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Subject: Dysplastic Nevus Syndrome
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Condition resulting in elevated total body nevi count, including clinically atypical nevi
Usually >50, although often >100
Larger number in hereditary DNS versus sporadic dysplastic nevi (DN) (as few as <10 in sporadic, although high numbers also possible)
Increased risk of melanoma (1)
Up to 90% occurrence by age 80 years in certain high-risk individuals
Earlier onset than sporadic melanoma cases
Most arise out of healthy skin as opposed to a preexisting atypical nevus
Higher risk for appearance at unusual sites (e.g., scalp)
DNS terminology often used interchangeably with AMS, familial atypical multiple mole melanoma (FAMMM) syndrome, and B-K mole syndrome
Median age of diagnosis for melanoma is 10–20 years earlier than the general population, with documented cases of melanoma as early as in the early teens and 20s (2).
Melanomas in the setting of DNS are most often superficial spreading or nodular type.
Unclear for sporadic cases, although somatic p16 inactivation noted in 40% of familial melanoma
Familial cases of germline CDKN2A mutations considered to be transmitted genetically in an autosomal dominant fashion.
Autosomal dominant inheritance in hereditary cases but variable expressivity and incomplete penetrance
CDKN2A mutation observed in 25–40% of hereditary cases
No currently available prevention strategies
Treatment is directed toward secondary prevention of melanoma complications with routine skin exams, biopsy of suspect lesions, and environmental risk mitigation (e.g., sun protection and sun avoidance).
Experimental early detection protocols for pancreatic cancer in use with some high-risk individuals
Malignant melanoma, including ocular melanoma
Pancreatic cancer in CDKN2A mutation
Changing lesions: bleeding, scaling, size, texture, nonhealing, hyper- or hypopigmentation
Prior skin biopsies
In 1st- or 2nd-degree relatives
ABCDE mnemonic for pigmented lesions: Asymmetry, Border irregularity, Color variegation, Diameter >6 mm, and Evolving lesion
Melanoma typically with several characteristics of ABCDEs on gross exam (DN often defined as ≥5 mm + at least 2 other features)
Difficult differentiating DN from melanoma using these criteria
“Ugly duckling sign” (5)
Melanoma screening strategy of identifying atypical nevi straying from the predominant nevus pattern when numerous atypical nevi present.
Most common features of DN on dermatoscopy magnification per the pattern analysis method include the following (6):
Atypical pigment network
Irregular/peripheral depigmentation areas
Irregular distribution of brown globules
Pigmentation with central heterogeneity and abrupt termination
Some dermatoscopic features more suggestive of melanoma include the following (6):
Homogenous areas distributed irregularly, in multiple areas, or >25% of total lesion
Acquired melanocytic nevi
Sporadic atypical nevi
Pigmented actinic keratosis
When the total nevus count is high and individually following each nevus impractical, total-body photography may aid in the evaluation of evolving nevi as well as in documenting new nevi (8)[C].
Further exam of nevi with a dermatoscope may help in distinguishing between benign and malignant pigmented lesions.
Biopsy is recommended of any new lesion where melanoma cannot be excluded or for any existing evolving lesion concerning for melanoma.
Preferred method entails full-thickness biopsy of the entire lesion with a narrow 2-mm margin of normal skin by excisional, incisional, or punch biopsy (8)[C].
Excisional biopsy provides the most accurate diagnosis and should be performed when possible.
Take care to provide a sufficiently deep sample down to the fat to allow assessment of the depth of any melanomas.
Scoop shave biopsy including a sufficient lateral and deep margin can also be used, but care must be taken to not transect the deep margin.
Referral to a dermatologist for routine skin exam
Consider referral to a specialty pigmented lesion clinic.
Ophthalmologic exams for ocular nevi/melanoma screening
Oncology or specialized genetics study group involvement if strong family predisposition to pancreatic cancer
Possible cosmetic surgery consultation for cosmetically poor excision outcomes
Topical chemo- and immunotherapies therapies have been unsuccessfully attempted to treat atypical nevi.
