE is associated with improved survival in this population. Level of Evidence 4.

Clinical Characteristics and Special Considerations in the Management of Rare Melanoma Subtypes.

Rare histologic subtypes of melanoma, including acral, mucosal, uveal, and desmoplastic melanomas, only make up 5% of all diagnosed melanomas and are often underrepresented in large, randomized trials. Recent advancements in systemic therapy have shown marked improvement in pathologic response rates, improving progression-free and overall survival among cutaneous melanoma patients, but there are limited data to demonstrate improved survival among rarer subtypes of melanoma. Acral melanoma has a poor response to immunotherapy and is associated with worse survival. Mucosal melanoma has a large variability in its presentation, a poor prognosis, and a low mutational burden. Uveal melanoma is associated with a high rate of liver metastasis; recent adoption of infusion and perfusion therapies has demonstrated improved survival among these patients. Desmoplastic melanoma, a high-risk cutaneous melanoma, is associated with high locoregional recurrence rates and mutational burden, suggesting this melanoma may have enhanced response to immunotherapy. While these variants of melanoma represent distinct disease entities, this review highlights the clinicopathologic characteristics and treatment recommendations for each of these rare melanomas and highlights the utility of modern therapies for each of them.

Survival of patients with mucosal melanoma in Cali, Colombia: a retrospective cohort study.

BACKGROUND: Mucosa melanoma is a rare condition with aggressive behavior and a less favorable prognosis compared to cutaneous melanoma. The objective of this study was to estimate the overall survival and clinical outcomes of patients diagnosed with mucosal melanoma in a Colombian hospital. METHODS: A retrospective cohort study was conducted at Fundación Valle del Lili, a single center located in Cali, Colombia. Patients aged ≥ 18 years, both sexes, diagnosed with mucosal melanoma by histopathology study were included between 2010-2019. Patients who received extra-institutional treatment or whose vital status was unknown during follow-up were excluded. Demographic, clinical and laboratory data were obtained from medical records and laboratory and pathology databases. A descriptive analysis was performed. Survival analysis was conducted using the Kaplan-Meier method. RESULTS: A total of 23 patients were included. Median age was 63 years old (IQR: 57-68) and 52.2% were woman. Clinical stage was 34.8% early, 26.1% locally advanced and 39.1% metastatic. The main primary locations were nasopharynx (30.4%), genitals (26.1%), rectum (21.7%), oral cavity (13%) and paranasal sinuses (8.7%). The majority received surgery (30.4%) and immunotherapy (26.1%) as first line treatment. Overall survival at one year was 80.8%, at three years 44.3%, and at five years 36.9%. CONCLUSION: Mucosal melanoma is a rare, aggressive disease with adverse oncological outcomes due to late diagnosis and limited treatment options. This study provides real-world data in a single-center of Colombia.

Survival and Treatment Modalities in Primary Vaginal Melanoma-Case Report and a Narrative Review.

Background/Objectives: Primary vaginal melanoma (PVM) is a rare cancer representing five percent of vaginal cancers and less than one percent of all female vaginal melanomas, with an incidence rate of 0.46 per million women per year. The aim of this study was to present a case of combined therapy and conservative surgical treatment in a young patient with PVM and to perform a systematic review of the same subject. Methods: We performed a narrative review of the literature and presented a case report. Results: The review yielded a total of 43 articles. We presented treatment modalities and survival outcomes. The presented case involved a combination of surgical treatment with adjuvant therapy comprising nivolumab and ipilimumab. Conclusions: PVM is a disease with a poor prognosis; however, new treatment options are promising and have a great chance of significantly improving survival. The combination of the wide local excision of the primary lesion followed by adjuvant therapies results in the best outcomes in the treatment of PVM. Future clinical studies are warranted to provide new evidence for the treatment outcomes of nonsurgical, metastatic PVM and the adjuvant treatment of PVM.

A Rare Case of Invasive Malignant Melanoma Metastasis in the Vulvar Mucosa 11 Years After Diagnosis and Treatment.

