Actinic Keratosis (AK)

Actinic keratosis (AK) is a precancerous skin lesion that affects sun-exposed areas. The condition presents as small, non-tender macules/papules with a characteristic sandpaper-like texture that can become erythematous scaly plaques. Actinic keratosis is usually diagnosed clinically but suspicious features warrant a biopsy to rule out invasive squamous cell carcinoma. The majority of AK lesions remain non-malignant, but it is difficult to distinguish those that will resolve from those that will become cancerous. Actinic keratosis has multiple types of treatment, including cryotherapy, shave removal, excision, topical medications, and photodynamic therapy. Lesions with features that are suggestive of cancer warrant removal and pathologic evaluation.

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Overview

Definition

  • Synonym: solar keratosis
  • Precancerous skin lesion or growth caused by sun damage

Epidemiology

  • Most common cutaneous lesion with cancerous potential (can progress to squamous cell carcinoma (SCC))
  • > 40 million people in the United States develop AK each year.
  • Men > women 

Risk factors

  • Ultraviolet (UV) radiation
    • Usually from extensive sun exposure
    • Causes mutations in keratinocytes, which prolong their survival and stimulate the proliferation of atypical cells
  • History of sunburns
  • Light skin
  • Age > 50 years
  • Immunosuppression
  • Geographic location: AK is more common in Australia than in the United States or Northern Europe due to increased sun exposure.
  • Genetic disorders
    • Xeroderma pigmentosum: 
      • Autosomal recessive condition 
      • Mutations in genes cause a defect in DNA repair mechanisms. 
      • Patients present with UV light sensitivity (e.g., severe sunburns) and skin cancer development. 
    • Bloom’s syndrome: 
      • Autosomal recessive condition (rare)
      • Caused by mutations in the BLM gene 
      • Patients present with erythematous skin rash on sun-exposed areas, small stature, immunodeficiency, and predisposition to cancer.

Clinical Presentation

Description of lesions

  • Appearance:
    • Usually < 1 cm in diameter
    • Single or multiple skin lesions
    • Tan-brown, red or flesh/skin-colored
    • Progress from small macules/papules with a sandpaper-like texture → scaly, erythematous patches/plaques
  • Areas affected (sun-exposed areas): 
    • Face and neck
    • Arms and  dorsum of hands
    • Legs
    • Bald scalp
  • Adjacent skin may show signs of solar damage (field cancerization):
    • Dry skin
    • Hyperpigmentation 
    • Telangiectasias
    • Atrophy
  • The lesions are usually asymptomatic, although tenderness, stinging sensation, or pruritus may be present.

Clinical course

  • 20%–30% of the lesions undergo spontaneous regression each year, but may reappear.
  • Some patients experience persistence of the lesions with no alterations.
  • Progression to invasive SCC:
    • Occurs in up to 20% of untreated cases
    • AK > 1 cm² (AK patch) is predictive of invasive or in situ SCC in 1½ years

Variants

  • Hypertrophic AK: thick, adherent scales (accumulation of keratin) on an erythematous base
  • Atrophic AK: a smooth, nonpalpable lesion without scale
  • Actinic cheilitis:
    • Affects the lower lip 
    • Presents as a dry, thickened, scaly papule 
    • May progress to SCC
  • AK with cutaneous horn: 
    • A benign keratinous growth that resembles a horn/cone
    • Biopsy recommended as it may transform into SCC
  • Pigmented AK:
    • Hyperpigmented macules or patches
    • Can have lateral growth and enlarge beyond 1 cm
    • Biopsy needed to distinguish from lentigo maligna

Diagnosis

Diagnosis is usually made clinically by inspection and palpation.

  • Dermoscopy:
    • Handheld device with transilluminating light source and magnifying optics
    • Primarily used to evaluate pigmented lesions
  • Biopsy: 
    • Shave biopsy: The lesion with surrounding thin layer of skin, up to the dermis, is removed. 
    • Punch biopsy: differs from a shave biopsy in that it reaches the subcutaneous layer and 3 mm is the typical diameter of the sample
    • Indications for biopsy:
      • Uncertain clinical diagnosis 
      • Suspicion of neoplasm (SCC)
        • > 1 cm in diameter
        • Induration
        • Ulceration
        • Tenderness
        • Rapid growth
        • Non-responsive to adequate therapy
      • Low threshold for immunocompromised patients
    • Histopathologic findings:
      • Cytologic atypia in the lowermost layers of the epidermis 
      • A lack of full-thickness atypia of the epidermis
      • No basement membrane invasion
      • Parakeratosis (retention of the nuclei in the stratum corneum)
      • Solar elastosis (thickened blue-gray elastic fibers in the dermis as a result of chronic sun damage)
      • Melanin in cases of pigmented AKs
      • May have coexisting melanocytic atypia

Management

Prevention

Prevention consists of the use of sunscreen and sun protection.

