A meta-analysis of nevus-associated melanoma: Prevalence and practical implications

Pampena, Riccardo; Kyrgidis, Athanassios; Lallas, Aimilios; Moscarella, Elvira; Argenziano, Giuseppe; Longo, Caterina

doi:10.1016/j.jaad.2017.06.149

Cited by 151 publications

(152 citation statements)

References 49 publications

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“…In a gene sequencing study of melanocytic lesions, 77% of DN and melanoma in situ contained TPMs, which contribute to genomic instability and allow for additional time for cellular replication and associated mutations and the development of functional TMMs to bypass replicative senescence and achieve cellular immortalization . However, an estimated equal percentage of 20‐50% of melanomas arise adjacent to CMN or DN, arguing against an increased risk of MM development from DN. Thus, there is still debate about the progressive nature and oncogenic potential of DN, particularly in comparison with CMN …”

Section: Introductionmentioning

confidence: 99%

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Yan

Garcet

Gulati

et al. 2018

Experimental Dermatology

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Dysplastic nevi (DN) are benign lesions with atypical features intermediate between that of common melanocytic nevi (CMN) and malignant melanoma (MM). Debate remains over whether DN represent progressive lesions from CMN. Through gene expression profiling and analysis of molecular gene signatures, our study revealed progressive increases in immune activation and regulation, along with pathways implicated in melanomagenesis, from CMN to DN to MM. Using criteria of 1.5 fold change and false discovery rate ≤ 0.05, we found differential expression of 7,186 probes (6,370 unique genes) with the largest difference detected between DN and MM from the standpoint of genomic melanoma progression. Despite progressive increases in the T-helper type 1 (Th1) inducing gene (IL-12), RT-PCR indicated impaired Th1 or cytotoxic T-cell response (decreased IFN-γ) in MM. Concordantly, our results indicated progressive increases in molecular markers associated with regulatory T-cells, exhausted T-cells, and tolerogenic dendritic cells, including detection of increased expression of suppressor of cytokine signaling 3 (SOCS3) in dendritic cells associated with MM. All together, our findings suggest that the increased immunosuppressive microenvironment of melanoma may contribute to unhampered proliferation of neoplastic cells. In addition, the detection of increased markers associated with tolerogenic dendritic cells in MM suggest that targeting these suppressive immune cell types may represent an alternative avenue for future immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Yan

Garcet

Gulati

et al. 2018

Experimental Dermatology

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“…Exclusion criterion 2: >20% of subjects with atypical nevi considered to have also a suspected melanoma. Probably, in these countries, atypical nevi were erroneously considered as suspected melanomas and therefore excised, although nevi and atypical nevi only rarely transform into melanomas …”

Section: Methodsmentioning

confidence: 99%

Association of sunbed use with skin cancer risk factors in Europe: an investigation within the Euromelanoma skin cancer prevention campaign

Suppa

Gandini

Njimi

et al. 2019

Acad Dermatol Venereol

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Introduction Sunbed use has been significantly associated with increased risk of melanoma and non‐melanoma skin cancer (NMSC), but its relationship with melanoma's risk factors such as high nevus count, atypical nevi and lentigines is poorly studied. Euromelanoma is a skin cancer prevention campaign conducted all over Europe. It offers a once‐a‐year screening during which participants’ data, including sunbed use and phenotype, are collected via questionnaires. Objectives To investigate the association of sunbed use with nevus count, atypical nevi, lentigines and suspicion of skin cancer. Methods To ensure reliability of the data, we defined inclusion and exclusion criteria for countries’ eligibility for the risk analysis. Multivariate logistic regression models (including age, gender, education, skin type, family history of melanoma, personal history of skin cancer, any sun exposure and any sunscreen use) were used to calculate summary odds ratios (SORs) of each clinical endpoint for ever sunbed use. Results Overall, 227 888 individuals from 30 countries completed the Euromelanoma questionnaire. After the data quality check, 16 countries were eligible for the multivariate analysis, for a total of 145 980 participants (64.8% females; median age 43 years; 62.3% highly educated; 28.5% skin type I–II; 11.0% ever sunbed use). Ever sunbed use was independently associated with nevus count >50 [SOR = 1.05 (1.01–1.10)], atypical nevi [SOR = 1.04 (1.00–1.09)], lentigines [SOR = 1.16 (1.04–1.29)] and suspicion of melanoma [SOR = 1.13 (1.00–1.27)]. Conversely, no significant association was found between ever sunbed use and suspicion of NMSC [SOR = 1.00 (0.91–1.10)]. Conclusions Indoor tanning is significantly associated with well‐recognized risk factors for melanoma (including high nevus count, presence of atypical nevi and lentigines) as well as suspicion of melanoma within the Euromelanoma screenees. In order to reduce the prevalence of melanoma risk factors, avoidance/discontinuation of sunbed use should always be encouraged, especially but not exclusively for individuals with high‐risk phenotypes.

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“…The late Ackerman insisted that most MM did not develop from preceding melanocytic nevus of any kind but arose de novo by transformation of epidermal melanocytes . A recent meta‐analysis revealed that the majority of MM did not accompany any nevoid lesions, suggesting the de novo genesis of MM in most cases …”

Section: Introductionmentioning

confidence: 99%

Histogenesis of cutaneous malignant melanoma: The vast majority do not develop from melanocytic nevus but arise de novo as melanoma in situ

Saida

2019

The Journal of Dermatology

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It has been considered that most cutaneous malignant melanomas arise from pre‐existing melanocytic nevus. Many clinical and histopathological studies seem to support this concept. Dysplastic nevus originally proposed by Clark's group is a key entity of the intermediate lesion between benign nevus and melanoma. The latest edition of the WHO Classification of Skin Tumours (2018) has excluded Clark nevus (dysplastic nevus of mild atypia) from dysplastic nevus, the latter being now classified into the low‐ and high‐grade by the degrees of nuclear atypia. The World Health Organization classification regards dysplastic nevus of both grades as the intermediate lesion between common acquired nevus and the radial growth‐phase melanoma. An extensive genetic study recently performed by Bastian's group indicated the existence of intermediate lesions between nevus and melanoma. In spite of these findings, some investigators doubt the concept of the intermediate lesions including dysplastic nevus and insist that the majority of melanomas arise de novo as melanoma in situ, not in association with a preceding nevus. The concept of de novo genesis of melanoma may be supported by a recent meta‐analysis study revealing that 71% of melanomas likely arose de novo and 29% from pre‐existing nevus. In this review article, from the viewpoint of de novo genesis of melanoma, the author critically discusses the relevant findings of melanoma genesis and proposes a new framework to interpret the morphological and genetic data alternatively. Clarification of the oncogenic process of melanoma has great impact not only on clinical dermatology but also on basic oncology.

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A meta-analysis of nevus-associated melanoma: Prevalence and practical implications

Cited by 151 publications

References 49 publications

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Novel immune signatures associated with dysplastic naevi and primary cutaneous melanoma in human skin

Association of sunbed use with skin cancer risk factors in Europe: an investigation within the Euromelanoma skin cancer prevention campaign

Histogenesis of cutaneous malignant melanoma: The vast majority do not develop from melanocytic nevus but arise de novo as melanoma in situ

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