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Atypical Mole (Dysplastic Nevus)

  • Author: Manuel Valdebran, MD; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jan 12, 2015
 

Background

In 1820, Norris proposed an association between nevi and melanoma. He described a family in which 2 members developed melanoma, while other family members had "many moles on various parts of their bodies." However, the exact appearance of these lesions is unknown.

In 1974, Munro[1] described an association of lesions and a family history of melanoma. These nevi had the clinical and microscopic appearance of what are now called atypical moles (AMs). In 1978 and 1981, Clark et al[2, 3] described these lesions as dysplastic nevi when they were observed as a familial phenomenon.

Atypical moles and dysplastic nevi are acquired melanocytic lesions of the skin whose clinical and histologic definitions are controversial and still evolving. Numerous definitions and criteria have been proposed, including the use of the term atypical moles for clinically abnormal nevi and dysplastic nevi for histologically abnormal nevi. Unfortunately, when clinically abnormal nevi are evaluated histologically, some studies have shown a lack of concordance, with some clinically abnormal nevi having no dysplastic features and some normal-appearing nevi having some dysplastic features.[4, 5, 6]

The terms atypical moles and dysplastic nevi continue to be used interchangeably, regardless of clinical or histologic appearance. Modern molecular methods, including genetic markers, cytokines, proliferation indexes, and cyclins, are all undergoing study to help determine which atypical moles may progress to melanoma, although no single marker has been determined.[7, 8, 9, 10]

Atypical moles differ from common acquired melanocytic nevi in several respects, including diameter and lack of pigment uniformity. Confusion exists because some atypical moles cannot be clinically distinguished from melanoma. The clinical and histologic appearances of atypical moles occurring in a familial setting appear to overlap with sporadically occurring atypical moles.

The US National Institutes of Health Consensus Conference on the diagnosis and treatment of early melanoma defined a syndrome of familial atypical mole and melanoma (FAMM). The criteria for FAMM syndrome are as follows[11] :

  • The occurrence of malignant melanoma in 1 or more first- or second-degree relatives
  • The presence of numerous (often >50) melanocytic nevi, some of which are clinically atypical
  • Many of the associated nevi showing certain histologic features (see Histologic Findings)

See Mole or Melanoma? Test Yourself With These Suspicious Lesions, a Critical Images slideshow, to help identify various skin lesions.

For additional information on malignant melanoma, see Malignant Melanoma. Additionally, the Medscape Skin Cancer Resource Center and Melanoma Resource Center may be helpful.

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Pathophysiology

Atypical moles can be inherited or sporadic. Formal genetic analysis has suggested an autosomal dominant mode of inheritance but genetic studies have not shown consistent data.

Germline mutations in 3 genes, CDK2NA[12] and CDK4,[13] mapped to 9p21 and 12q14, and CMM1, mapped to 1p,[14] have been linked to a subset of hereditary melanomas and FAMM syndrome. In addition, somatic mutations in PTEN,BRAF,[15] and MCR1 (melanocortin-1 receptor)[16] have been associated with melanoma. Other genomic events such as loss of heterozygosity (LOH) for tumor suppressor genes are also responsible for the progression from atypical nevi to melanoma,[17] and the genes thought to be responsible for most familial and sporadic atypical moles are still unknown.

Ultraviolet (UV) light (UV-A and UV-B) has been proposed as both an initiator and a promoter in the transformation of melanocytes into atypical melanocytes or melanoma. The International Agency for Research on Cancer raised the classification of UV-emitting tanning devices from "probable carcinogenic to humans" to "carcinogenic to humans,"[18] and a meta-analysis concluded that use of UV tanning beds before age 30 years increases the risk of melanoma by 75%.[19] UV light exposure may be required for full expression of FAMM syndrome.

Genetics and UV radiation may also result in a variable number and anatomical distribution of melanocytic nevi. Some patients with the atypical mole syndrome have many large and highly atypical nevi, whereas other patients with this syndrome have many nevi but only a few are atypical.

