Keratoacanthoma

Description

• Most commonly presents as a solitary, rapidly proliferating, dome-shaped, erythematous or flesh-colored papule or nodule with a central keratinous plug, typically reaching 1 to 2 cm in diameter
• Clinically and microscopically resembles squamous cell carcinoma (SCC)
• Other presentations include grouped, multiple, keratoacanthoma (KA) centrifugum marginatum, intraoral, subungual, regressing, nonregressing, and generally eruptive (1).
• Majority are benign and resolve spontaneously, but lesions do have the potential for invasion and metastasis; therefore, treatment is required.
• Three clinical stages of KAs (1):
  • Proliferative: rapid growth of the lesion over weeks to several months
  • Maturation/stabilization: Lesion stabilizes and growth subsides.
  • Involution: spontaneous resolution of the lesion, leaving a hypopigmented, depressed scar; most but not all lesions will enter this stage.
• System(s) affected: integumentary

Epidemiology

• Greatest incidence age >50 years but may occur at any age
• Presentation increases during summer and early fall seasons.
• Most frequently on sun-exposed and hair-bearing skin but may occur anywhere
• Predominant sex: male > female (2:1)
• Most commonly in fair-skinned individuals; highest rates in Fitzpatrick skin type I to III
• 104 cases per 100,000 individuals

Etiology and Pathophysiology

• Derived from an abnormality causing hyperkeratosis within the follicular infundibulum
• Squamous epithelial cells proliferate to extend upward around the keratin plug and proceed downward into the dermis. This process is followed by invasion of elastic and collagen fibers.
• Cellular mechanism responsible for the hyperkeratosis is currently unknown. The role of human papillomavirus (HPV) has been discussed but has no established causality (2).
• Regression may be due to immune cytotoxicity or terminal differentiation of keratinocytes.
• Multiple etiologies have been suggested:
  • UV radiation
  • May be provoked by surgery, cryotherapy, chemical peels, or laser therapy
  • Viral infections: HPV or Merkel cell polyomavirus
  • Genetic predisposition: Muir-Torre syndrome, xeroderma pigmentosum, Ferguson-Smith syndrome
  • Immunosuppression
  • BRAF inhibitors (1)
  • Chemical carcinogen exposure

Genetics

• Mutation of p53 or H-ras
• Ferguson-Smith syndrome (AD)
• Witten-Zak (AD)
• Muir-Torre syndrome (AD)
• Xeroderma pigmentosum (AR)
• Grzybowski (sporadic)
• Incontinentia pigmenti (XLD)

Risk Factors

• UV exposure/damage: outdoor and/or indoor tanning
• Fitzpatrick skin type I to III
• Trauma (typically appears within 1 month of injury): laser resurfacing, surgery, cryotherapy, tattoos
• Chemical carcinogens: tar, pitch, and smoking
• Immunocompromised state
• Discoid lupus erythematosus
• HPV infection

General Prevention

Sun protection measures

Commonly Associated Conditions

• Frequently, the patient has concurrent sun-damaged skin: solar elastosis, solar lentigines, actinic keratosis, nonmelanoma skin cancers (basal cell carcinoma and SCC).
• In Muir-Torre syndrome, KAs are found with coexisting sebaceous neoplasms and malignancy of the GI and GU tracts; may have sebaceous differentiation known as a seboacanthoma