Treatment of head and neck lesions

  • Single or a few discrete lesions (lesion-directed therapy):
    • Cryotherapy (preferred): 
      • Use of liquid nitrogen administered by spray or contact
      • Quick, inexpensive, office-based procedure
      • Indicated for flat or hypertrophic lesions that are not suspicious for cancer
      • Use 2 freeze-thaw cycles for hypertrophic lesions.
      • Disadvantage: cannot obtain specimen for pathologic diagnosis (perform if diagnosis is clinically certain)
    • Curettage followed by electrodesiccation is used as an alternative therapy for flat lesions.
    • Shave removal followed by electrodesiccation or excision is used for hypertrophic lesions. 
      • The specimen is sent for pathologic evaluation (for lesions suspicious for cancer).
  • Multiple lesions/field cancerization (field-directed therapy):
    • Topical fluorouracil (preferred):
      • 12 times a day for 4 weeks
      • Mechanism of action: decreases cell proliferation by inhibiting thymidylate synthase
      • Causes erythema, blistering, and necrosis
      • Avoid around the eyes.
    • Topical imiquimod:
      • Applied 2 times a week for 4 months
      • Mechanism of action: produces inflammatory reaction (cytokines)
      • Causes erythema, pruritus, and erosions
      • Avoid around the eyes
    • Photodynamic therapy (PDT):
      • Application of a photosensitizer agent, aminolevulinic acid, followed by a broadband light source
      • Mechanism of action: The agent is cytotoxic when activated by light energy.
      • Causes stinging, tingling, and edema
    • Sequential treatment:
      • Used for multiple hypertrophic lesions
      • Cryotherapy is used for individual lesions followed by topical fluorouracil.

Treatment of other body sites

  • Sites with thicker skin: dorsal hands, forearm, legs
  • Sequential treatment:
    • Cryotherapy followed by topical fluorouracil
    • Gentle curettage followed by PDT

Other field-ablation treatments

  • Dermabrasion: 
    • For large areas
    • A handheld specialized instrument removes stratum corneum.
    • Painful; requires sedation and analgesia
  • Chemical peels:
    • Often used on the face
    • 35% trichloroacetic acid is applied topically.
    • Medium-depth peel causes stinging pain and visible exfoliation (up to 1 week).
  • Laser resurfacing: multiple treatments required

Differential Diagnosis

  • Squamous cell carcinoma: a cutaneous malignancy most commonly found in sun-exposed sites. Unlike AK, the atypical cells of in situ carcinoma involve the entire thickness of the epidermis, and invasive SCC invades beyond the basement membrane.
  • Seborrheic keratosis: a benign neoplasm consisting of immature keratinocytes occurring commonly in the elderly. A seborrheic keratosis usually has a sharply demarcated, round, stuck-on appearance on the skin.
  • Basal cell carcinoma (BCC): a malignant skin tumor arising from the basal cell layer of the epidermis. Basal cell carcinoma is the most common skin cancer, and usually presents as slowly growing “pearly papules” with telangiectasia (prominent, dilated subepidermal blood vessels). 
  • Seborrheic dermatitis: a chronic inflammatory dermatosis characterized by the presence of greasy, red (inflamed) skin lesions affecting the scalp (as dandruff), posterior aspect of the neck, and the forehead. The etiology is uncertain, but the condition appears to be linked to increased sebum production and possibly colonization of the skin by fungi of the genus Malassezia

References

  1. Berman, B., Dellavalle, R., Robinson, J., Corona, R.(2020). Treatment of actinic keratosis. UpToDate. Retrieved 13 Sept 2020, from https://www.uptodate.com/contents/treatment-of-actinic-keratosis
  2. Lazar, A. (2020). The Skin  in Kumar, V.Abbas, A., Aster, J. (Eds.), Robbins and Cotran Pathologic Basis of Disease (10th ed., pp. 1133-1170). Elsevier, Inc.
  3. Padilla, R., Robinson, J., Corona, R. (2019). Epidemiology, natural history and diagnosis of actinic keratosis. UpToDate. Retrieved 13 Sept 2020, from https://www.uptodate.com/contents/epidemiology-natural-history-and-diagnosis-of-actinic-keratosis
  4. Spencer, J., James, W. (2020). Actinic Keratosis. Medscape. Retrieved 13 Sept 2020, from https://emedicine.medscape.com/article/1099775-overview

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