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Age distribution of biopsied junctional nevi—Unna's concept versus a dual concept of nevogenesis

2007; Elsevier BV; Volume: 57; Issue: 6 Linguagem: Inglês

10.1016/j.jaad.2007.08.028

1097-6787

Iris Zalaudek, Ashfaq A. Marghoob, Alon Scope, Rainer Hofmann‐Wellenhof, Gerardo Ferrara, Giuseppe Argenziano,

Cutaneous Melanoma Detection and Management

To the Editor: We read with interest the article by Westhafer et al1Westhafer J. Gildea J. Klepeiss S. Clarke L. Helm K. Age distribution of biopsied junctional nevi.J Am Acad Dermatol. 2007; 56: 825-827Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar in the May 2007 issue of the Journal, in which the authors present the results of a retrospective study investigating patient age and location of biopsied junctional nevi. On the basis of their findings, the authors conclude that junctional nevi are common in all ages with a similar distribution in the young and the elderly. In addition, they noted that junctional nevi were more common on skin that was not chronically sun exposed. These findings led the authors to question Unna's concept of nevogenesis, which suggests that nevi begin as junctional nevi in childhood, mature into compound nevi, and finally end up as dermal nevi in adulthood. We agree that Unna's unifying concept cannot adequately explain the authors' findings or the many new insights into nevogenesis that we have acquired over the past decade. Unfortunately, the authors do not sufficiently address some of these points. First, the authors question Unna's concept of nevogenesis but fail to provide a reasonable or alternative theory that could explain the results of their study. Second, the authors conclude that junctional nevi are common in all ages, but they do not address the observation that the peak incidence of junctional nevi in their series occurred during midlife, whereas the incidence in children and the elderly was found to be relatively low. Third, such study design carries a general risk of selection bias, which may not reflect reality. On the basis of dermoscopic studies on the age-related dermoscopic patterns of nonexcised acquired nevi, we know today that nevi developing before puberty exhibit mostly a dermoscopic globular and/or homogeneous pattern, whereas nevi seen at or after puberty tend to harbor a reticular pattern.2Zalaudek I. Hofmann-Wellenhof R. Soyer H.P. Ferrara G. Argenziano G. Naevogenesis: new thoughts based on dermoscopy.Br J Dermatol. 2006; 154: 793-794Crossref PubMed Scopus (36) Google Scholar These dermoscopic features correspond to specific underlying histopathologic correlates. The globular/homogeneous patterned nevi tend to be seen in small congenital melanocytic nevi, compound nevi, or dermal nevi. On the other hand, reticular pattern nevi tend to be seen in junctional nevi. These striking age-related differences in the dermoscopic pattern of acquired nevi in vivo along with their different epidemiologic, clinical, and histopathologic features led us recently to propose a dual concept of nevogenesis,2Zalaudek I. Hofmann-Wellenhof R. Soyer H.P. Ferrara G. Argenziano G. Naevogenesis: new thoughts based on dermoscopy.Br J Dermatol. 2006; 154: 793-794Crossref PubMed Scopus (36) Google Scholar which might explain some of the findings by Westhafer et al. This dual concept states that dermoscopically globular nevi (i.e., congenital melanocytic nevi, compound nevi, and dermal nevi) develop via an “endogenous” pathway involving mutations in c-kit, c-met, or N-ras, which may cause melanoblast migration arrest in the dermis.3Bauer J. Curtin J.A. Pinkel D. Bastian B.C. Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations.J Invest Dermatol. 2007; 127: 179-182Crossref PubMed Scopus (243) Google Scholar These nevi commonly persist throughout life and rarely regress. In contrast, reticular nevi (ie, junctional nevi) represent true “acquired” nevi, which develop in response to exogenous factors, such as intermittent ultraviolet exposure (ie, “exogenous” pathway). Previous studies have indeed shown a steady increase followed by a decrease in the number of nevi before and after midlife, respectively. Today, many researchers are of the opinion that intermittent rather than long-term sun exposure is the key factor in the development and disappearance of nevi. It is theorized that intermittent ultraviolet exposure may cause BRAF mutations in melanocytic stem cells at the dermoepidermal junction. This in turn may cause the mutated stem cell to proliferate and form a nevus; however, if the host's cell-cycle checkpoint regulators are functioning normally, the cells would eventually enter senescence.4Michaloglou C. Vredeveld L.C. Soengas M.S. Denoyell C. Kuliman T. Van der Horst C.M. et al.BRAFE600-associated senescence-like cell cycle arrest of human naevi.Nature. 2005; 7051: 720-724Crossref Scopus (1639) Google Scholar Furthermore, it has been observed by many researchers that these true “acquired” nevi often undergo spontaneous regression later in life. These observations explain not only the high prevalence of junctional nevi on skin sites that are not chronically sun exposed found in the study by Westhafer et al,1Westhafer J. Gildea J. Klepeiss S. Clarke L. Helm K. Age distribution of biopsied junctional nevi.J Am Acad Dermatol. 2007; 56: 825-827Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar but also explain the peak incidence of junctional nevi they observed during midlife. In sum, the results reported by Westhafer et al can be plausibly explained in the view of our dual concept of nevogenesis.2Zalaudek I. Hofmann-Wellenhof R. Soyer H.P. Ferrara G. Argenziano G. Naevogenesis: new thoughts based on dermoscopy.Br J Dermatol. 2006; 154: 793-794Crossref PubMed Scopus (36) Google Scholar Finally, we agree with the authors that our current concept of nevus classification requires revision and we have proposed therefore a new classification of nevi based on dermoscopy.5Argenziano G. Zalaudek I. Ferrara G. Hofmann-Wellenhof R. Soyer H.P. Proposal of a new classification system for melanocytic naevi.Br J Dermatol. 2007; 157: 217-227Crossref PubMed Scopus (80) Google Scholar