Mucosal melanoma is rare and the occurrence of an invasive malignant melanoma metastasis 11 years post-initial diagnosis is equally uncommon. This is a case of a 66-year-old woman with a history of bilateral vulvar invasive melanoma, who presented with an enlarging inguinal mass with associated tenderness upon palpation. After a right inguinal excisional lymph node biopsy, the pathological findings determined the final diagnosis as metastatic melanoma. To the best of our knowledge, this is the first report of vulvar mucosal melanoma metastasis greater than 10 years after initial diagnosis and treatment in the English language. This case discusses how treatment options for metastatic mucosal melanoma pose a challenge in such cases where follow-up for medical care is lacking. It also highlights the need for further preventative techniques and research directed towards screening techniques, staging guidelines, and treatment options for mucosal melanoma.

Establishment of Canine Oral Mucosal Melanoma Cell Lines and Their Xenogeneic Animal Models.

Canine oral melanoma is the most prevalent malignant tumor in dogs and has a poor prognosis due to its high aggressiveness and high metastasis and recurrence rates. More research is needed into its treatment and to understand its pathogenic factors. In this study, we isolated a canine oral mucosal melanoma (COMM) cell line designated as COMM6605, which has now been stably passaged for more than 100 generations, with a successful monoclonal assay and a cell multiplication time of 22.2 h. G-banded karyotype analysis of the COMM6605 cell line revealed an abnormal chromosome count ranging from 45 to 74, with the identification of a double-armed chromosome as the characteristic marker chromosome of this cell line. The oral intralingual and dorsal subcutaneous implantation models of BALB/c-nu mice were successfully established; Melan-A (MLANA), S100 beta protein (S100ß), PNL2, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2) were stably expressed positively in the canine oral tumor sections, tumor cell lines, and tumor sections of tumor-bearing mice. Sublines COMM6605-Luc-EGFP and COMM6605-Cherry were established through lentiviral transfection, with COMM6605-Luc-EGFP co-expressing firefly luciferase (Luc) and enhanced green fluorescent protein (EGFP) and COMM6605-Cherry expressing the Cherry fluorescent protein gene. The COMM6605-Luc-EGFP fluorescent cell subline was injected via the tail vein and caused lung and lymph node metastasis, as detected by mouse live imaging, which can be used as an animal model to simulate the latter steps of hematogenous spread during tumor metastasis. The canine oral melanoma cell line COMM6605 and two sublines isolated and characterized in this study can offer a valuable model for studying mucosal melanoma.

Endoscopic ultrasound features of rectal melanoma: A case report and review of literature.

BACKGROUND: Rectal mucosal melanoma is a rare and highly aggressive disease. Common symptoms include anal pain, an anal mass, or bleeding. As such, the disease is usually detected on rectal examination of patients with other suspected anorectal diseases. However, due to its rarity and nonspecific symptoms, melanoma of the rectal mucosa is easily misdiagnosed. CASE SUMMARY: This report describes the case of a 58-year-old female patient who presented with a history of blood in her stool for the prior one or two months, without any identifiable cause. During colonoscopy, a bulge of approximately 2.2 cm × 2.0 cm was identified. Subsequently, the patient underwent endoscopic ultrasound (EUS) to characterize the depth of invasion of the lesions. EUS suggested a hypoechoic mucosal mass with involvement of the submucosal layer and heterogeneity of the internal echoes. Following surgical intervention, the excised tissue samples were examined and confirmed to be rectal malignant melanoma. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: This case shows that colonoscopy with EUS and pathological examination can accurately diagnose rare cases of rectal mucosal melanoma.

[About a case of primary laryngeal mucosal melanoma in a patient with medical history of oropharyngeal squamous carcinoma]. / À propos d'un cas de mélanome muqueux primitif laryngé chez un patient présentant un antécédent de carcinome épidermoïde de l'oropharynx.

