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Several studies have focused on identifying microRNAs involved in the pathogenesis of melanoma. However, its association with clinicopathological features has been scarcely addressed. The aim of this study is to identify microRNAs expression profiles related to aggressive clinicopathological and molecular features, and to analyze the association with melanoma survival. A retrospective and observational study was performed in a series of 179 formalin-fixed paraffin embedded primary cutaneous melanomas. First, a screening analysis on a discovery set (n = 22) using miRNA gene chip array (Affymetrix, Santa Clara, California, USA) was performed. Differentially expressed microRNAs were detected employing the software Partek Genomic Suite. Validation of four microRNAs was subsequently performed in the entire series (n = 179) by quantitative real time PCR (qRT-PCR). MicroRNAs expression screening analysis identified 101 microRNAs differentially expressed according to Breslow thickness (≤1 mm vs. >1 mm), 79 according to the presence or absence of ulceration, 78 according to mitosis/mm2 (<1 mitosis vs. ≥1 mitosis) and 97 according to the TERT promoter status (wt vs. mutated). Six microRNAs (miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p, miR-500a-5p, miR-339-5p) were selected for being validated by qRT-PCR in the discovery set (n = 22). Of those, miR-138-5p, miR-130b-3p, miR-30b-5p, miR-34a-5p were selected for further analysis in the entire series (n = 179). Overexpression of miR-138-5p and miR-130b-3p was significantly associated with greater Breslow thickness, ulceration, and mitosis. TERT mutated melanomas overexpressed miR-138-5p. Kaplan-Meier survival analysis showed poorer survival in melanomas with miR-130b-3p overexpression. Our findings provide support for the existence of a microRNA expression profile in melanomas with aggressive clinicopathological features and poor prognosis., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Melanocytic acral nevi have a series of distinguishing features, including their location, patient age at onset, clinical progression, and histological findings. In particular, histopathological analysis often reveals a melanocytic acral nevus with intraepidermal ascent of cells (MANIAC nevus), which in some cases can be mistaken for atypia or malignancy., Aim: This study describes the clinicopathological characteristics of acral nevi in patients under 18 years old and contrasts the clinical and histological features between MANIAC vs non-MANIAC nevi., Methods: This was a retrospective observational study, performed in our department in the decade between January 2007 and January 2017. We included patients younger than 18 years of age who were subjected to the removal of melanocytic acral nevi., Results: A total of 70 patients were studied. 54.2% (38/70) were females and 45.8% (32/70) were males. With regard to the type of nevus, 34 were compound, 27 were junctional, and 9 were predominantly intradermal lesions. We identified a total of 41 MANIAC nevi and 29 non-MANIAC nevi. Statistically significant differences between these two groups were identified in nevus size (larger in MANIAC) and the frequency of compound nevi (higher in the MANIAC group), but not in the remainder of the histological parameters studied., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Promoter methylation of tumour suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over 100 genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated., Objectives: This is a retrospective observational study that aims to analyse the prevalence of CpG island methylation in a series of primary melanomas, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival., Materials and Methods: DNA methylation was analysed using methylation-specific multiplex ligation-dependent probe amplification in a series of 170 melanoma formalin-fixed paraffin-embedded tumour samples. The relationship between the methylation status, known somatic mutations and clinicopathological features was evaluated. Disease-free survival (DFS) and overall survival (OS) were displayed by the Kaplan-Meier method., Results: In the entire cohort, one or more genes were detected to be methylated in 55% of the patients. The most prevalent methylated genes were RARB 31%, PTEN 24%, APC 16%, CDH13 16%, ESR1 14%, CDKN2A 6% and RASSF1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow thickness, presence of mitosis and ulceration, fast-growing melanomas, advancing stage and TERT mutations). Furthermore, Kaplan-Meier survival analysis showed a correlation of methylation and poorer DFS and OS., Conclusions: Aberrant methylation of TSGs is a frequent event in melanoma. It is associated with aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice., (© 2018 British Association of Dermatologists.)

Molecular diagnostics are increasingly performed routinely in the diagnosis and management of patients with melanoma due to the development of novel therapies that target specific genetic mutations. The development of next-generation sequencing (NGS) technologies has enabled to sequence multiple cancer-driving genes in a single assay, with improved sensitivity in mutation detection. The main objective of this study was the design and implementation of a melanoma-specific sequencing panel, and the identification of the spectrum of somatic mutations in a series of primary melanoma samples. A custom panel was designed to cover the coding regions of 35 melanoma-related genes. Panel average coverage was 2,575.5 reads per amplicon, with 92,8% of targeted bases covered ≥500×. Deep coverage enabled sensitive discovery of mutations in as low as 0.5% mutant allele frequency. Eighty-five percent (85/100) of the melanomas had at least one somatic mutation. The most prevalent mutated genes were BRAF (50%;50/199), NRAS (15%;15/100), PREX2 (14%;14/100), GRIN2A (13%;13/100), and ERBB4 (12%;12/100). Turn-around-time and costs for NGS-based analysis was reduced in comparison to conventional molecular approaches. The results of this study demonstrate the cost-effectiveness and feasibility of a custom-designed targeted NGS panel, and suggest the implementation of targeted NGS into daily routine practice.

Background: The prognostic value of sentinel lymph node (SLN) biopsy findings and mitotic activity in melanoma has been confirmed in the literature, but the relation between them has not been well established., Objectives: The main objective was to describe and analyze the correlation between SLN biopsy results and the mitotic rate in patients treated for melanoma in our hospital., Methods: A total of 139 consecutive patients who underwent SLN biopsy between May 2001 and May 2009 were included. The relation between the mitotic rate and SLN status was analyzed with the χ(2) test and the Fischer exact test., Results: The correlation between the 2 variables was nonsignificant (P =.071) in the patient series overall, but a significant association was found in the subgroup of patients with tumors of Breslow thickness between 1 and 4mm (P =.034). The likelihood (odds ratio) of SLN positivity with a mitotic rate of less than 1 mitosis/mm2 in this subgroup was 0.838 (95% CI, 0.758-0.926)., Conclusions: Our findings support use of the mitotic rate to predict SLN status in melanoma tumors of intermediate thickness. Our study also shows the need for further investigation of the relation between these 2 variables in thin and thick tumors., (Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.)

Intracranial invasion of cellular blue nevus is extremely rare, and its malignant transformation is even less common. The differential diagnosis includes neurocutaneous melanosis and neurocristic cutaneous hamartoma. A 50-year-old female presented with intracranial melanoma in contiguity with a congenital blue nevus on the scalp. The patient showed a wide pigmented lesion on the scalp that had grown in the last few years over the congenital blue nevus. Magnetic resonance imaging revealed an intracranial tumor lying contiguous to the nevus. Despite aggressive surgery, the tumor relapsed and the patient developed systemic metastases. We report a rare case of cellular blue nevus showing an unexpected aggressive behavior with extensive extra- and intracranial expansion and distant metastases.