eMedicine Specialties > Dermatology > Benign Neoplasms
Atypical Mole (Dysplastic Nevus)
Updated: Nov 20, 2008
Introduction
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, Munro1 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 al2,3 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
Atypical moles differ from common acquired melanocytic nevi in several respects, including diameter and lack of pigment uniformity. Unfortunately, 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 follows9 :
- 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)
For additional information on malignant melanoma, see Malignant Melanoma. Additionally, the Medscape Skin Cancer Resource Center and Melanoma Resource Center may be helpful.
Pathophysiology
Atypical moles can be inherited or sporadic. Formal genetic analysis has suggested an autosomal dominant mode of inheritance. Unfortunately, genetic studies have not shown consistent data.
Germline mutations in 3 genes, CDK2NA10 and CDK4,11 mapped to 9p21 and 12q14, and CMM1, mapped to 1p,12 have been linked to a subset of hereditary melanomas and FAMM syndrome. In addition, somatic mutations in PTEN, BRAF,13 and MCR1 (melanocortin-1 receptor)14 have been associated with melanoma. Unfortunately, studies have found no alterations in these genes in some patients with FAMM syndrome, 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. 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.
Frequency
United States
The prevalence of atypical moles in white populations has been reported to be as high as 17%.15 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.16
International
In Australia and New Zealand, the prevalence of atypical moles has been reported to be 5-10%.17 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.18 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.19 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.
- 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%.20
- 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.16,21 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.22
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.23
Clinical
History
A detailed personal and family history should be obtained, with special attention regarding moles and melanomas.
Atypical moles may arise anytime during a patient's lifetime. Atypical moles can change over time, and new lesions may develop. Individuals with FAMM may have 1 to several hundred atypical moles, whereas those with nonfamilial (sporadic) atypical moles typically have only 1-10 lesions, although they may also present with several hundred lesions.
An individual with atypical moles who is from a family prone to melanoma has a high lifetime risk of developing a melanoma. Rapid and characteristic changes should prompt consideration for excision/biopsy to rule out melanoma.
Physical
Patients with FAMM syndrome should have a complete cutaneous examination performed at the first office visit and then at least every 12 months for life.
Atypical moles often have a characteristic appearance, although individual lesions may not show all the findings. Typically, they are large pigmented lesions and frequently measure 5-15 mm in diameter. Atypical moles are usually larger than common moles. Borders are usually irregular, notched, and ill defined. Macular and papular areas may be present within a single lesion (also described as a "fried egg" appearance). Color is highly variable and ranges from tan to dark brown to pink.15
Atypical moles may appear anywhere on the body, but they most frequently occur on the back, the chest, the buttocks, the breasts, and the scalp. Lesions can be found in sun-exposed and sun-protected areas. Patients with FAMM syndrome may have more than 100 lesions, which is far greater than the average number of common moles (<50) in most individuals.
Although the diagnosis of an individual atypical mole may be clinically simple, patients often have many nevi, which may make monitoring complex. An excisional biopsy should be considered in the initial evaluation of atypical mole for histologic confirmation of dysplastic nevi versus melanoma. Shallow scoop saucerizations including at least a 2-mm margin of clinically normal skin surrounding the pigmented lesion can be performed if the lesion is removed entirely and care is taken for adequate depth for accurate staging in melanoma.
Causes
Atypical mole may be inherited (FAMM syndrome) or appear sporadically.24 Sun exposure may play a part in the distribution patterns of these nevi, but it is not absolutely necessary because atypical moles also appear on sun-protected skin. Patients with FAMM syndrome are at an increased risk for the development of melanoma, although the individual risk is variable.
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References
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Further Reading
Keywords
AM, active junctional nevi, atypical melanocytic nevi, B-K mole, Clark's nevi, dysplastic nevi, dysplastic mole
