Dysplastic nevus pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Depending on cytologic atypia, melanocytic lesions range from dysplastic nevus to melanoma.
Pathophysiology
- Genetis play a major role in the development and density of dysplastic nevi.
- Ultraviolet light exposure playing an important modifying role.
- Activation of the oncogene BRAFV600E due to mutation is responsible for nevogenesis.
- De novo is more common cause of sporadic nevi rather than from a pre-existing nevus
- This has facilitated by have multiple driver mutations such as
- Mutations known to activate mitogen-activated protein kinases (MAPK) signaling,
- Telomerase reverse transcriptase (TERT) promoter mutations
- Hemizygous alterations of CDKN2A.
- Exome sequencing reveals that atypical nevi harbor a substantially lower mutational load than melanoma and differing ultraviolet signature mutation patterns, with cytosine to thymine transitions more frequently found in melanoma than in atypical nevi [34].
- Recurrent TERT promoter mutations have been found in a significant proportion of atypical nevi [35].
- Germline mutations of the melanoma susceptibility genes (CDKN2A, ARF, CDK4, PTEN, BRAF) have not been found in individuals with sporadic atypical mole syndrome [36].
Microscopy
- 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.[1]
- 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.[2]
- 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.[3][4]
- Such persons need to be checked regularly for any changes in their moles and to note any new ones.
Video
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References
- ↑ http://www.labpath.com/new1.html
- ↑ 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.
- ↑ 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
- ↑ 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