What is the appropriate evaluation and management for a cafe‑au‑lait macule in a patient residing on the coast of Maine?

Evaluation and Management of Café-au-Lait Macules

The term "coast of Maine" refers to café-au-lait macules with irregular, jagged borders—these lesions respond significantly better to laser treatment than smooth-bordered lesions, but more importantly, this morphologic feature does not predict underlying genetic syndromes and should not influence your diagnostic workup. 1

Understanding the "Coast of Maine" Terminology

The "coast of Maine" versus "coast of California" classification describes border morphology of café-au-lait macules:

• Coast of Maine: Irregular, jagged, ill-defined borders 1
• Coast of California: Smooth, well-defined borders 1

This distinction is relevant only for laser treatment response—coast of Maine lesions achieve 76-100% clearance versus 26-50% for coast of California lesions. 1 However, border morphology does not correlate with the presence or absence of neurofibromatosis type 1 (NF1) or other genetic syndromes. 1

Primary Clinical Priority: Rule Out NF1 and Other Genetic Syndromes

Your immediate focus should be determining whether this patient has NF1 or another genetic syndrome, as NF1 reduces life expectancy by 8-15 years due to malignant peripheral nerve sheath tumors and cardiovascular disease. 2

Step 1: Document and Count All Café-au-Lait Macules

• Measure and count every café-au-lait spot on the entire body 2
• ≥6 café-au-lait macules ≥5 mm in prepubertal children meets one NIH diagnostic criterion for NF1 2, 3
• Border morphology (coast of Maine vs. California) does not affect this assessment 1

Step 2: Perform Targeted Physical Examination

Examine specifically for these features:

• Axillary or inguinal freckling (Crowe's sign): Highly specific for NF1, typically appears within first 3 years of life 2, 3
• Cutaneous or subcutaneous neurofibromas: Palpate entire skin surface 2
• Lisch nodules: Requires slit-lamp examination by ophthalmology 2, 3
• Plexiform neurofibromas: May be subtle in infancy but often congenital 2
• Darier's sign: Rub the lesion—positive urtication suggests mastocytoma, not café-au-lait macule 2

Look for features suggesting alternative diagnoses:

• Dysmorphic facial features + congenital heart defects + short stature + cryptorchidism: Suggests RASopathies (Noonan, Costello, CBL syndromes) 2, 3
• Hypopigmented macules + pilomatrixomas + family history of childhood cancers: Suggests Constitutional Mismatch Repair Deficiency (CMMRD) with extremely high cancer risk 2, 4
• Microcephaly + dysmorphic features + growth deficiency + immunodeficiency: Suggests Nijmegen Breakage Syndrome 2

Step 3: Obtain Three-Generation Family History

Specifically ask about:

• Café-au-lait macules in family members 3, 4
• Neurofibromatosis diagnosis 3
• Childhood cancers (leukemia, brain tumors, GI malignancies) 2, 4
• Learning disabilities or developmental delays 3

Step 4: Determine Referral Needs

Immediate genetics referral if:

• ≥2 NIH criteria for NF1 are met 3, 4
• Developmental delays, hypotonia, or neurologic symptoms present 3, 4
• Family history of childhood cancers 2, 4
• Café-au-lait macules + childhood leukemia or brain tumor 4

Pediatric dermatology referral if:

• Large or giant congenital melanocytic nevus identified (raised, hairy, verrucous lesions) 2

Specialized NF1 clinic referral if:

• NF1 confirmed or highly suspected 4

Surveillance Protocol Based on Findings

If Single Café-au-Lait Macule with No Other Features

• Clinical review every 3-6 months during first 3 years of life 2
• Annual visits after age 3-5 years if no additional features develop 3
• Educate parents to monitor for new freckling, skin lumps, vision changes, developmental concerns 3

If Multiple Café-au-Lait Macules but <6 or <5mm

• Close follow-up every 3-6 months during first 3 years 3
• Annual examination after age 3-5 years 3
• Consider genetics referral if any additional features emerge 3

If NF1 Confirmed or Suspected

• Annual comprehensive examination including blood pressure monitoring and neurologic assessment 2, 4
• Lifelong surveillance required due to 8.5% MPNST risk by age 30,15.8% by age 85 4
• Women: annual mammography starting age 30, consider breast MRI ages 30-50 4

Critical Pitfalls to Avoid

Do not assume a single large café-au-lait macule is benign—it may represent early McCune-Albright syndrome or other conditions requiring evaluation. 2

Do not confuse Legius syndrome with NF1—Legius patients have café-au-lait macules and freckling but lack neurofibromas, optic gliomas, and tumor risks, with normal life expectancy. 2, 4

Do not delay referral when café-au-lait macules accompany developmental delay, hypotonia, or childhood leukemia—these suggest high-risk syndromes like CMMRD requiring immediate genetics evaluation. 2, 4

Do not dismiss border morphology as diagnostically irrelevant for laser treatment—if the patient desires cosmetic treatment, coast of Maine lesions achieve excellent response (76-100% clearance) versus poor response (26-50%) for coast of California lesions. 1

Do not perform routine CT imaging for cancer screening in NF1—annual clinical examination is the cornerstone of surveillance, with symptom-directed MRI (not CT) when imaging is indicated to minimize radiation exposure. 4

Key Distinction: 19.5-57.1% of Patients with Multiple Café-au-Lait Macules Do Not Have NF1

Recent evidence demonstrates that a significant proportion of patients presenting with isolated café-au-lait macules do not develop NF1 after follow-up or genetic testing. 5 This underscores the importance of:

• Not assuming NF1 diagnosis based solely on café-au-lait macules 5
• Distinguishing definitive NF1 (requires café-au-lait macules PLUS Lisch nodules, neurofibromas, bone dysplasia, optic glioma, or family history) 5
• Considering genetic testing to guide follow-up when diagnosis is uncertain 5