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.

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 (S100β), 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.

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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.

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.
METHODS: 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.
CONCLUSIONS: 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.

UNASSIGNED: 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.
UNASSIGNED: The authors present a patient with primary right intranasal melanotic mucosal melanoma.
UNASSIGNED: An endoscopic medial maxillectomy was done, and the patient was linked to the oncology department for radiotherapy.

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.

Acral and mucosal melanoma are uncommon variants of melanoma. Acral melanoma has an age-adjusted incidence of approximately 1.8 cases per million individuals per year, accounting for about 2% to 3% of all melanoma cases. On the other hand, mucosal melanoma, with an incidence of 2.2 cases per million per year, makes up around 1.3% of all melanoma cases. These melanomas, in addition to being biologically and clinically distinct from cutaneous melanoma, share certain clinical and pathologic characteristics. These include a more aggressive nature and a less favorable prognosis. Furthermore, they exhibit a different mutational pattern, with KIT mutations being more prevalent in acral and mucosal melanomas. This divergence in mutational patterns may partially account for the relatively poorer prognosis, particularly to immune checkpoint inhibitors. This review explores various aspects of acral and mucosal melanoma, including their clinical presentation, pathologic features, mutational profiles, current therapeutic approaches, outcomes associated with systemic therapy, and potential strategies to address resistance to existing treatments.

UNASSIGNED: Malignant melanoma most commonly occurs in the skin. Primary malignant melanoma of endometrium is quite rare. Its diagnosis depends on clinical characteristics and pathological examination. It usually exhibits high degree of tumor histology, early onset of distant metastases, and unfavorable prognoses.
UNASSIGNED: In this paper, we report a case of a 73-year-old woman with primary malignant melanoma of endometrium. This patient denied a history of nevus removal or any family medical history of cancer. She was admitted to the hospital for irregular vaginal bleeding after menopause and performed an endometrial biopsy. Pathological of the scrapings suggested malignant melanoma. She subsequently underwent a radical surgery. The final pathology diagnosis was primary malignant melanoma of endometrium, and BRAF gene mutation was detected. The tumor staged as IVB according to the International Federation of Gynecology and Obstetrics (FIGO) classification. Thus, she then started adjuvant chemotherapy. This patient is currently on oral targeted therapy and is still being followed up.
UNASSIGNED: Mucosal melanoma is infrequent, and primary malignant melanoma of endometrial is a rare subtype. To the best of our knowledge, malignant melanoma originating from endometrium has never been reported before. It has a high degree of malignancy and is prone to early metastasis. Further investigations are warranted to explore its underlying pathogenesis, management, and outcomes.

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.