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Atypical/Dysplastic Nevi at a Glance
  • Prevalence among Caucasian young adults roughly 10%; varies by population.
  • Flat (totally or partially flat with central elevation), large (>5 mm) lesions with irregular shape, indistinct borders, and variable pigmentation.
  • Risk markers for melanoma.
  • Most frequent on sun-exposed areas, especially intermittently exposed, such as back.
  • Associated with large numbers of common acquired nevi.
  • Majority of lesions will involute and disappear over time.
  • Histologic features include presence of immature, disordered growth pattern with a lymphocytic host response and random cytologic atypia in melanocytes.

Common atypical/dysplastic nevi were first recognized as distinct melanocytic neoplasias during the clinical assessment of melanoma-prone families.1 The nomenclature associated with these lesions also includes B–K moles (recognizing the first two families described whose surnames began with B and K),1 familial atypical multiple mole and melanoma syndrome,2 atypical mole syndrome,3 Clark's nevus,4 atypical moles, and nevus with architectural disorder (with varying degrees of melanocytic atypia).5 The nomenclature has been contentious. The term dysplastic nevus (DN) is frequently used both for clinical and histologic diagnoses,6,7 and it is the term that will be used in this chapter. Although not covered in this chapter, it is also important to note that the terms dysplastic and atypical may also be occasionally used as a modifier for other melanocytic neoplasias (i.e., Spitz nevi) or hyperplasias to indicate a distinct histologic variant from a typical pattern or an increased concern for malignancy.

DN are frequently found in melanoma-prone families in North America, Europe, and Australia.816 One cross-sectional study in a New Zealand cohort (independent of melanoma) revealed DN in 9% of European descent adults.17 A joint case-control study of nevi and melanoma in Australia and the United Kingdom demonstrated that DN were three times more frequent in the Australian controls (6%) than in the British controls (2%).18 There are a few case reports of DN in Japanese, primarily in melanoma-prone families.19

DN occur in a familial pattern; limited segregation analyses suggest an autosomal dominant transmission of the trait.20 However germ-line susceptibility genes have not yet been identified for DN. Germ-line mutation testing of candidate genes for melanoma (e.g., PTEN, BRAF, and CDK4) did not reveal an association with DN.21 Germ-line polymorphisms in BRAF were also not related to nevi or freckles in another study.22 Within families having CDKN2A germ-line mutations, DN appear to be an independent risk factor for melanoma.11,23 Earlier, linkage analyses in twin studies found evidence of a gene for increased number of nevi in the region around CDKN2A24,25 and recent genome wide association studies suggest that is close to MTAP26,27. Areas of modest interest have also been linked to areas on chromosomes 1, 6, and X.25 Thus, it is likely that DN, like melanoma, is a complex, heterogeneous trait.


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