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The aims of our study were to evaluate with ultra-highfrequency ultrasound (UHFUS) the ultrasound features of congenital melanocytic nevi (CMNs) and malignant melanomas (MMs) arising in CMNs and the correlation between ultrasonographic thickness and histological thickness in MMs. We evaluated 10 patients with smallmedium CMNs and 10 patients with MMs arising in small-medium CMNs. We collected patient's data, clinical and dermoscopic features. The UHFUS was performed using a 70 MHz frequency probe to study the ecostructure, shape and vascularization. Breslow thickness was compared with ultrasonographic thickness. In the MMs group the following dermoscopic features were described: hyperpigmentation (n = 9), regression area (n = 6), whitish-blue veil (n = 5), thickened network (n = 5), irregular globules (n = 3), inverse network (n = 2) and striae (n = 1). Hyperpigmentation (n = n = 9), thickened network (n = 7), irregular globules (n = 5), regression area (n = 5), striae (n = 1) and whitish-blue veil (n = 1) were found in the CMNs group. The multicomponent pattern was present in both MMs (n = 4) and in CMNs (n = 5). Moreover, the parameters indicative of suspected malignancy were variously combined in the two groups, without showing significant differences in the statistical analysis; with the exception of the blue veil that correlated with the diagnosis of MM. Ultrasonoghaphic vascularization was an ever-present parameter in MMs (100%), with high intensity of intratumoral signal, as opposed to CMNs. We also found a statistically significant correlation between ultrasound thickness and Breslow thickness. In the future, this technique could implement the diagnostic preoperative phase of MMs arising in CMNs in combination with standard clinical-dermatoscopic evaluation. Melanoma Res 31: 561

In Italy, few epidemiologic studies have been conducted by tracing melanoma reports directly in the electronic registers of the operating units of pathologic anatomy. The Cancer Registers of the Italian regions receive only partial and incomplete data on the diagnoses of melanoma, for this reason, the incidences are usually underestimated. Our work offers a precise picture of the epidemiologic situation of melanoma in a homogenous sample of patients residing in a geographic area traditionally considered to have a high incidence of melanoma.

Immune dysregulation, in combination with genetic and epigenetic alterations, induces an excessive proliferation of uncontrolled melanoma cells followed by dissemination of the tumor cells to distant sites, invading organs and creating metastasis. Although immunotherapy, checkpoint inhibitors and molecular targeted therapies have been developed as treatment options for advanced melanoma, there are specific mechanisms by which cancer cells can escape treatment. One of the main factors associated with reduced response to therapy is the ability of residual tumor cells to persist in a dormant state, without proliferation. This comprehensive review aimed at understanding the genetic basis of dormancy/awakening phenomenon in metastatic melanoma will help identify the possible therapeutical strategies that might eliminate melanoma circulating tumor cells (CTCs) or keep them in the dormant state forever, thereby repressing tumor relapse and metastatic spread.

Melanoma is the malignant tumor whose incidence increases with greater speed, in order to reduce mortality, primary prevention, early diagnosis, and correct therapies are essential. 1 Immune system and checkpoint blockers (ICI) (monoclonal antibodies targeted to the antigen-4 associated with cytotoxic T lymphocytes [CTLA-4], programmed cell death protein 1 [PD-1] or ligand of programmed death 1 [PD-L1]), have been increasingly used for their differential impact on the long-term survival of patients with metastatic melanoma. The usefulness of ICI therapy has been limited by immune-related adverse reactions, which affect systems of multiple organs. As reported by Chan et al. skin manifestations are

Pediatric melanoma is a rare form of the tumor whose epidemiology is widely increasing thanks to the improvement of dermoscopic and anatomopathologic diagnostic techniques. Although it is a tumor of considerable interest in adults, little has been described about the pediatric field. The objective of our study was then to identify the possible risk factors for the development of melanoma in the pediatric population. We performed a retrospective study conducted in the Melanoma and Skin Cancer Unit and Unit of Dermatology (Livorno, Italy). We analyzed a population of 38 children under 21 years with a diagnosis of melanoma. This population was compared with a control population of 114 children followed up in our dermatologic clinic. From our combined univariate-multivariate statistics analysis, the number of nevi [regression coefficient (RC) of 1.04 and odds ratio (OR) of 2.8 confidence interval (Cl, 1.2–6.6)], and family history of melanoma [RC of 1.99 and OR of 7.3 (Cl, 2.3–22.7)] emerged as possible risk factors for the development of melanoma. The identification of these elements would allow the physician to carry out a more targeted preliminary assessment of the patient, potentially decisive in cases of diagnostic doubt of the lesion. Our study also lays the foundations for identifying those children who, despite not having received a diagnosis of melanoma on histologic examination, should be considered as patients susceptible to a focused follow-up, because of the presence of the risk factors that emerged from our research.

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Objectives-The main aim of this study is to evaluate the correspondence between the ultrasonographic thickness and the Breslow thickness in melanoma using ultra-high frequency ultrasound and the intra-and inter-operator repeatability in the ultrasonographic measurements of melanoma depth. Moreover, we propose a new protocol based on a combined ultrasonographichistopathological approach.Methods-We analyzed 27 melanomas in a population consisted of 27 patients (mean age 57.6 years, 51.8% males), who came at the Department of Dermatology (University of Pisa, Pisa, Italy) from April 2016 to March 2018 and had an ultrasonographic examination of a suspected lesion before the surgical removal using ultra-high frequency ultrasound (Vevo ® MD, Fujifilm, Visualsonics, Toronto, Canada; 70 MHz probe). B-mode images were analyzed by two skilled and blinded operators, and the maximum depth of the lesions was measured using a dedicated graphical user interface developed in Matlab R2016b (MathWorks Inc., Natick, MA), to obtain repetitive measurements.Results-All melanomas appeared as band-like or oval/fusiform shaped hypoechoic inhomogeneous lesions. We observed an excellent agreement between the Breslow thickness of melanomas and the ultrasonographic thickness, as well as a reduced intra-and inter-operator variability in the ultrasonographic measurements of melanoma depth.Conclusions-We propose a ultrasonographic-histopathological protocol which may help clinicians to reduce the diagnostic delay, improve prognosis and survival rates, perform a surgical excision with negative margins, and reduce the variability in the assessment of Breslow thickness.