What are the differential diagnoses for a skin lesion that appears to be a wart?

Differential Diagnosis of Warts

Primary Differential Diagnoses

The most critical differential diagnoses for warts include corns, calluses, actinic keratoses, squamous cell carcinoma, lichen planus, seborrhoeic keratoses, and on the feet specifically, plantar melanoma. 1, 2, 3

Corns (Heloma Durum)

• Present as hard, yellow lesions with a central translucent nucleus or plug of keratin that extends downward in a cone shape 2, 4
• Cause pain described as "walking on a small stone or pebble" 4
• Located at pressure points, typically on tips of toes or underneath metatarsal heads 2, 4
• Paring reveals a smooth translucent core WITHOUT bleeding, which is the key distinguishing feature from warts 2, 4
• Skin lines are preserved across the lesion 2

Calluses (Callosities)

• Appear as diffuse, yellowish thickening at pressure areas without a central core 2, 4
• Generally less painful than corns 4
• Paring shows homogenous thickened keratin WITHOUT bleeding 2
• Enlarge with continuing friction as a direct hyperproliferative response 4
• Skin lines remain intact 2

Actinic Keratoses

• Occur on chronically sun-exposed skin such as dorsa of hands 1, 2
• Present as discrete patches of erythema and scaling rather than hyperkeratotic papules 2
• Typically seen in middle-aged and elderly individuals 2
• Rough, sandpaper-like texture on palpation 1

Squamous Cell Carcinoma

• Must be considered in any non-healing, resistant hyperkeratotic lesion, especially in immunosuppressed patients or elderly individuals 1, 4
• May present with ulceration, bleeding, or rapid growth 1
• Biopsy is mandatory before aggressive treatment of any suspicious lesion 4
• Particularly important to exclude in pigmented plantar lesions 3

Lichen Planus

• Presents with pruritic, violaceous, flat-topped papules 1
• May have hyperkeratotic appearance on palms and soles 1
• Pruritus is a key distinguishing feature—warts are typically asymptomatic 5
• Wickham striae may be visible on close inspection 1

Seborrhoeic Keratoses

• Appear as stuck-on, waxy lesions with variable pigmentation 1
• More common in older adults 1
• Lack the disrupted skin lines characteristic of warts 1

Plantar Melanoma (Acral Lentiginous Type)

• Critical not to miss: can mimic plantar warts, especially if pigmented 3
• Presents as an enlarging, often pigmented lesion on the sole 3
• Lack of response to standard wart therapy should prompt immediate biopsy 3
• Represents a diagnostic pitfall with potentially fatal consequences if missed 3

Diagnostic Algorithm

Step 1: Visual Inspection Before Paring

• Assess skin lines (dermatoglyphics): Disrupted or absent lines suggest warts; preserved lines suggest corns or calluses 2, 4
• Look for pigmentation: Any pigmented plantar lesion warrants high suspicion for melanoma 3
• Note distribution: Pressure points favor corns/calluses; random distribution favors warts 2, 4

Step 2: Paring Test (Pathognomonic)

• Soak the lesion in warm water to soften tissue 2
• Pare down carefully with a scalpel blade, removing superficial layers 2, 4
• Pinpoint bleeding from exposed capillary loops = WART (pathognomonic) 1, 2, 4
• Translucent central core without bleeding = CORN 2, 4
• Homogenous thickened keratin without bleeding = CALLUS 2, 4

Step 3: Red Flags Requiring Biopsy

• Any lesion that fails to respond to standard therapy 4, 5
• Presence of atypical symptoms such as pruritus (suggests lichen planus or other inflammatory dermatoses) 5
• Pigmented plantar lesions, especially if enlarging 3
• Unusually severe or prolonged warts (may indicate immunosuppression or malignancy) 1
• Lesions in immunosuppressed patients (organ transplant recipients, HIV, lymphoma) 1

Special Populations and Contexts

Immunosuppressed Patients

• Warts may be large, extensive, and resistant to treatment 1
• Higher risk of HPV-associated squamous cell carcinoma, particularly with beta-papillomavirus types 1
• Lower threshold for biopsy of any atypical or non-responsive lesion 1, 5
• Unusually severe warts may be the presenting feature of underlying immune deficit (lymphoma, idiopathic CD4 lymphocytopenia, HIV) 1

Oral Cavity Lesions

• Verruca vulgaris (HPV 2,4): Well-circumscribed with prominent hyperkeratosis, white pebbly surface, occurs via autoinoculation from fingers 1
• Condyloma acuminatum (HPV 6,11): Sexually transmitted, more common in adolescents/young adults, may harbor high-risk HPV 16/18 1
• Multifocal epithelial hyperplasia (Heck disease, HPV 13,32): Multiple small papules in tight clusters giving cobblestone appearance, common in children 1
• Oral squamous papilloma: Benign proliferation requiring clinical correlation 1

Dermoscopic Features (When Available)

• Common warts: Papillomatous growth, dotted/linear vessels, hairpin-like vessels, bleeding spots 6
• Plantar warts: Papillomatous growth, bleeding spots, structureless yellowish-gray appearance 6
• Flat warts: Dotted/linear vessels, red/whitish/red-gray backgrounds 6
• Dermoscopy improves diagnostic accuracy for clinically nonclassical presentations (42% of common warts, 8% of plantar warts, 11.5% of flat warts) 6

Critical Pitfalls to Avoid

• Never assume a pigmented plantar lesion is a wart—always consider acral lentiginous melanoma and biopsy if uncertain 3
• Do not perform aggressive debridement without first ruling out neurovascular hyperkeratosis (causes severe pain and bleeding) 4
• Avoid destructive treatments on facial lesions without extreme caution due to scarring risk 2
• Do not delay biopsy of lesions with red flag features (prolonged duration, atypical symptoms, lack of response to therapy) 4, 5
• Recognize that pruritus is NOT a feature of warts—its presence suggests alternative diagnoses like lichen planus 5