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Epidemiology

Frequency

United States

The prevalence of atypical moles in white populations has been reported to be as high as 17%.[20] Atypical moles can be inherited or occur sporadically. Familial atypical moles may be inherited as an autosomal dominant trait. Sporadic lesions are those atypical moles that occur in patients without a family history of atypical moles.[21]

International

In Australia and New Zealand, the prevalence of atypical moles has been reported to be 5-10%.[22] In Germany, approximately 2% of 500 white males aged 16-25 years were reported to have atypical moles on biopsy analysis. Eighteen percent of a population of white adults studied in Sweden were determined to have atypical moles clinically, although only 8% demonstrated histologic features of atypical moles. The marked differences in prevalence between different populations may be due to true differences between these populations or they may be related to differing clinical and histologic definitions of this entity.

Mortality/Morbidity

Melanoma can develop from precursor nevi and atypical moles. While many melanomas arise de novo, superficial spreading melanoma may arise from atypical moles.[23] The exact risk of an individual nevus transforming into a melanoma is thought to be 1 in 200,000, and cutaneous melanomas are associated with precursor lesions at least 50% of the time in patients younger than 30 years.[24] Patients with numerous atypical moles are at a higher risk of developing melanoma than those individuals with only a few atypical moles. This risk is more pronounced with a family history of melanoma.[25, 26]

A personal or family history of melanoma is more predictive for the future development of a melanoma than is the number of atypical moles.

Among whites in the United States, the lifetime risk of developing a cutaneous melanoma is approximately 0.6%, or 1 in 150 individuals. In some studies of patients with FAMM, the overall lifetime risk of melanoma has been estimated to be 100%.[27]

The risk of melanoma is greater for those individuals who have 1 relative with melanoma than for those with no affected relative. The lifetime risk of melanoma may approach 100% in individuals with atypical moles who are from families prone to melanoma (ie, families having 2 or more first-degree relatives with melanoma).

Individuals who have nevi with clinical or histologic characteristics of atypical moles but no family history of atypical moles or melanoma might also be at an increased risk for the development of melanoma. Several prospective studies have demonstrated that patients with atypical moles without an obvious family history of melanoma have an increased risk for the occurrence of melanoma.[21, 28] However, the relative risks for melanoma are lower than in those individuals with a clear family history of melanoma. Thus, the presence of atypical moles (sporadic or familial) may identify patients at increased risk for melanoma, much like fair skin or UV exposure.

Race

Individuals at the highest risk of atypical moles are persons of northern European background (Celtic) with light-colored hair and freckles. Atypical moles are rare in black, Asian, or Middle Eastern populations.

Sex

No sexual predilection is reported for atypical moles.

Age

In familial atypical moles, lesions begin to develop in childhood, most frequently during the first decade of life. Lesions may not be clinically specific early on, but typical features usually develop by the end of puberty.

Atypical moles can develop throughout a person's lifetime. Atypical moles may also change or regress throughout adulthood. New or changing pigmented nevi are common in adults, and new or changing nevi in patients older than 50 years are more likely to be melanoma than in patients younger than 50 years.[29]

In one study, atypical moles in 51% of adult patients showed evidence of clinical change over time. These facts lead to the clinically challenging situation in adults as how to adequately evaluate (1) a change in a long-standing pigmented lesion or (2) the development of a new and clinically atypical lesion. An excisional biopsy should always be considered if the development of a melanoma is a concern.[30]

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Contributor Information and Disclosures
Author

Manuel Valdebran, MD Visiting Dermatopathology Fellow, University of California, San Francisco, School of Medicine

Manuel Valdebran, MD is a member of the following medical societies: International Dermoscopy Society, Medical Dermatology Society, Society for Pediatric Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

Vinod B Shidham, MD, FRCPath Professor, Vice-Chair-AP, and Director of Cytopathology, Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Center and Detroit Medical Center; Co-Editor-in-Chief and Executive Editor, CytoJournal

Vinod B Shidham, MD, FRCPath is a member of the following medical societies: American Association for Cancer Research, American Society of Cytopathology, College of American Pathologists, International Academy of Cytology, Royal College of Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Robin Travers, MD Assistant Professor of Medicine (Dermatology), Dartmouth University School of Medicine; Staff Dermatologist, New England Baptist Hospital; Private Practice, SkinCare Physicians

Robin Travers, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Informatics Association, Massachusetts Medical Society, Women's Dermatologic Society, Medical Dermatology Society

Disclosure: Nothing to disclose.

