Reply to: "Estrogen could also play a key role in the development of pediatric melanoma"

To the Editor: We thank Dr Magnaterra et al1Magnaterra E. Zuccaro B. Magliulio M. et al.Estrogen could play a key role in the development of pediatric melanoma.J Am Acad Dermatol. 2023; (In press)Abstract Full Text Full Text PDF Scopus (0) Google Scholar for their interest in our recent article.2El Sharouni M.A. Rawson R.V. Potter A.J. et al.Melanomas in children and adolescents: clinicopathologic features and survival outcomes.J Am Acad Dermatol. 2022; 88: 609-616Abstract Full Text Full Text PDF Scopus (2) Google Scholar They state that they found unconvincing our suggestion that sex-specific differences in clinical and pathological findings could be relevant to the development of melanoma in pediatric and adolescent individuals. Curiously, they then go on to theorize that the slight female predominance that we observed (54.8% vs 45.2%) could be related to hormonal stimulation by estrogens. The hormonal disparities between males and females in fact represented one aspect of the sex-specific differences that we were alluding to as a possible explanation of that slight female predominance. However, it should be noted that although Australian national melanoma incidence data for the prepubertal age group (≤11 years of age, n = 68) also indicated a predominance of females (60.3%), data from the US National Cancer Database for melanoma patients <10 years of age (n = 164) indicated a predominance of males (56.7%). In the multivariable analyses that we conducted in our study, neither age (per 5 years) nor sex were associated with overall survival or recurrence-free survival. We agree with Magnaterra et al1Magnaterra E. Zuccaro B. Magliulio M. et al.Estrogen could play a key role in the development of pediatric melanoma.J Am Acad Dermatol. 2023; (In press)Abstract Full Text Full Text PDF Scopus (0) Google Scholar that little is known about the pathogenesis of melanoma in children, and that further research in this area is required. Elucidating the possible role of hormones in melanoma development is clearly important, but many other factors may be involved. It is well-documented that melanomas in children are rare, and that a rapid increase in melanoma incidence occurs at around the time of puberty, as observed in both sexes in our study2El Sharouni M.A. Rawson R.V. Potter A.J. et al.Melanomas in children and adolescents: clinicopathologic features and survival outcomes.J Am Acad Dermatol. 2022; 88: 609-616Abstract Full Text Full Text PDF Scopus (2) Google Scholar and also in Australian national data.3Friedman E.B. Scolyer R.A. Thompson J.F. Management of pigmented skin lesions in childhood and adolescence.Aust J Gen Pract. 2019; 48: 539-544Crossref Scopus (2) Google Scholar Less well documented is the melanoma incidence ratio between females and males in children, adolescents and in later life. As we highlighted in our article and as reported by Olsen et al,4Olsen C.M. Thompson J.F. Pandeya N. Whiteman D.C. Evaluation of sex-specific incidence of melanoma.JAMA Dermatol. 2020; 156: 553-560Crossref PubMed Scopus (46) Google Scholar there is a switch from female predominance in younger individuals developing melanoma to male predominance in older individuals in all countries, but this switch occurs at different ages in various parts of the world.4Olsen C.M. Thompson J.F. Pandeya N. Whiteman D.C. Evaluation of sex-specific incidence of melanoma.JAMA Dermatol. 2020; 156: 553-560Crossref PubMed Scopus (46) Google Scholar In Australia, for example, it occurs at 45-49 years of age, with more males than females developing melanoma thereafter, whereas in Denmark the switch does not occur until 65-69 years of age, ie, 20 years later (Fig 1). The age of the ratio switch does not appear to correlate with age of menopause, which the hypothesis of Magnaterra et al would anticipate. We also highlighted in our article the difference in melanoma incidence at various anatomic sites as another example of sex-specific differences, with higher rates of lower limb melanoma in early life in females and higher rates of head or neck melanoma in later life in males. The reason for these differences is unknown, and it seems likely that there is a complex interplay between inherited genetic predisposition and subsequent hormonal influences and environmental factors in the development of cutaneous melanomas at particular anatomic sites and at differing ages in both sexes. RAS has received fees for professional services from MetaOptima Technology Inc., F. Hoffmann-La Roche Ltd, Evaxion, Provectus Biopharmaceuticals Australia, Qbiotics, Novartis, Merck Sharp & Dohme, GlaxoSmithKline Australia, Bristol-Myers Squibb, Novartis, Myriad, NeraCare and AMGEN Inc. JFT has received honoraria for advisory board participation from BMS Australia, MSD Australia, GSK and Provectus Inc, and travel and conference support from GSK, Provectus Inc and Novartis. The other authors have no disclosures. Estrogen could also play a key role in the development of pediatric melanomaJournal of the American Academy of DermatologyPreviewTo the Editor: We read with interest “Melanomas in children and adolescents: clinicopathologic features and survival outcomes” by El Sharouni et al.1 The authors evaluated the clinicopathologic features, survival outcomes, and prognostic features of 514 pediatric melanomas (PMs) by pooling the data sets of the Melanoma Institute Australia and the Dutch Pathology Registry. Full-Text PDF