Clinics in Dermatology
Volume 27, Issue 1 , Pages 103-115 , January 2009

The “dysplastic” nevus

  • Robert J. Friedman, MD

      Affiliations

    • Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA
    • Corresponding Author InformationCorresponding author. 124 East 72nd Street, New York, NY 10021, USA.
  • ,
  • Michele J. Farber, BS

      Affiliations

    • Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
  • ,
  • Melanie A. Warycha, MD

      Affiliations

    • Department of Dermatology, New York University School of Medicine, New York, NY 10016, USA
  • ,
  • Nicole Papathasis, MD

      Affiliations

    • New York Medical College, Valhalla, NY 10595, USA
  • ,
  • Michael K. Miller, MD

      Affiliations

    • Dermpath Diagnostics, Port Chester, NY 10573, USA
  • ,
  • Edward R. Heilman, MD

      Affiliations

    • Departments of Dermatology and Pathology, Health Sciences Center, State University of New York at Brooklyn, Brooklyn, NY 11203, USA

References 

  1. Clark WH, Ackerman AB. An exchange of views regarding the dysplastic nevus controversy. Semin Dermatol. 1989;8:229–250
  2. Clark WH, Reimer RR, Greene M, et al. Origin of familial malignant melanomas from hereditary melanocytic lesions. ‘The B-K mole syndrome.’. Arch Dermatol. 1978;114:732–738
  3. Lynch HT, Frichot BC, Lynch JH. Familial atypical multiple mole melanoma syndrome. J Med Genet. 1978;15:352–355
  4. Elder DE, Goldman LI, Goldman SC, et al. Dysplastic nevus syndrome: phenotypic association of sporadic cutaneous melanoma. Cancer. 1980;46:1787–1794
  5. Consensus Statement . Diagnosis and treatment of early melanoma. In: NIH Consensus Development Conference, Jan 27-29. 1992;
  6. Tripp JM, Kopf AW, Marghoob AA, et al. Management of dysplastic nevi: survey of fellows of the American Academy of Dermatology. J Am Acad Dermatol. 2002;46:674–682
  7. Piepkorn M, Meyer LJ, Goldgar D, et al. The dysplastic melanocytic nevus: prevalent lesion that correlates poorly with clinical phenotype. J Am Acad Dermatol. 1989;20:407–415
  8. Crutcher WA, Sagebiel RW. Prevalence of dysplastic naevi in a community practice. Lancet. 1984;1:729
  9. Lee G, Massa MC, Welykyj S, et al. Yield from total skin examination and effectiveness of skin cancer awareness program. Findings in 874 new dermatology patients. Cancer. 1991;67:202–205
  10. Nordlund JJ, Kirkwood J, Forget BM, et al. Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects. Cancer Res. 1985;45:1855–1861
  11. Bataille V, Grulich A, Sasieni P, et al. The association between naevi and melanoma in populations with different levels of sun exposure: joint case-control study of melanoma in the UK and Australia. Br J Cancer. 1998;77:505–510
  12. Grob JJ, Gouvernet J, Aymar D. Count of benign melanocytic nevi as a major indicator of risk for nonfamilial nodular and superficial spreading melanoma. Cancer. 1990;66:387–395
  13. Holly EA, Kelly JW, Shpall SN, et al. Number of melanocytic nevi as a major risk factor for malignant melanoma. J Am Acad Dermatol. 1987;17:459–468
  14. Ng PC, Barzilai DA, Ismail SA, et al. Evaluating invasive cutaneous melanoma: is the initial biopsy representative of the final depth?. J Am Acad Dermatol. 2003;48:420–424
  15. Tucker MA, Halpern A, Holly EA, et al. Clinically recognized dysplastic nevi: a central risk factor for cutaneous melanoma. JAMA. 1997;277:1439–1444
  16. Roush GC, Nordund JJ, Forget B, et al. Independence of dysplastic nevi from total nevi in patients with melanoma and comparison subjects. Cancer Res. 1985;45:1855–1861
  17. Garbe C, Kruger S, Stadler R, et al. Markers and relative risk in a German population for developing malignant melanomas. Int J Dermatol. 1989;38:517–523
  18. Garbe C, Buttner P, Weiss J, et al. Associated factors in the prevalence of more than 50 common melanocytic nevi, atypical melanocytic nevi, and actinic lentigines: multicenter case-control study of the central melanoma registry of the German Dermatological Society. J Invest Dermatol. 1994;102:700–705
