Background: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears de novo for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM more frequently develops in association with a dysplastic or common melanocytic nevus. Objectives: To conduct a systematic review and meta-analysis to investigate the proportion of dysplastic or common melanocytic nevus in NAM associated with acquired nevus. Methods: A systematic literature search is conducted using PubMed, Scopus, and the Cochrane Library. The PRISMA checklist is used. Studies reporting patients diagnosed with NAM arising in an acquired common or dysplastic melanocytic nevus are included. A meta-analysis of proportions is performed using the random-effects model. The magnitude of heterogeneity is assessed with the I² statistic. Results: A total of 22 studies with 2174 NAMs with an acquired nevus (dysplastic or common) are included. The proportion of dysplastic nevus in NAM varies considerably in the included studies, ranging from 0% to 100%. In the meta-analysis, the overall estimate of the proportion of having a dysplastic nevus in NAM is 51% (95% CI: 39–63%) with high heterogeneity at I²: 95.8% (p < 0.01). A sensitivity meta-analysis of 12 studies that included 30 or more acquired nevus-NAMs (2023 cases) shows that 65% of the NAMs developed in a dysplastic nevus (95% CI: 51–77%). In a meta-analysis of 4 studies reporting invasive-only acquired nevus-NAMs (764 cases), the proportion of dysplastic nevus is 56% (95% CI: 36–75%). Only 2 studies are found reporting in situ NAMs with an acquired nevus, and the pooled estimated proportion of dysplastic nevus is 71% (95% CI: 63–78%). Conclusions: The results of this meta-analysis suggest a higher proportion of dysplastic nevus in acquired nevus-NAM; however, there is considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive melanomas, thin tumors, and by histological subtype.

Citation: Befon A, Katoulis AC, Georgala S, Katsampas A, Chardalia V, Melpidou A, Tzanetakou V, Chasapi V, Polydorou D, Desinioti C, Plaka M, Rigopoulos D, Stratigos AJ. Serum total 25-hydroxyvitamin D levels in patients with cutaneous malignant melanoma: a case-control study in a low-risk Southern European population. Dermatol Pract Concept. 2020;10(1):e2020010. DOI: https://doi.org/10.5826/dpc.1001a10 Accepted: September 24, 2019; Published: December 31, 2019 Copyright: ©2019 Befon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: None. Competing interests: The authors have no conflicts of interest to disclose. Authorship: All authors have contributed significantly to this publication. Corresponding author: Dr. Angeliki Befon, First Department of Dermatology and Venereology, University of Athens, Andreas Syggros Hospital, 5 Dragoumi str, Athens 16121, Greece. Email: drbefon@yahoo.gr Background: Recent data have shown an inverse association between serum 25-hydroxyvitamin D concentration and incidence of several cancers, including cutaneous malignant melanoma (CMM). In addition, lower serum 25-hydroxyvitamin D levels have been associated with thicker or higher stage melanomas and worse survival in observational studies. Materials and Methods: Ninety-nine patients diagnosed with primary CMM and 97 matched healthy controls entered the study. Demographic characteristics, risk factors for CMM, and clinical and histological characteristics were recorded for patients with primary CMM. Total serum 25-hydroxyvitamin D levels of melanoma patients measured by fully automated chemiluminescent vitamin D total immunoassay (Elecsys vitamin D total, Roche) at the time of diagnosis were compared with those of healthy controls. In addition, we tested the association of serum total 25-hydroxyvitamin D levels at melanoma diagnosis with known risk and prognostic factors for CMM. Results: Of the melanoma patients, 49 (49.49%) had deficient serum total 25-hydroxyvitamin D levels (30 ng/mL). The median serum total 25-hydroxyvitamin D levels were significantly lower in melanoma patients (20.62 ng/mL) compared with healthy controls (24.71 ng/mL), but statistical significance was not reached (chi-square test, P = 0.051) No statistically significant association was found between serum total 25-hydroxyvitamin D levels and demographic characteristics; risk factors for CMM; prognostic factors, such as Breslow thickness and ulceration; as well as clinical characteristics, such as melanoma stage, clinical type, and location. Conclusions: Lower serum 25-hydroxyvitamin D levels were found in our Greek cohort of melanoma patients compared with healthy controls, without reaching, however, statistical significance; these levels were not statistically associated with established risk and prognostic factors for CMM. Keywords : malignant melanoma, vitamin D, Breslow thickness, ulceration, risk factors, prognosis This work is licensed under a Creative Commons Attribution 4.0 International License.

Background/Objectives: Cutaneous melanoma is predominantly sporadic, although a subset of patients presents clinical features suggestive of inherited susceptibility. We introduced the pragmatic concept of genetically enriched (GE) melanoma, defined by the presence of early-onset melanoma, familial melanoma, or multiple primary melanomas. Methods: Its clinicopathological characteristics and prognosis were compared with those of sporadic melanoma. Demographic, clinicopathological, and survival data were analyzed using descriptive statistics, survival analysis, and Cox regression models. Results: In this retrospective single-center study, 1,874 patients were classified as having GE (n = 796, 42.5%) or sporadic melanoma (n = 1,078, 57.5%). Patients with GE melanoma were significantly younger at diagnosis (median age, 37 years [IQR 32–43] vs 57 years [IQR 50–66], p < 0.001) and were more frequently females than those with sporadic melanoma (56.8% vs. 51.4%, p = 0.024). The GE cohort also showed a distinct clinicopathological profile, with a higher proportion of melanoma in situ (20.2% vs. 15.2%), lower proportions of acral lentiginous (3.5% vs. 1.1%) and lentigo maligna (5.2% vs. 1.4%) melanoma, and a lower prevalence of previous malignancies. After a median follow-up of 8 years, disease-free survival did not differ significantly between the two cohorts (log-rank p = 0.23). Within the GE cohort, older age and male sex were associated with a higher risk of recurrence. Conclusions: Overall, patients fulfilling clinical criteria suggestive of inherited melanoma susceptibility appear to represent a distinct clinicopathological subgroup without evidence of poorer prognosis. The concept of GE melanoma may offer a pragmatic framework for identifying patients who may benefit from genetic counseling and tailored surveillance strategies.