Laser treatment should be avoided because it is both unsafe and ineffective for melanocytic nevi.
Total body skin exam (including nails, scalp, genital area, and oral mucosa) every 3–6 months initially, starting at puberty; may be reduced to annually once nevi are stable.
Dermatoscopic evaluation for suspect lesions
Ocular exam for those with familial DNS
Excision of suspect lesions
Total body photography at baseline
Monthly self-exams of skin
Sun avoidance and sun protection
Teach patients the “ABCDE” mnemonic + “ugly duckling sign” for assessing nevi and identifying potential melanomas.
Encourage sun protection/minimization of sun exposure.
Educate on sun avoidance, proper application of sunscreen, use of protective clothing (e.g., hats), and avoidance of tanning booths.
Provide instruction on skin self-exam techniques.
A sample listing of patient-centric review sources on this topic are as follows:
American Academy of Dermatology (http://www.aad.org/dermatology-a-to-z/diseases-and-treatments/m---p/moles/who-gets-types)
Skin Cancer Foundation (http://www.skincancer.org/skin-cancer-information/dysplastic-nevi)
Melanoma Research Foundation (http://www.melanoma.org/learn-more/melanoma-101/what-melanoma)
Multiple classification schemes have been developed over the years to delineate risk of melanoma in patients with DNS. Individuals with a family history of melanoma are at greatest risk. A classification system developed by Rigel is simply and readily applied in the clinical setting. Points are assigned based on incidence of melanoma, with 1 point given for a personal history with melanoma, and 2 points for each family member with melanoma (modified nuclear family consisting of 1st-degree relatives + grandparents and uncles/aunts) and stratified as follows (9):
Score = 0, Rigel group 0, 6% 25-year accumulated risk for melanoma
Score = 1, Rigel group 1, 10% risk
Score = 2, Rigel group 2, 15% risk
Score ≥3, Rigel group 3, 50% risk
The CDKN2A mutation has also been associated with a 60–90% risk of melanoma by age 80 years and a 17% risk for pancreatic cancer by age 75 years.
Poor cosmetic outcomes from biopsy
Czajkowski R, Placek W, Drewa G, et al. FAMMM syndrome: pathogenesis and management. Dermatol Surg. 2004;30(2, Pt 2):291–296. [View Abstract]
Farber MJ, Heilman ER, Friedman RJ. Dysplastic nevi. Dermatol Clin. 2012;30(3):389–404. [View Abstract]
Friedman RJ, Farber MJ, Warycha MA, et al. The “dysplastic” nevus. Clin Dermatol. 2009;27(1):103–115. [View Abstract]
Moloney FJ, Guitera P, Coates E, et al. Detection of primary melanoma in individuals at extreme high risk: a prospective 5-year follow-up study [published online ahead of print June 25, 2014]. JAMA Dermatol. doi:10.1001/jamadermatol.2014.514.
Naeyaert JM, Brochez L. Clinical practice. Dysplastic nevi. N Engl J Med. 2003;349(23):2233–2240. [View Abstract]
Robson ME, Storm CD, Weitzel J, et al. American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2010;28(5):893–901. [View Abstract]
Slade J, Marghoob AA, Salopek TG, et al. Atypical mole syndrome: risk factor for cutaneous malignant melanoma and implications for management. J Am Acad Dermatol. 1995;32(3):479–494. [View Abstract]
D23.9 Other benign neoplasm of skin, unspecified
D23.4 Other benign neoplasm of skin of scalp and neck
216.9 Benign neoplasm of skin, site unspecified
216.4 Benign neoplasm of scalp and skin of neck
254818000 Dysplastic nevus of skin (disorder)
254819008 atypical mole syndrome (disorder)
Melanoma in DNS tends to arise from healthy skin despite a large number of atypical nevi.
~20% of individuals with familial DNS will develop pancreatic cancer by age 75 years.
Patients with DNS tend to produce neoplasms in unusual sites such as the scalp, eyes, and double sun-protected areas (e.g., gluteal folds).
~10% of melanomas are featureless on dermatoscopy.