  19. Swerdlow AJ, English J, MacKie RM, et al. Benign melanocytic naevi as a risk factor for malignant melanoma. Br Med J (Clin Res Ed). 1986;292:1555–1559
  20. MacKie RM, Aitchison TC, Freudenberger T. Risk factors for melanoma. Lancet. 1989;2:928
  21. Augustsson A, Stierner U, Rosdahl I, et al. Common and dysplastic naevi as risk factors for cutaneous malignant melanoma in a Swedish population. Acta Dermatol Venereol. 1991;71:518–524
  22. Halpern AC, Guerry D, Elder DE, et al. Dysplastic nevi as risk markers of sporadic (nonfamilial) melanoma: case-control study. Arch Dermatol. 1991;127:995–999
  23. Halpern AC, Guerry D, Elder DE, et al. A cohort study of melanoma in patients with dysplastic nevi. J Invest Dermatol. 1993;100:346S–349S
  24. Tucker MA, Fraser MC, Goldstein AM, et al. Risk of melanoma and other cancers in melanoma-prone families. J Invest Dermatol. 1993;100:350S–355S
  25. Kraemer KH, Greene MH. Dysplastic nevus syndrome. Familial and sporadic precursors of cutaneous melanoma. Dermatol Clin. 1985;3:225–237
  26. Marghoob AA, Kopf AW, Rigel DS, et al. Risk of cutaneous malignant melanoma in patients with ‘classic’ atypical-mole syndrome. A case-control study. Arch Dermatol. 1994;130:993–998
  27. Shors AR, White KE, Argenyi Z, et al. Dysplastic naevi with moderate to severe histological dysplasia: risk factor for melanoma. Br J Dermatol. 2006;155:988–993
  28. Greene MH, Clark WH, Tucker MA, et al. Acquired precursors of cutaneous malignant melanoma:the familial dysplastic nevus syndrome. N Engl J Med. 1985;312:91–97
  29. Skender-Kalnenas TM, English DR, Heenan PJ. Benign melanocytic lesions: risk markers or precursors of cutaneous melanoma?. J Am Acad Dermatol. 1995;33:1000–1007
  30. Duray PH, Ernestoff MS. Dysplastic nevus in histologic contiguity with acquired nonfamilial melanoma. Clinicopathologic experience in a 100-bed hospital. Arch Dermatol. 1987;123:80–84
  31. Rhodes AR, Harrist TJ, Day CL, et al. Dysplastic melanocytic nevi in histologic association with 234 primary cutaneous melanomas. J Am Acad Dermatol. 1983;9:563–574
  32. Rivers JK, Kopf AW, Vinokur AF, et al. Clinical characteristics of malignant melanomas developing in persons with dysplastic nevi. Cancer. 1990;65:1232–1236
  33. Salopek TG, Friedman RJ. Dysplastic nevi. In:  Rigel DS,  Friedman RJ,  Dzubow LM, et al. editor. Cancer of the skin. Philadelphia: Saunders; 2005;p. 203–219
  34. Salopek TG, Kopf AW, Stefanato CM, et al. Differentiation of atypical moles (dysplastic nevi) from early melanomas by dermoscopy. Dermatol Clin. 2001;19:337–345
  35. Kelly JW, Yeatman JM, Regalia C, et al. A high incidence of melanoma found in patients with multiple dysplastic naevi by photographic surveillance. Med J Aust. 1997;167:191–194
  36. Naeyert JM, Brochez L. Dysplastic nevi. N Engl J Med. 2003;349:2233–2240
  37. de Wit PEJ, van't Hof-Grootenboer B, Ruiter DJ, et al. Validity of the histopathological criteria used for diagnosing dysplastic naevi: an interobserver study by the pathology subgroup of the EORTC malignant melanoma cooperative group. Eur J Can. 1993;29:831–839
  38. Weinstock MA, Barnhill RL, Rhodes AR, et al. Reliability of the histopathologic diagnosis of melanocytic dysplasia. The dysplastic nevus panel. Arch Dermatol. 1997;133:953–958
  39. Shea C, Vollmer R, Prieto V. Correlating architectural disorder and cytologic atypia in Clark (dysplastic) melanocytic nevi. Hum Pathol. 1999;30:500–505
  40. Pozo L, Naase M, Cerio R, et al. Critical analysis of histologic criteria for grading atypical (dysplastic) melanocytic nevi. Am J Clin Pathol. 2001;115:194–204
  41. Hussussian CJ, Struewing JP, Goldstein AM, et al. Germline p16 mutations in familial melanoma. Nat Genet. 1994;8:15–21
  42. Zuo L, Weger J, Yang Q, et al. Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma. Nat Genet. 1996;12:97–99