Acknowledgements

Scott M Acker, MD Associate Professor, Director of Dermatopathology, Departments of Dermatology and Pathology, University of Alabama at Birmingham

Scott M Acker, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society for Clinical Pathology, and Southern Medical Association

Disclosure: Nothing to disclose.

Steven Brett Sloan, MD Assistant Professor, Department of Dermatology, University of Connecticut School of Medicine; Residency Site Director, Connecticut Veterans Affairs Healthcare System; Volunteer Clinical Instructor, Yale University School of Medicine

Steven Brett Sloan, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Connecticut State Medical Society

Disclosure: Nothing to disclose.

Kimberly A Wenner, MD Assistant Chief of Dermatology, Madigan Army Medical Center

Kimberly A Wenner, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

References
  1. Munro DD. Multiple active junctional naevi with family history of malignant melanoma. Proc R Soc Med. 1974 Jun. 67(7):594-5. [Medline].

  2. Clark WH Jr, Reimer RR, Greene M, Ainsworth AM, Mastrangelo MJ. Origin of familial malignant melanomas from heritable melanocytic lesions. 'The B-K mole syndrome'. Arch Dermatol. 1978 May. 114(5):732-8. [Medline].

  3. Clark WH Jr, Elder DE, Guerry D 4th, Epstein MN, Greene MH, Van Horn M. A study of tumor progression: the precursor lesions of superficial spreading and nodular melanoma. Hum Pathol. 1984 Dec. 15(12):1147-65. [Medline].

  4. Annessi G, Cattaruzza MS, Abeni D, Baliva G, Laurenza M, Macchini V, et al. Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi. J Am Acad Dermatol. 2001 Jul. 45(1):77-85. [Medline].

  5. Clemente C, Cochran AJ, Elder DE, Levene A, MacKie RM, Mihm MC, et al. Histopathologic diagnosis of dysplastic nevi: concordance among pathologists convened by the World Health Organization Melanoma Programme. Hum Pathol. 1991 Apr. 22(4):313-9. [Medline].

  6. Klein LJ, Barr RJ. Histologic atypia in clinically benign nevi. A prospective study. J Am Acad Dermatol. 1990 Feb. 22(2 Pt 1):275-82. [Medline].

  7. Lebe B, Pabuççuoglu U, Ozer E. The significance of Ki-67 proliferative index and cyclin D1 expression of dysplastic nevi in the biologic spectrum of melanocytic lesions. Appl Immunohistochem Mol Morphol. 2007 Jun. 15(2):160-4. [Medline].

  8. Massi D, Naldini A, Ardinghi C, Carraro F, Franchi A, Paglierani M, et al. Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma. Hum Pathol. 2005 Jun. 36(6):676-85. [Medline].

  9. Clarke LE. Dysplastic nevi. Clin Lab Med. 2011 Jun. 31(2):255-65. [Medline].

  10. Reddy KK, Farber MJ, Bhawan J, Geronemus RG, Rogers GS. Atypical (dysplastic) nevi: outcomes of surgical excision and association with melanoma. JAMA Dermatol. 2013 Aug. 149(8):928-34. [Medline].

  11. NIH Consensus Conference. Diagnosis and treatment of early melanoma. JAMA. 1992 Sep 9. 268(10):1314-9. [Medline].

  12. Cannon-Albright LA, Goldgar DE, Meyer LJ, Lewis CM, Anderson DE, Fountain JW, et al. Assignment of a locus for familial melanoma, MLM, to chromosome 9p13-p22. Science. 1992 Nov 13. 258(5085):1148-52. [Medline].

  13. Nobori T, Miura K, Wu DJ, Lois A, Takabayashi K, Carson DA. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994 Apr 21. 368(6473):753-6. [Medline].

  14. Bale SJ, Dracopoli NC, Tucker MA, Clark WH Jr, Fraser MC, Stanger BZ, et al. Mapping the gene for hereditary cutaneous malignant melanoma-dysplastic nevus to chromosome 1p. N Engl J Med. 1989 May 25. 320(21):1367-72. [Medline].