INTRODUCTION: Primary laryngeal mucosal melanoma is a rare tumour with a poor prognosis. Its often difficult diagnosis should rule out laryngeal metastatic localization of cutaneous melanoma. CASE PRESENTATION: We report a case of primary laryngeal mucosal melanoma diagnosed in a 65-year-old man, treated 6 years previously with radio-chemotherapy and surgery for squamous cell carcinoma of the right lateral oropharyngeal region. The definitive diagnosis of primary laryngeal mucosal melanoma was made on the resection specimen, whereas the initial biopsy of the epilaryngeal mass discovered during the patient's surveillance had concluded that it was a laryngeal recurrence of the known squamous cell carcinoma. DISCUSSION: Through this case, we propose to remind the main characteristics and the diagnostic pitfalls of these tumours.

Outcomes of Immunotherapy in Sinonasal Mucosal Melanoma Patients With Recurrent and Metastatic Disease.

Sinonasal mucosal melanoma (SNMM) is a rare malignancy with poor prognosis and high recurrence rate. In those with recurrence, survival is dismal. Immunotherapy is an emerging area of investigation; however, there is a scarcity of data on immunotherapy outcomes in SNMM patients with recurrence. We report outcomes of immunotherapy in recurrent SNMM patients with distant versus nondistant recurrence. Fifty-four patients with recurrent SNMM were identified, and 31 (57.4%) had distant recurrence. One-year overall survival (OS) following recurrence was 47.5% (95% confidence interval [CI]: 34.0%-60.9%), with a median survival of 2.8 years (95% CI: 2.0-5.3). In those with distant recurrence, receipt of immunotherapy was associated with better OS compared to those without immunotherapy (hazard ratio [HR] = 0.29 [95% CI: 0.12-0.68], P = .004). While patients with nondistant recurrence (n = 23), who received immunotherapy (n = 6) had worse OS compared to those who did not receive immunotherapy (HR = 4.76 [95% CI: 1.36, 15.89], P = .02). LEVEL OF EVIDENCE: Level IV.

Case report: Durable complete response of a mucosal melanoma of the rectum after neoadjuvant immunotherapy with ipilimumab plus nivolumab.

Melanoma causes the majority of skin cancer-related deaths. Despite novel therapy options, metastatic melanoma still has a poor prognosis. Immune checkpoint inhibition (ICI) therapy has been shown to prolong overall survival in patients with advanced melanoma, but mucosal melanomas respond less favorably compared to melanomas of cutaneous origin. We report on a patient with a mucosal melanoma of the rectum diagnosed in June 2020. Since a surgical intervention in order to achieve a tumor-free situation would have required an amputation of the rectum, a neo-adjuvant systemic immunotherapy with ipilimumab and nivolumab was initiated. As restaging and colonoscopy after four doses of this combination immunotherapy showed a partial response, the patient decided against the pre-planned surgery and a maintenance therapy with nivolumab was started. Repeated colonoscopy showed a complete response after four doses of nivolumab. After ongoing ICI therapy with nivolumab and no evidence of tumor relapse, immunotherapy was stopped in July 2022 after nearly 2 years of continuous treatment. The patient remained tumor-free during further follow-up. Neo-adjuvant immunotherapy is getting more explored in advanced melanoma. By administering ICI therapy before surgical resection of an essentially operable tumor, a stronger and more diverse immunological response is supposed to be achieved. Our reported case demonstrates that this approach could also be effective in mucosal melanoma despite of its generally lower response to immunotherapy.

Sinonasal mucosal melanoma in The Netherlands between 2001 and 2021: a clinical and epidemiological overview of 320 cases.

PURPOSE: Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced. METHODS: All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR). RESULTS: A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only - 0.01%. The 5-year overall survival (OS) and relative survival (RS) were 24.5 and 32.4%, respectively. Relative survival did not increase over time. The addition of adjuvant radiotherapy to surgery was not associated with a higher OS and RS compared to surgery alone. CONCLUSION: Sinonasal mucosal melanoma is a rare disease with stable incidence rates in the Netherlands between 2001 and 2021. There has been no improvement in survival over the course of the inclusion period. The study reaffirms that adjuvant radiotherapy does not seem to improve patient outcomes. Given the generally poor outcomes for SNMM patients, novel therapeutic options ought to be considered in order to improve care.

