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Several studies have suggested that naevus-associated melanomas differ from de novo melanomas, being thinner and with less ulceration; however, the prognostic implication is unclear. The objective of this study was to describe clinicopathological, genetic and survival characteristics of de novo and naevus-associated melanomas in a cohort of primary invasive cutaneous melanomas over a 20-year period. Of the 2,227 patients included in the study, 509 (22.86%) had naevus-associated melanomas. Compared with patients with de novo melanoma, they were younger, with a fairer phototype and a higher naevus count, tumours were predominantly the superficial spreading subtype, American Joint Committee on Cancer stage I, located on the trunk, and there were fewer signs of invasiveness (thinner Breslow index, less ulceration, lower mitotic index and less satellitosis). Germline mutation-al status did not show any significant association. As determined through univariate analysis, overall surviv-al was significantly better in patients with naevus- associated melanoma (hazard ratio 0.64; 95% confidence interval 0.51-0.80, p < 0.001), but multivariate analysis did not support this prognostic indication (hazard ratio 0.94; 95% confidence interval 0.75-1.18, p < 0.606). Despite this, we conclude that naevus- associated and de novo melanomas should be considered as different subtypes of melanoma.

Numerous dermoscopic structures for the early detection of melanoma have been described. The aim of this study was to illustrate the characteristics of dermoscopic structures that are similar to blotches, but smaller (termed microblotches), and to evaluate their association with other well-known dermoscopic structures. A cross-sectional study design, including 165 dermoscopic images of melanoma was used to define microblotches, and 241 consecutive images of naevi from the HAM10000 database, were studied to evaluate the prevalence of this criterion in both groups. Microblotches were defined as sharply demarcated structures ≤1 mm, with geographical borders visible only with dermoscopy. Microblotches were present in 38.7% of the melanomas and 6.7% of the naevi. Moreover, microblotches were associated with an odds ratio (OR) of malignancy of 5.79, and were more frequent in invasive melanoma than in the in-situ subtype (OR 2.92). Histologically, they correspond to hyperpigmented parakeratosis or epidermal consumption. In conclusion, microblotches are related to melanomas. This finding could help dermatologists to differentiate between naevi and melanomas.

Background: Blue nevi are benign dermal melanocytic proliferations that are often easy to recognize clinically. Rarely, these lesions can display atypical features, suggesting the presence of a malignant blue nevus or mimicking cutaneous metastases of melanoma. Objective: To describe the clinical evolution of blue nevi over time and to assess the need for monitoring these lesions. Methods: We conducted a retrospective cohort study of 103 patients who were followed between December 1998 and November 2019. An artificial intelligence algorithm was used to identify blue nevi from the databases of two digital epiluminescence devices. Changes in the area of each lesion were calculated with a segmentation neural network. Results: We included 123 blue nevi from 103 patients. Most of the lesions segmented, 99 (91.7%), were considered stable. Of the 9 (8.3%) growing blue nevi identified, 2 (1.85%) showed significant growth. The studied growing blue nevi turned out to be cellular blue nevi, presented with a low tumour mutation burden and GNAQ c.626A>T alteration was identified in both lesions. Limitations: Some clinical variants of blue nevi might not be included. Conclusions: Most blue nevi remain stable during their evolution. Rarely, they can show progressive growth, although histopathological or molecular signs of malignancy have not been identified. [ABSTRACT FROM AUTHOR]

