Atypical Mole (Dysplastic Nevus) Syndrome
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Atypical mole syndrome (AMS), also known as dysplastic nevi syndrome (DNS), B-K mole syndrome, Clark nevi syndrome, or familial atypical multiple mole melanoma (FAMMM) syndrome, is a condition characterized by a large number of pigmented nevi with architectural disorder, which arise sporadically or by inheritance and are associated with an increased risk of melanoma.
There is no consensus on criteria for AMS.
- Elevated total body nevi count, including clinically atypical nevi, is usually >50 and often >100.
- Larger number in hereditary AMS versus sporadic atypical nevi (as few as <10)
- Increased risk of melanoma
- Up to 90% occurrence by age 80 years in certain high-risk individuals
- Earlier onset than in sporadic melanoma
- More arise de novo than from an existing nevus
- Higher risk for appearance at unusual sites (e.g., scalp, eyes, and sun-protected areas)
- Median age of diagnosis for melanoma in AMS is 10 to 20 years earlier than the general population, with documented cases of melanoma as early as in the 2nd and 3rd decades of life.
Uncertain due to phenotype variability, limited data
Affects between 2% and 8% of fair-skinned adults as well as those with high exposure to ultraviolet radiation
Etiology and Pathophysiology
- Cyclin-dependent kinase inhibitor 2A (CDKN2A) mutations have been observed in familial DNS and multiple melanomas. The CDKN2A gene on 9p21 encodes for the proteins p16 and p14. p16 binds to CDK4/6 and is a negative cell-cycle regulator via inhibition of the CDK-cyclin D interaction needed for cell cycle progression from G1 to S. p14 functions by stabilizing the tumor-suppressor protein p53 in the G1 phase of the cell cycle.
- Familial cases of germline CDKN2A mutations are transmitted in an autosomal dominant fashion.
- No clear somatic mutation patterns in sporadic cases
CDKN2A gene mutation is observed in 25–40% of hereditary cases, with autosomal dominant inheritance but variable expressivity and incomplete penetrance.
Family history of melanoma or multiple nevi, sun exposure, neonatal blue-light phototherapy, history of painful sunburns
- Primary prevention with sun avoidance, sun protection
- Secondary prevention of melanoma with routine skin exams, biopsy of suspect lesions, and environmental risk mitigation as above
Commonly Associated Conditions
- Malignant melanoma, including ocular melanoma
- Ocular nevi
- Pancreatic cancer in CDKN2A mutation