The efficacy and safety of dalpiciclib, a cyclin-dependent kinase 4/6 inhibitor, in patients with advanced head and neck mucosal melanoma harboring CDK4 amplification.

BACKGROUND: Mucosal melanoma (MM) is a rare but devastating subtype of melanoma. Our previous studies have demonstrated robust anti-tumor effects of cyclin-dependent kinase 4/6 (CDK 4/6) inhibitors in head and neck MM (HNMM) patient-derived xenograft models with CDK4 amplification. Herein, we aimed to investigate the efficacy and safety of dalpiciclib (SHR6390), a CDK4/6 inhibitor, in HNMM patients harboring CDK4 amplification. METHODS: The anti-tumor efficacy of dalpiciclib was assessed by HNMM patient-derived xenograft (PDX) models and patient-derived tumor cells (PDC) in vivo and in vitro. Immunohistochemical analyses and western blot were then performed to assess the markers of cell proliferation and CDK4/6 signaling pathway. For the clinical trial, advanced recurrent and/or metastatic HNMM patients with CDK4 amplification were treated with dalpiciclib 125 mg once daily for 21 consecutive days in 28-day cycles. The primary endpoint was disease control rate (DCR). Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: Dalpiciclib profoundly suppressed growth of HNMM-PDX and PDC with CDK4 amplification, whereas it showed relatively weak suppression in those with CDK4 wild type compared with vehicle. And dalpiciclib resulted in a remarkable reduction in the expression levels of Ki-67 and phosphorylated Rb compared with control group. In the clinical trial, a total of 17 patients were enrolled, and 16 patients were evaluable. The ORR was 6.3%, and the DCR was 81.3%. The estimated median PFS was 9.9 months (95% CI, 4.8-NA), and the median OS was not reached. The rate of OS at 12 months and 24 months was 68.8% (95% CI, 0.494-0.957) and 51.6% (95% CI, 0.307-0.866), respectively. The most frequent adverse events were neutrophil count decrease, white blood cell count decrease, and fatigue. CONCLUSIONS: Dalpiciclib was well-tolerated and displayed a durable benefit for HNMM patients with CDK4 amplification in this study. Further studies on CDK4 inhibitors and its combination strategy for MM are worth further exploration. TRIAL REGISTRATION: ChiCTR2000031608.

Local intralesional talimogene laherparepvec therapy with complete local response in oral palatine mucosal melanoma: a case report.

BACKGROUND: Mucosal melanoma, an aggressive type of malignancy different from the cutaneous melanomas commonly seen in the head and neck region, represents < 1% of all malignant melanomas. The pathogenesis of mucosal melanoma is unknown. Targetable mutations commonly seen in cutaneous melanoma, such as in the BRAF and NRAS genes, have a lower incidence in mucosal melanoma. Mucosal melanoma carries a distinct mutational pattern from cutaneous melanoma. Surgery with negative margins is the first-line treatment for mucosal melanoma, and systemic therapy is not well defined. Talimogene laherparepvec, an oncolytic viral immunotherapy, is United States Food and Drug Administration approved for the treatment of advanced malignant cutaneous melanoma, with local therapeutic benefits. Mucosal melanoma was initially excluded from talimogene laherparepvec's initial phase III clinical trial. CASE PRESENTATION: We present the case of a white female patient in her 40s with past medical history of systemic lupus erythematous, scleroderma, and estrogen-receptor-positive invasive ductal breast carcinoma. Following a bilateral mastectomy, the patient was found to have BRAF-negative mucosal melanoma of her hard palate with a soft palate skip lesion. Owing to the presence of a skip mucosal lesion as well as the anticipated defect and need for free-flap reconstructive surgery, nonsurgical management was considered. The patient was referred to medical oncology, where-based on the patient's complicated medical history and the risk of immunotherapy possibly worsening her prior autoimmune diseases-local talimogene laherparepvec injections were chosen as the primary therapy for her mucosal lesions. Though talimogene laherparepvec is approved for the treatment of cutaneous melanoma, there are limited data available on the use of talimogene laherparepvec in mucosal melanomas. CONCLUSION: The patient had a complete local tumor response at both the primary lesion as well as the skip lesion with the local injections. She had no side effects and maintained a high quality of life during treatment.

