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Atypical Mole (Dysplastic Nevus) Syndrome (AMS/DNS)

Basics

  • Also called dysplastic nevi syndrome (DNS), B-K mole syndrome, Clark nevi syndrome, familial atypical multiple mole melanoma (FAMMM) syndrome.
  • Characterized by numerous pigmented nevi (>50, often >100), with architectural disorder.
  • Associated with markedly increased melanoma risk, often arising de novo and at earlier ages (10–20 years earlier than sporadic melanoma).
  • Higher risk for melanomas at unusual sites (scalp, eyes, sun-protected areas).

Epidemiology

  • Prevalence: 2–8% of fair-skinned adults and those with high UV exposure.
  • Incidence uncertain due to phenotype variability and limited data.

Etiology and Pathophysiology

  • Mutations in CDKN2A gene (chromosome 9p21), encoding p16 and p14 tumor suppressor proteins.
  • CDKN2A mutations found in 25–40% of hereditary cases; autosomal dominant inheritance with variable expressivity and incomplete penetrance.
  • Sporadic atypical nevi show no clear somatic mutation patterns.

Risk Factors

  • Family history of melanoma or multiple nevi.
  • Sun exposure and history of painful sunburns.
  • Neonatal blue-light phototherapy.

Prevention

  • Primary: sun avoidance and UV protection.
  • Secondary: routine skin exams and biopsy of suspicious lesions; mitigate environmental risks.

Associated Conditions

  • Malignant melanoma, including ocular melanoma.
  • Ocular nevi.
  • Pancreatic cancer (especially in CDKN2A mutation carriers).

Diagnosis

History

  • Numerous and changing nevi (bleeding, scaling, texture changes, pigmentation alterations).
  • Congenital nevi, prior biopsies or melanoma.
  • Family history of AMS, melanoma, pancreatic cancer.
  • Immunosuppression (e.g., AIDS, chemotherapy).

Physical Exam

  • Full-body skin exam, including nails, scalp, genitalia, and oral mucosa.
  • Use ABCDE mnemonic for melanoma: Asymmetry, Border irregularity, Color variation, Diameter >6 mm, Evolving lesion.
  • “Ugly duckling sign” for identifying malignant nevi among numerous atypical nevi.
  • Dermoscopy: reticular patterns, uniform pigmentation, brown globules common; features like depigmentation, white veil, irregular homogeneity, ≥4 colors suggest melanoma.

Differential Diagnosis

  • Common/congenital nevi
  • Melanoma
  • Seborrheic keratosis
  • Dermatofibroma
  • Lentigo
  • Pigmented actinic keratosis
  • Pigmented basal cell carcinoma
  • Blue rubber bleb nevus syndrome

Diagnostic Tests

  • Dermoscopy to differentiate benign vs malignant lesions.
  • Reflectance confocal microscopy (RCM) may improve specificity.
  • Total body photography for tracking multiple nevi.
  • Biopsy of suspicious lesions: full-thickness excision with narrow margins preferred.
  • Re-excision for severe dysplasia may be considered; mild/moderate dysplasia management controversial.
  • Genetic testing (CDKN2A) is mainly research-based, not routine clinical use.

Treatment

  • No effective medications for AMS.
  • Surgical excision of all atypical nevi is not recommended due to low clinical value, poor cosmetic outcomes, and cost.
  • Biopsy or excision reserved for suspicious lesions.

Follow-Up and Ongoing Care

  • Dermatology follow-up every 6 months initially, then yearly once nevi stabilize.
  • Total body photography and dermoscopic evaluation of suspicious lesions.
  • Ophthalmologic screening for ocular nevi if familial AMS.

Patient Education

  • Counsel on sun avoidance, sunscreen use, protective clothing, and avoidance of tanning beds.
  • Teach skin self-exam using ABCDE mnemonic and “ugly duckling sign.”
  • Provide resources:
  • Verywell Health: https://www.verywellhealth.com/the-abcdes-of-skin-cancer-514388
  • Skin Cancer Foundation: https://www.skincancer.org/risk-factors/atypical-moles/
  • Melanoma Research Foundation: https://melanoma.org/melanoma-education/what-melanoma-looks-like/

Prognosis

  • Most atypical moles regress or remain stable.
  • Highest melanoma risk in those with family history and CDKN2A mutations.
  • Melanoma may arise de novo on healthy skin despite numerous atypical nevi.
  • CDKN2A mutation carriers have 60–90% melanoma risk by age 80 and 17% risk of pancreatic cancer by 75.

Complications

  • Malignant melanoma.
  • Poor cosmetic outcomes from biopsy.

References

  1. Goldsmith LA, et al. Diagnosis and treatment of early melanoma: NIH consensus panel. JAMA. 1992;268(10):1314-1319.
  2. Gaudy-Marqueste C, et al. Ugly duckling sign improves melanoma detection. JAMA Dermatol. 2017;153(4):279-284.
  3. Hofmann-Wellenhof R, et al. Dermoscopic classification of atypical nevi. Arch Dermatol. 2001;137(12):1575-1580.
  4. Salopek TG, et al. Differentiation of atypical moles from melanoma by dermoscopy. Dermatol Clin. 2001;19(2):337-345.
  5. Wiedemeyer K, et al. Dysplastic nevi: morphology and controversies. Surg Pathol Clin. 2021;14(2):341-357.
  6. Strazzula L, et al. Utility of re-excising dysplastic nevi. J Am Acad Dermatol. 2014;71(6):1071-1076.
  7. Vuong KT, et al. Surgical reexcision vs observation for dysplastic nevi: systematic review. Br J Dermatol. 2018;179(3):590-598.
  8. Duffy K, Grossman D. Dysplastic nevus: historical perspective and management. J Am Acad Dermatol. 2012;67(1):1.e1-1.e18.
  9. Helm TN, et al. Melanoma arising in persistent nevus. JAAD Case Rep. 2021;12:5-7.
  10. Dalmasso B, et al. CDKN2A mutations and melanoma survival. J Am Acad Dermatol. 2019;80(5):1263-1271.

ICD10 Codes

  • D22.9 Melanocytic nevi, unspecified
  • D22.4 Melanocytic nevi of scalp and neck
  • D22.30 Melanocytic nevi of unspecified part of face

Clinical Pearls

  • "Atypical" describes clinical appearance; "dysplastic" is a histologic term.
  • AMS increases melanoma risk, but most atypical/dysplastic nevi do not progress to melanoma.
  • Melanoma in AMS more often arises on normal skin, not from preexisting nevi.
  • Approximately 20% of familial AMS cases develop pancreatic cancer by age 75.
  • AMS patients may develop neoplasms in unusual locations including scalp, eyes, and sun-protected areas.