  43. Begg CB, Orlow I, Hummer AJ, et al. Lifetime risk of melanoma in cdkn2a mutation carriers in a population-based sample. J Natl Cancer Inst. 2005;97:1507–1515
  44. Thompson J, Scolyer R, Kefford R. Cutaneous melanoma. Lancet. 2005;365:687–701
  45. Goldstein AM, Struewing JP, Chidambaram A, et al. Genotype-phenotype relationships in U.S. melanoma-prone families with CDKN2A and CDK4 mutations. J Natl Cancer Inst. 2000;92:1006–1010
  46. Soufir N, Avril MF, Chompret A, et al. Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France: the French familial melanoma study group [published erratum appears in Hum Mol Genet 1998;7(5):941]. Hum Mol Genet. 1998;7:209–216
  47. Bishop DT, Demenais F, Goldstein AM, et al. Geographical variation in the penetrance of CDKN2A mutations for melanoma. J Natl Cancer Inst. 2002;94:894–903
  48. Goldstein AM, Martinez M, Tucker MA, et al. Gene-covariate interaction between dysplastic nevi and the CDKN2A gene in American melanoma-prone families. Cancer Epidemiol Biomarkers Prev. 2000;9:889–894
  49. Chaudru V, Chompret A, Bressac-de Paillerets B, et al. Influence of genes, nevi, and sun sensitivity on melanoma risk in a family sample unselected by family history and in melanoma-prone families. J Natl Cancer Inst. 2004;96:785–795
  50. Bishop JAN, Wachsmuch RC, Harland M, et al. Genotype/phenotype and penetrance studies in melanoma families with germline CDKN2A mutations. J Invest Dermatol. 2000;114:28–33
  51. Sini MC, Manca A, Cossu M, et al. Molecular alterations at chromosome 9p21 in melanocytic naevi and melanoma. Br J Dermatol. 2008;158:243–250
  52. Celebi JT, Ward KM, Wanner M, et al. Evaluation of germline CDKN2A, ARF, CDK4, PTEN, and BRAF alterations in atypical mole syndrome. Clin Exp Dermatol. 2005;30:68–70
  53. Lee JY, Dong SM, Shin MS, et al. Genetic alterations of p16INK4a and p53 genes in sporadic dysplastic nevus. Biochem Biophys Res Commun. 1997;237:667–672
  54. Perera MIR, Um K, Greene MH, et al. Hereditary dysplastic nevus syndrome: lymphoid cell ultraviolet hypermutability in association with increased melanoma susceptibility. Cancer Res. 1986;46:1005–1009
  55. Abrahams PH, Houweling A, Cornelissen-Steijger PDM, et al. Impaired DNA repair capacity in skin fibroblasts from various hereditary cancer-prone syndromes. Mut Res. 1998;407:189–201
  56. Noz KC, Bauwens M, van Buul PPW, et al. Comet assay demonstrates a higher ultraviolet B sensitivity to DNA damage in dysplastic nevus cells than in common melanocytic nevus cells and foreskin melanocytes. J Invest Dermatol. 1996;106:1198–1202
  57. Hussein MR, Sun M, Tuthill RJ, et al. Comprehensive analysis of 112 melanocytic skin lesions demonstrates microsatellite instability in melanomas and dysplastic nevi, but not in benign nevi. J Cut Pathol. 2001;28:343–350
  58. Pollock PM, Harper UL, Hansen KS, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003;33:19–20
  59. Patton EE, Widlund HR, Kutok JL, et al. BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr Biol. 2005;15:249–254
  60. Wellbrock C, Ogilvie L, Hedley D, et al. V599EB-RAF is an oncogene in melanocytes. Cancer Res. 2004;64:2338–2342
  61. Bennett DC, Cooper PJ, Hart IR. A line of non-tumorigenic mouse melanocytes, syngeneic with the B16 melanoma and requiring a tumour promoter for growth. Int J Cancer. 1987;39:414–418
  62. Loewe R, Kittler H, Fischer G, et al. BRAF kinase gene V599E mutation in growing melanocytic lesions. J Invest Dermatol. 2004;123:733–736
  63. Michaloglou C, Vredeveld LCW, Soengas MS, et al. tlBRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature. 2005;436:720–724
  64. Clark WH, Elder DE, Guerry D, et al. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol. 1984;15:1147–1165
  65. Bevona C, Goggins W, Quinn T, et al. Cutaneous melanomas associated with nevi. Arch Dermatol. 2003;139:1620–1624
  66. Whiteman DC, Watt P, Purdie DM, et al. Melanocytic nevi, solar keratoses, and divergent pathways to cutaneous melanoma. J Natl Cancer Inst. 2003;95:806–812