Summary: Background: Hypomorphic MC1R variants are the most prevalent genetic determinants of melanoma risk in the white population. However, the genetic background of patients with wildtype (WT) MC1R melanoma is poorly studied. Objectives: To analyse the role of candidate common genetic variants on the melanoma risk and naevus count in Spanish patients with WT MC1R melanoma. Methods: We examined 753 individuals with WT MC1R from Spain (497 patients and 256 controls). We used OpenArray reverse‐transcriptase polymerase chain reaction to genotype a panel of 221 common genetic variants involved in melanoma, naevogenesis, hormonal pathways and proinflammatory pathways. Genetic models were tested using multivariate logistic regression models. Nonparametric multifactor dimensionality reduction (MDR) was used to detect gene–gene interactions within each biological subgroup of variants. Results: We found that variant rs12913832 in the HERC2 gene, which is associated with blue eye colour, increased melanoma risk in individuals with WT MC1R [odds ratio (OR) 1·97, 95% confidence interval (CI) 1·48–2·63; adjusted P < 0·001; corrected P < 0·001]. We also observed a trend between the rs3798577 variant in the oestrogen receptor alpha gene (ESR1) and a lower naevus count, which was restricted to female patients with WT MC1R (OR 0·51, 95% CI 0·33–0·79; adjusted P = 0·002; corrected P = 0·11). This sex‐dependent association was statistically significant in a larger cohort of patients with melanoma regardless of their MC1R status (n = 1497; OR 0·71, 95% CI 0·57–0·88; adjusted P = 0·002), reinforcing the hypothesis of an association between hormonal pathways and susceptibility to melanocytic proliferation. Last, the MDR analysis revealed four genetic combinations associated with melanoma risk or naevus count in patients with WT MC1R. Conclusions: Our data suggest that epistatic interaction among common variants related to melanocyte biology or proinflammatory pathways might influence melanocytic proliferation in individuals with WT MC1R. What is already known about this topic?Genetic variants in the MC1R gene are the most prevalent melanoma genetic risk factor in the white population. Still, 20–40% of cases of melanoma occur in individuals with wildtype MC1R.Multiple genetic variants have a pleiotropic effect in melanoma and naevogenesis. Additional variants in unexplored pathways might also have a role in melanocytic proliferation in these patients.Epidemiological evidence suggests an association of melanocytic proliferation with hormonal pathways and proinflammatory pathways. What does this study add?Variant rs12913832 in the HERC2 gene, which is associated with blue eye colour, increases the melanoma risk in individuals with wildtype MC1R.Variant rs3798577 in the oestrogen receptor gene is associated with naevus count regardless of the MC1R status in female patients with melanoma.We report epistatic interactions among common genetic variants with a role in modulating the risk of melanoma or the number of naevi in individuals with wildtype MC1R. What is the translational message?We report a potential role of hormonal signalling pathways in melanocytic proliferation, providing a basis for better understanding of sex‐based differences observed at the epidemiological level.We show that gene–gene interactions among common genetic variants might be responsible for an increased risk for melanoma development in individuals with a low‐risk phenotype, such as darkly pigmented hair and skin. [ABSTRACT FROM AUTHOR]

Nevus count is highly determined by inherited variants and has been associated with the origin of melanoma. De novo melanomas (DNMMs) are more prevalent in patients with a low nevus count and have distinctive dermoscopic features than nevus‐associated melanomas. We evaluated the impact of nine single nucleotide polymorphisms (SNPs) of MTAP (rs10811629, rs2218220, rs7023329 and rs751173), PLA2G6 (rs132985 and rs2284063), IRF4 (rs12203592), and PAX3 (rs10180903 and rs7600206) genes associated with nevus count and melanoma susceptibility, and the MC1R variants on dermoscopic features of 371 melanomas from 310 patients. All MTAP variants associated with a low nevus count were associated with regression structures (peppering and mixed regression), blue‐whitish veil, shiny white structures, and pigment network. SNPs of PLA2G6 (rs132985), PAX3 (rs7600206), and IRF4 (rs12203592) genes were also associated with either shiny white structures or mixed regression (all corrected p‐values ≤.06). Melanomas from red hair color MC1R variants carriers showed lower total dermoscopy score (p‐value =.015) and less blotches than melanomas from non‐carriers (p‐value =.048). Our results provide evidence that germline variants protective for melanoma risk and/or associated with a low nevus count are associated with certain dermoscopic features, more characteristic of de novo and worse prognosis melanomas. [ABSTRACT FROM AUTHOR]

Introduction: Alopecia areata (AA) is a high-prevalence immuno-mediated hair loss disorder. Extra follicular affections, including nail and ocular abnormalities, are classically related to a worse prognosis of the disease, and previous studies have suggested that the presence of a persistent nuchal nevus flammeus (NNF) also indicates a greater severity and duration of the disease. The association between AA and persistent NNF was first described by Hatzis et al in 1988, who demonstrated that the relation was statistically evident and not due to a simple observer bias. Objectives: To determine and compare the presence/absence and size of the NNF in 80 individuals (40 patients diagnosed with AA and 40 controls). Results: We found a statistically significant association not only between AA and the presence of NNF, but also with its size. Moreover, we found that the size of the NNF was also associated with the severity of AA. Conclusion: The size of the NNF in AA patients might be a useful marker of widespread and chronic disease. [ABSTRACT FROM AUTHOR]