Melanoma constitutes one of the most sinister and troublesome malignancies encountered by humanity. Generally, the diagnosis of advanced melanoma connotes a grave prognosis, prompting a sense of looming threat of death, however, the early-stage detected disease responds well to robust treatment resulting in reasonable survivorship. Scalp melanomas are even more troublesome, because they typically exhibit more aggressive biologic behavior and are often diagnosed at a late stage. This review tries to comprehensively highlight the various diagnostic, therapeutic, and outcome aspects of scalp melanomas. The literature research includes peer-reviewed articles (clinical trials or scientific reviews). Studies were identified by searching electronic databases (MEDLINE and PubMed) till May 2020 and reference lists of respective articles. Only articles published in English language were included.

Background: Mucosal melanomas (MM) arise within the lining of the gastrointestinal (GI), genitourinary (GU) and head and neck (HN) systems. Method: A retrospective analysis of the National Comprehensive Database identified 4,961 MM patients. Primary objective was to compare survival outcomes across the different locations. Results: Overall survival for GI melanomas was significantly shorter than HN and GU melanomas. Median survival (95% confidence interval) was 19.5 (18.0-21.5), 26.4 (24.9-28.3), and 43.9 (38.8-47.8), months for GI, HN and GU cases, respectively (p<0.0001). Conclusion: This is the largest study of MM in a US based population, demonstrating worse overall survival for GI MM in comparison to HN and GU melanomas.

BACKGROUND: Head and neck mucosal melanomas (MMs) are rare tumors with adverse outcomes and poorer prognoses than their more common cutaneous counterparts (cutaneous melanomas-CMs). Few studies have compared the expression of mitochondrial dynamic markers in these tumors. This study aimed to assess the correlations of mitochondrial markers with melanoma progression and their potential as predictors of lymph node involvement and distant metastasis.
METHODS: Immunohistochemistry against anti-mitochondrial (AMT), dynamin-related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), mitofusin-1 (MFN1), and mitofusin-2 (MFN2) antibodies was performed in 112 cases of head and neck CM and MM. A Cox regression multivariate model was used to assess the correlation of AMT, FIS1, and MFN2 expressions considering the risk for nodal and distant metastasis.
RESULTS: All markers studied presented higher staining in tumor cells than normal adjacent tissues. Higher mitochondrial content was observed in MM than in CM, and it was significantly associated with nodal metastasis in oral melanomas. Both FIS1 and DRP1 expressions were related to advanced Clark\'s levels in CM, and they were overexpressed in oral melanomas. Moreover, increased immunoexpression of MFN2 was significantly associated with a higher risk of metastasis in CM, and it was also overexpressed in sinonasal melanomas.
CONCLUSIONS: Our results suggest that mitochondrial fission and fusion processes can play an important role during multiple stages of tumorigenesis and the development of nodal and distant metastasis in cutaneous and mucosal melanomas.

Mitochondrial dysfunction is caused by an imbalance in the fission and fusion processes, and it has been implicated in the pathogenesis of several human cancers. However, the role of mitochondrial markers in melanomas still remains poorly understood. In this study, the authors assessed the expression of 3 mitochondrial markers (antimitochondrial, fission protein 1 [FIS1], and mitofusin 2 [MFN2]) in a series of head and neck mucosal and cutaneous melanomas. Patients with cutaneous (n = 56) and mucosal (oral, n = 30, sinonasal, n = 26) melanomas of the head and neck region were enrolled in this study. Clinical and follow-up data were retrieved from medical records. The expression of 3 mitochondrial markers was assessed by the immunohistochemistry, and then digitally quantified and correlated with clinicopathological data and outcome information. In the multivariate model, high mitochondrial content was identified as an independent prognostic value for disease-free survival (DFS) in cutaneous melanomas and overall survival in oral melanomas. FIS1 expression was significantly associated with lower overall survival rates in patients with oral melanomas and strictly correlated with vascular invasion in mucosal melanomas. MFN2 was associated with high risk of distant metastasis in patients with cutaneous melanomas. In summary, the authors demonstrated that mitochondrial content, along with FIS1 and MFN2 expressions, is correlated with important clinicopathological characteristics in patients with cutaneous and mucosal head and neck melanomas.