  15. Celebi JT, Ward KM, Wanner M, Polsky D, Kopf AW. Evaluation of germline CDKN2A, ARF, CDK4, PTEN, and BRAF alterations in atypical mole syndrome. Clin Exp Dermatol. 2005 Jan. 30(1):68-70. [Medline].

  16. Chaudru V, Laud K, Avril MF, Minière A, Chompret A, Bressac-de Paillerets B, et al. Melanocortin-1 receptor (MC1R) gene variants and dysplastic nevi modify penetrance of CDKN2A mutations in French melanoma-prone pedigrees. Cancer Epidemiol Biomarkers Prev. 2005 Oct. 14(10):2384-90. [Medline].

  17. Uribe P, Wistuba II, Gonzalez S. Allelotyping, microsatellite instability, and BRAF mutation analyses in common and atypical melanocytic nevi and primary cutaneous melanomas. Am J Dermatopathol. 2009 Jun. 31(4):354-63. [Medline].

  18. [Guideline] IARC Working Group. Special Report: Policy A Review of human carcinogens- Part D: radiation. The Lancet. 2009/08. 10:751-752. [Full Text].

  19. IARC Working Group. The association of use of sunbeds with cutaneous malignant melanoma and other skin cancers: a systematic review. Int J Cancer. 2006. 120:1116-22.

  20. Tsao H, Sober AJ. Atypical melanocytic nevi. Freedburg IM, ed. Fitzpatrick's Dermatology in General Medicine. 6th ed. New York, NY: McGraw-Hill; 2003. Vol 1: 906-16.

  21. Kraemer KH, Greene MH, Tarone R, Elder DE, Clark WH Jr, Guerry D 4th. Dysplastic naevi and cutaneous melanoma risk. Lancet. 1983 Nov 5. 2(8358):1076-7. [Medline].

  22. Cooke KR et al. Dysplastic naevi in a population-based survey. Cancer. 1989. 63:1240.

  23. Bevona C, Goggins W, Quinn T, Fullerton J, Tsao H. Cutaneous melanomas associated with nevi. Arch Dermatol. 2003 Dec. 139(12):1620-4; discussion 1624. [Medline].

  24. Geller AC, Swetter SM, Brooks K, Demierre MF, Yaroch AL. Screening, early detection, and trends for melanoma: current status (2000-2006) and future directions. J Am Acad Dermatol. 2007 Oct. 57(4):555-72; quiz 573-6. [Medline].

  25. Silva JH, Sá BC, Avila AL, Landman G, Duprat Neto JP. Atypical mole syndrome and dysplastic nevi: identification of populations at risk for developing melanoma - review article. Clinics (Sao Paulo). 2011. 66(3):493-9. [Medline]. [Full Text].

  26. Marinkovic M, Janjic Z, Nikolic J. Dysplastic nevus--a risk factor of developing skin melanoma clinical and epidemiological study with retrospective review of literature. Med Pregl. 2011 May-Jun. 64(5-6):315-8. [Medline].

  27. Kanzler MH, Swetter SM. Malignant melanoma. J Am Acad Dermatol. 2003 May. 48(5):780-3. [Medline].

  28. de Snoo FA, Kroon MW, Bergman W, ter Huurne JE, Houwing-Duistermaat JJ, van Mourik L, et al. From sporadic atypical nevi to familial melanoma: risk analysis for melanoma in sporadic atypical nevus patients. J Am Acad Dermatol. May 2007. 56:748-52. [Medline].

  29. Banky JP, Kelly JW, English DR, Yeatman JM, Dowling JP. Incidence of new and changed nevi and melanomas detected using baseline images and dermoscopy in patients at high risk for melanoma. Arch Dermatol. 2005 Aug. 141(8):998-1006. [Medline].

  30. Salopek TG. The dilemma of the dysplastic nevus. Dermatol Clin. 2002 Oct. 20(4):617-28, viii. [Medline].

  31. Bronsnick T, Kazi N, Kirkorian AY, Rao BK. Outcomes of biopsies and excisions of dysplastic acral nevi: a study of 187 lesions. Dermatol Surg. 2014 Apr. 40(4):455-9. [Medline].

