How do you differentiate between melanonychia and subungual melanoma in adult patients, particularly those with a history of sun exposure, light skin, or a family history of skin cancer, presenting with suspicious nail pigmentation?

Differentiating Melanonychia from Subungual Melanoma

Suspicious nail pigmentation in adults requires urgent dermatology referral for nail matrix biopsy, as subungual melanoma has only 43% 10-year survival and a mean diagnostic delay of 2 years. 1

High-Risk Clinical Features Requiring Urgent Biopsy

Any adult presenting with new or changing melanonychia should be considered for urgent specialist evaluation, particularly those with the following features:

• Width >28-30% of the nail plate (strongest predictor of malignancy) 2, 3
• New pigmented line appearing in adulthood (benign melanonychia is typically congenital or develops in childhood) 1
• Irregular borders or multicolor variation within the pigmented band 1, 2, 3
• Progressive change in size, shape, or color over time 1
• Extension of pigmentation onto periungual skin (Hutchinson's sign or micro-Hutchinson's sign on dermoscopy) 1, 3
• Associated nail plate dystrophy, ulceration, or nodule formation 1, 2
• Width greater than 3mm or involving multiple digits asymmetrically 1
• Subungual hyperkeratosis (newly recognized feature significantly associated with melanoma) 3

Patient-Specific Risk Stratification

Adults with light skin, sun exposure history, or family history of skin cancer presenting with melanonychia warrant heightened suspicion, as subungual melanoma patients are typically older (median age 56 years for melanoma vs. 31 years for benign lesions) 2. The big toe requires particular vigilance, as it is the most common site for subungual melanoma 1.

Dermoscopic Evaluation

Onychoscopy provides critical diagnostic information and should be performed before biopsy decision-making:

• Malignant features: Granular pigmentation, multicolor presentation, irregular lines with varying width/spacing, micro-Hutchinson's sign, and subungual hyperkeratosis 3
• Benign features: Regular parallel lines, uniform color, consistent band width 3

However, dermoscopy alone cannot definitively exclude melanoma and should not delay biopsy in suspicious cases 4.

Histopathologic Differentiation

Melanocyte density is the most objective discriminator between benign and malignant lesions 5:

• Invasive melanoma: Mean melanocyte count 102 per 1mm of dermo-epithelial junction (range 52-212) 5
• Melanoma in situ: Mean melanocyte count 58.9 (range 39-136) 5
• Benign subungual lentigo: Mean melanocyte count 15.3 (range 5-31) 5
• Normal nail apparatus: Mean melanocyte count 7.7 (range 4-9) 5

Additional malignant histologic features include confluent stretches of solitary melanocytes, multinucleated melanocytes, lichenoid inflammation, and florid pagetoid spread 5.

Mandatory Referral and Biopsy Protocol

Refer urgently to a dermatologist with expertise in nail apparatus biopsy—suspicious nail lesions should never be biopsied in primary care 1, 6. The complexity of nail anatomy and the fact that melanoma arises in the nail matrix requires specialized technique 7.

Proper biopsy technique is non-negotiable 7, 6:

• Remove the nail plate sufficiently to expose the underlying lesion 7, 6
• Sample the nail matrix adequately, as this is where melanoma originates 7, 6
• Perform excisional biopsy when feasible, encompassing the entire lesion 6
• Use incisional biopsy for larger lesions, ensuring adequate matrix sampling 6

Critical Pitfalls to Avoid

Never perform superficial shave biopsy of suspected melanoma, as this underestimates Breslow thickness and clinical stage 7, 6. Do not delay referral for "watchful waiting" in adults with new or changing melanonychia 1. The mean diagnostic delay of 2 years for subungual melanoma directly impacts the poor 43% 10-year survival rate 1.

Do not assume fungal infection without mycological confirmation, particularly in single-nail involvement without associated skin infection 1. While onychomycosis commonly affects the big toenail, empiric antifungal treatment before establishing diagnosis can delay critical melanoma detection 1.

Do not proceed with biopsy without adequate nail plate removal when the underlying lesion needs visualization 6. Inadequate sampling is a common cause of misdiagnosis, as biopsies of periungual lesions are frequently misinterpreted due to the three-dimensional nail bed anatomy 7, 8.

Differential Diagnosis Considerations

While subungual melanoma is the critical diagnosis to exclude, other causes of melanonychia include 1:

• Onychomycosis (requires mycological confirmation with KOH and culture)
• Bacterial infection (Pseudomonas aeruginosa causing green/black discoloration)
• Chronic trauma (particularly to the big toe)
• Psoriasis (with associated nail dystrophy)
• Lichen planus (pigmentation changes in ~10% of cases)

However, in adults with new or changing pigmentation, malignancy must be excluded first through appropriate specialist evaluation and biopsy 1.