  67. Curtin JA, Fridlyand J, Kageshita T, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med. 2005;353:2135–2147
  68. Weinstock MA, Brodsky GL. Bias in the assessment of family history of melanoma and its association with dysplastic nevi in a case-control study. J Clin Epidemiol. 1998;51:1299–1303
  69. Salopek TG. The dilemma of the dysplastic nevus. Dermatol Clin. 2002;617–628
  70. Schmid-Wendtner MH, Berking C, Baumert J, et al. Cutaneous melanoma in childhood and adolescence: n analysis of 36 patients. J Am Acad Dermatol. 2002;46:874–879
  71. Haley JC, Hood AF, Chuang TY, et al. The frequency of histologically dysplastic nevi in 199 pediatric patients. Pediatr Dermatol. 2000;17:266–269
  72. Halpern AC, Guerry D, Elder DE. Natural history of dysplastic nevi. J Am Acad Dermatol. 1993;29:51–57
  73. Hansson J, Bergenmar M, Hofer PA, et al. Monitoring kindreds with hereditary predisposition for cutaneous melanoma and dysplastic nevus syndrome: results of a Swedish preventative program. J Clin Oncol. 2007;25:2819–2824
  74. Rodriguez-Sains RS. Ocular findings in patients with dysplastic nevus syndrome. Ophthalmology. 1986;93:661–665
  75. van Hees CL, de Boer A, Jager MJ, et al. Are atypical nevi a risk factor for uveal melanoma? A case-control study. J Invest Dermatol. 1994;103:202–205
  76. Vajdic CM, Kricker A, Giblin M, et al. Eye color and cutaneous nevi predict risk of ocular melanoma in Australia. Int J Cancer. 2001;92:906–912
  77. Soyer HP, Smolle J, Leitinger G, et al. Diagnostic reliability of dermoscopic criteria for detecting malignant melanoma. Dermatology. 1995;190:25–30
  78. Kittler H, Pehamberger H, Wolff K. Diagnostic accuracy of dermoscopy. Lancet Oncol. 2002;3:159–165
  79. Bafounta ML, Beauchet A, Aegerter P, Saiag P. Is dermoscopy (epiluminescence microscopy) useful for the diagnosis of melanoma?. Arch Dermatol. 2001;137:1343–1350
  80. Binder M, Schwartz M, Winkler A, et al. Epiluminescence microscopy: useful tool for the diagnosis of pigmented skin lesions for formally trained dermatologists. Arch Dermatol. 1995;131:286–291
  81. Argenziano G, Soyer HP, Chimenti S, et al. Dermoscopy of pigmented skin lesions:results of a consensus meeting via the Internet. J Am Acad Dermatol. 2003;48:679–693
  82. Soyer HP, Argenziano G, Zalaudek I, et al. Three-point checklist of dermoscopy. Dermatology. 2004;208:27–31
  83. Hofmann-Wellenhoff R, Blum A, Wolf IH, et al. Dermoscopic classification of Clark's nevi (atypical melanocytic nevi). Clin Dermatol. 2002;20:255–258
  84. Lucas CR, Sanders LL, Murray JC, et al. Early melanoma detection: nonuniform dermoscopic features and growth. J Am Acad Dermatol. 2003;48:663–671
  85. Banky JP, Kelly JW, English DR, et al. Incidence of new and changed nevi and melanomas detected using baseline images and dermoscopy in patients with high risk for melanoma. Arch Dermatol. 2005;141:998–1006
  86. Friedman RJ, Gutkowicz-Krusin D, Farber MJ, et al. The diagnostic performance of expert dermoscopists vs a computer-vision system on small-diameter melanomas. Arch Dermatol. 2008;144:476–482
  87. Kefford RF, Newton Bishop JA, Bergman W, et al. Counseling and DNA testing for individuals perceived to be genetically predisposed to melanoma: consensus statement of the Melanoma Genetics Consortium. J Clin Oncol. 1999;17:3245–3251
  88. Stratigos AJ, Dover JS, Arndt KA. Laser treatment of pigmented lesions–2000: how far have we gone?. Arch Dermatol. 2000;136:915–921
  89. Kelly JW, Rivers JK, MacLennan R, et al. Sunlight: major factor associated with the development of melanocytic nevi in Australian schoolchildren. J Am Acad Dermatol. 1994;30:40–48
  90. Gallagher RP, Rivers JK, Lee TK, et al. Broad-spectrum sunscreen use and the development of new nevi in white children: randomized controlled trial. JAMA. 2000;283:2955–2960

PII: S0738-081X(08)00185-5

doi: 10.1016/j.clindermatol.2008.09.008

Clinics in Dermatology
Volume 27, Issue 1 , Pages 103-115 , January 2009