  32. Elder DE, Goldman LI, Goldman SC, Greene MH, Clark WH Jr. Dysplastic nevus syndrome: a phenotypic association of sporadic cutaneous melanoma. Cancer. 1980 Oct 15. 46(8):1787-94. [Medline].

  33. Roesch A, Burgdorf W, Stolz W, Landthaler M, Vogt T. Dermatoscopy of "dysplastic nevi": a beacon in diagnostic darkness. Eur J Dermatol. 2006 Sep-Oct. 16(5):479-93. [Medline].

  34. Pellacani G, Farnetani F, Gonzalez S, Longo C, Cesinaro AM, Casari A, et al. In vivo confocal microscopy for detection and grading of dysplastic nevi: a pilot study. J Am Acad Dermatol. MAR/2012. 66:e109-21. [Medline].

  35. Babacan A, Lebe B. Grade of Atypia in Dysplastic Nevi and Relationship with Dermal Fibroplasia. Turk Patoloji Derg. 2012. 28(1):17-23. [Medline].

  36. Campoli M, Fitzpatrick JE, High W, Ferrone S. HLA antigen expression in melanocytic lesions: Is acquisition of HLA antigen expression a biomarker of atypical (dysplastic) melanocytes?. J Am Acad Dermatol. 2012 Jun. 66(6):911-916.e8. [Medline].

  37. Farrahi F, Egbert BM, Swetter SM. Histologic similarities between lentigo maligna and dysplastic nevus: importance of clinicopathologic distinction. J Cutan Pathol. 2005 Jul. 32(6):405-12. [Medline].

  38. Strazzula L, Vedak P, Hoang MP, Sober A, Tsao H, Kroshinsky D. The utility of re-excising mildly and moderately dysplastic nevi: A retrospective analysis. J Am Acad Dermatol. 2014 Dec. 71(6):1071-6. [Medline].

  39. Mendese G, Maloney M, Bordeaux J. To scoop or not to scoop: the diagnostic and therapeutic utility of the scoop-shave biopsy for pigmented lesions. Dermatol Surg. 2014 Oct. 40(10):1077-83. [Medline].

  40. Comfere NI, Chakraborty R, Peters MS. Margin comments in dermatopathology reports on dysplastic nevi influence re-excision rates. J Am Acad Dermatol. 2013 Nov. 69(5):687-92. [Medline].

  41. Reddy KK, Farber MJ, Bhawan J, Geronemus RG, Rogers GS. Atypical (dysplastic) nevi: outcomes of surgical excision and association with melanoma. JAMA Dermatol. 2013 Aug. 149(8):928-34. [Medline].

  42. Duffy KL, Mann DJ, Petronic-Rosic V, Shea CR. Clinical decision making based on histopathologic grading and margin status of dysplastic nevi. Arch Dermatol. 2012 Feb. 148(2):259-60. [Medline].

  43. Tripp JM, Kopf AW, Marghoob AA, Bart RS. Management of dysplastic nevi: a survey of fellows of the American Academy of Dermatology. J Am Acad Dermatol. 2002 May. 46(5):674-82. [Medline].

  44. Somani N, Martinka M, Crawford RI, Dutz JP, Rivers JK. Treatment of atypical nevi with imiquimod 5% cream. Arch Dermatol. 2007 Mar. 143(3):379-85. [Medline].

  45. Francis SO, Mahlberg MJ, Johnson KR, Ming ME, Dellavalle RP. Melanoma chemoprevention. J Am Acad Dermatol. 2006 Nov. 55(5):849-61. [Medline].

  46. Leachman SA, Carucci J, Kohlmann W, Banks KC, Asgari MM, Bergman W. Selection criteria for genetic assessment of patients with familial melanoma. J Am Acad Dermatol. 2009 Oct. 61(4):677.e1-14. [Medline].

  47. Singh AD, Damato B, Howard P, Harbour JW. Uveal melanoma: genetic aspects. Ophthalmol Clin North Am. 2005 Mar. 18(1):85-97, viii. [Medline].

  48. Lynch HT, Fusaro RM, Lynch JF. Hereditary cancer syndrome diagnosis: molecular genetic clues and cancer control. Future Oncol. 2007 Apr. 3(2):169-81. [Medline].

 
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