Immunohistochemical and transcriptomic characterization of T and myeloid cell infiltrates in canine malignant melanoma.

Immune checkpoint inhibitor therapy can provide significant clinical benefit in patients with certain cancer types including melanoma; however, objective responses are only observed for a subset of patients. Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and, compared with cutaneous melanoma, is significantly less responsive to immune checkpoint inhibitors. Spontaneous canine tumours have emerged as valuable models to inform human cancer studies. In contrast to human melanoma, most canine melanomas are mucosal-an incidence that may be leveraged to better understand the subtype in humans. However, a more comprehensive understanding of the immune landscape of the canine disease is required. Here, we quantify tumour infiltrative T and myeloid cells in canine mucosal (n = 13) and cutaneous (n = 5) melanomas using immunohistochemical analysis of CD3 and MAC387 expression, respectively. Gene expression analysis using the Canine IO NanoString panel was also performed to identify genes and pathways associated with immune cell infiltration. T and myeloid cell densities were variable with geometric means of 158.7 cells/mm2 and 166.7 cells/mm2, respectively. Elevated T cell infiltration was associated with increased expression of cytolytic genes as well as genes encoding the coinhibitory checkpoint molecules PD-1, CTLA-4, TIM-3 and TIGIT; whereas increased myeloid cell infiltration was associated with elevated expression of protumourigenic cytokines. These data provide a basic characterization of the tumour microenvironment of canine malignant melanoma and suggest that, like human melanoma, inherent variability in anti-tumour T cell responses exists and that a subset of canine melanomas may respond better to immunomodulation.

Primary Intranasal Melanotic Mucosal Melanoma - A Case Report and Literature Review.

Background: Intranasal mucosal melanoma is a rare form of melanoma. Presenting as the features of occult malignancy and rapid in its progression. Presented with nonspecific symptoms. So far, no specific risk factor has been identified. The histopathological and immunohistochemical examination helps to confirm the diagnosis. Here, we present a case of primary intranasal melanotic mucosal melanoma and literature review. Case Report: The authors present a patient with primary right intranasal melanotic mucosal melanoma. Conclusion: An endoscopic medial maxillectomy was done, and the patient was linked to the oncology department for radiotherapy.

Primary malignant melanoma of the genitourinary tract: case series of a rare form of primary mucosal melanoma.

Primary malignant melanoma of the genitourinary tract is extremely rare. We present two such cases in elderly Caucasian females. An 81-year-old female with urinary retention and polypoid urinary bladder mass and a 72-year-old female with gross hematuria and urethral caruncle. After thorough evaluation, they were both eventually diagnosed with primary urogenital melanoma (SOX10 and MART1-positive in tumor cells). In both cases, the presence of melanoma-in-situ and absence of primary melanoma in other sites were consistent with primary urogenital melanoma. Immunotherapy with PD-1 inhibitors and use of neoadjuvant and adjuvant treatment are promising, as treatment guidelines remain unclear and overall survival is low. Additional clinical reporting of primary urogenital melanomas can help in better understanding and ultimately treating it.

Primary melanomas of the bladder and urinary tract are rare and usually deadly. They represent only 0.2% of all melanomas, including melanomas of skin. They can be difficult to diagnose and treat due to how rare they are and the lack of clear treatment guidelines. We present two cases of elderly Caucasian women who were unexpectedly diagnosed with primary melanoma cancers of the bladder and urinary tract after having surgery and analyzing tissue that was removed. Both tissue samples had features specific to melanoma and there was no cancer in any other organ, thus making them primary melanomas of the bladder and urinary tract. Current treatment approaches with surgery and chemotherapy have not improved the survival outcomes and prognosis associated with this disease, but treatment before and after surgery as well as cancer treatments that harness the person's own immune system are promising. By reporting additional clinical experiences of this often fatal disease, we hope it can be better understood and appropriately managed in the future.