Keratoacanthoma

Clinical features

• Solitary, rapidly growing (weeks), dome-shaped, flesh-coloured to red nodule with a central keratin-filled crater.
• Most common on sun-exposed skin: face, neck, dorsal hands and forearms.
• Three classical phases — proliferative (rapid growth), mature (stable), involutional (regression with scar).
• Median age 60–70; M:F ~2:1.
• Risk factors: chronic UV exposure, fair skin, HPV, immunosuppression, BRAF-inhibitor therapy (especially vemurafenib).

Histology

• Symmetrical crateriform architecture with keratin-filled invagination flanked by epithelial "lips".
• Well-differentiated keratinocytes with abundant glassy eosinophilic cytoplasm.
• Mild nuclear atypia; low mitotic count compared with conventional cSCC.
• Mixed inflammatory infiltrate at the base.
• Diagnostic limitation: superficial biopsies may not include the architecture needed to distinguish KA from cSCC; complete excision allows definitive assessment.

Multiple / syndromic forms

• Ferguson-Smith syndrome — autosomal dominant TGFBR1 mutation; multiple self-healing KAs from young adulthood; Scottish heritage.
• Grzybowski syndrome — generalised eruptive keratoacanthomas; hundreds to thousands of follicular papules; intense pruritus; very difficult to treat.
• Muir-Torre syndrome — KAs may co-exist with sebaceous neoplasms (see Muir-Torre).
• BRAF-inhibitor-induced KAs and well-differentiated cSCCs in 15–25% of patients on vemurafenib monotherapy; reduced markedly when combined with MEK inhibitor.

Management

• Surgical excision with 4–5 mm clinical margins is the standard of care for solitary KA — provides complete histology, removes diagnostic uncertainty, and prevents the long, often disfiguring resolution scar.
• For low-risk lesions in elderly / frail patients, consider:
  • Intralesional methotrexate (12.5–25 mg, repeated 2–4 weekly).
  • Intralesional 5-fluorouracil.
  • Curettage and cautery (acceptable on extremities, low-risk sites only).
• Multiple eruptive KAs — systemic acitretin, methotrexate or cyclophosphamide.
• BRAF-inhibitor associated — usually do not require dose modification; treat individually.

Prognosis

Most solitary KAs treated by excision are cured. Untreated lesions may resolve over 6–12 months but leave a depressed scar, and a small but definite proportion behave as invasive cSCC with metastatic potential — making excision the safer default. Counsel patients about UV protection and increased subsequent skin cancer risk.