Dysplastic nevus pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Depending on cytologic atypia, melanocytic lesions range from dysplastic nevus to melanoma. The progression to melanoma usually involves the serine-threonine kinases of the MAPK/ERK pathway (mitogen-activated protein kinase) following mutation of either the N-RAS or BRAF oncogene. It is thought that the progression to melanoma requires multiple genetic mutations, where activation of the oncogene alone does not lead to the development of melanoma, and additional mutations (multiple hits), such as loss-of-function mutation of P53 tumor suppressor gene (or less commonly P16/CDKN2A or PTEN in familial cases) is required for the development of melanoma. The development of melanoma may arise de novo or from pre-existing nevi. In both cases, mutations result in dysplasia and cytologic atypia that predispose to the malignant potential of the cells. As more genes are mutated and the tumor grows, changes include the overexpression of N-cadherin, αVβ3 integrin, MMP2, MSH, cAMP, and survivin, and the loss of E-cadherin and TRMP1 proteins.




  • Most dermatologists and dermatopathologists use a system devised by the NIH for classifying melanocytic lesions.
  • In this classification, a nevus can be defined as benign, having atypia, or being a melanoma.
  • A benign nevus is read as (or understood as) having no cytologic or architectural atypia.
  • An atypical mole is read as having architectural atypia, and having (mild, moderate, or severe) cytologic (melanocytic) atypia.[2]
  • Usually, cytologic atypia is of more important clinical concern than architectural atypia.
  • Usually, moderate to severe cytologic atypia will require further excision to make sure that the surgical margin is completely clear of the lesion.\
  • The most important aspect of the biopsy report is that the pathologist indicates if the margin is clear (negative or free of melanocytic nevus), or if further tissue (a second surgery) is required.
  • If this is not mentioned, usually a dermatologist or clinician will require further surgery if moderate to severe cytologic atypia is present - and if residual nevus is present at the surgical margin.

Associated conditions

  • Atypical Mole syndrome
    • A hereditary condition which causes the person to have a large quantity of moles (often 100 or more) with some dysplastic nevi.
    • This often leads to a higher risk of melanoma, a serious skin cancer.[3]
    • A slight majority of melanomas do not form in an existing mole, but rather create a new growth on the skin.
    • Nevertheless, those with more dysplastic nevi are at a higher risk for this type of melanoma occurrence.[4][5]
    • Such persons need to be checked regularly for any changes in their moles and to note any new ones.



  1. 1.0 1.1 1.2 1.3 Miller AJ, Mihm MC (2006). "Melanoma". N Engl J Med. 355 (1): 51–65. doi:10.1056/NEJMra052166. PMID 16822996.
  2. http://www.labpath.com/new1.html
  3. Burkhart, C.G MPH, MD. Dysplastic nevus declassified; even the NIH recommends elimination of confusing terminology. SKINmed: Dermatology for the Clinician 2(1):12-13, 2003.
  4. D.J. Pope, T. Sorahan, J.R. Marsden, P.M. Ball, R.P. Grimley and I.M. Peck. Benign pigmented nevi in children. Arch of Dermatology 2006;142:1599-1604
  5. D.E. Goldgar, L.A. Cannon-Albright, L.J. Meyer, M.W. Pipekorn, J.J. Zone, M.H. Skolnick. Inheritance of Nevus Number and Size in Melanoma and Dysplastic Nevus Syndrome Kindreds. Journal of the National Cancer Institute 1991 83(23):1726-1733