Actinic Keratosis

• Potentially malignant disorder of the lips caused by long-term exposure to solar radiation. 
• Frequency is higher in geographical areas with high ultraviolet (UV) radiation, in open-air workers and in those with fairer skin types. 
• More common among individuals >50 years with long periods of exposure to solar light  but can occur at any age
• Other factors that have been associated include low educational level, a precarious socioeconomic status, genetic predisposition and unhealthy lifestyles such as smoking and poor diet 
• Rates of malignant AC transformation to squamous cell carcinoma have not been definitively established. A number of studies have estimated the rate at between 3.07% – 17%.
• Up to 95% of cases of SCC of the lips are preceded by AC 

• Most commonly affects the lower lip and presents with a broad range of clinical characteristics. 
• Initially characterized by redness, flaking, induration, erosion and/or cracks or ulcers on the vermilion. Repeated exposure to UV radiation produces chronic tissue changes including hyperkeratosis, loss of elasticity and effacement of the cutaneous-mucous labial border (Figure 1). These manifestations can be localized or diffuse.
• First clinical signs of AC can be subtle, and patients may attribute these changes to normal aging. As a result, the time to initial presentation is often delayed until more advanced changes or SCC is already present.

Herpes simplex infection, lichen planus, oral lichenoid lesions, erythema multiforme, pemphigus vulgaris, leukoplakia, SCC, basal cell carcinoma, malignant melanoma and other forms of cheilitis such as exfoliative cheilitis and contact cheilitis.

• The diagnosis of AC is based on the demographic history, clinical findings and histopathology 
• Effacement of the vermilion border is a relevant clinical characteristic but can be difficult to identify due to the loss of support of the labial structures in older patients 
• On palpation, AC is often perceived as fine sandpaper when sliding a gloved finger over the surface of the lip. Palpation is also important to differentiate AC from SCC of the lips. The neck should also be examined for the presence of lymphadenopathy (unilateral v. bilateral, mobile vs. fixed).
• Diagnosis is usually clinical, but a confirmatory biopsy should be undertaken, especially on lesions that demonstrate substantial changes, such as induration, ulceration, and suspicious of an SCC
• Histologically, AC causes changes at an epithelial level and in the underlying connective tissue. The epithelium in AC can present hyperkeratosis, hyperparakeratosis, atrophy, acanthosis or loss of polarity of the basal keratinocytes. Varying degrees of dysplasia is frequent.

Prevention

Adequate photoprotection is the important preventative measure for AC. This includes:

1. Limiting exposure to the sun between 10 am and 2 pm (or between 11 am and 3 pm in summer)
2. Wearing a protective wide-brimmed hat
3. Using water-resistant lip balm with broad-spectrum UVA and UVB protection (SPF30+), applied generously and reapplied at least every 2 hours. 

Treatmen

• Aim of treatment is to reduce the risk of malignant transformation while maintaining functionality and aesthetics. 
• Various surgical and non-surgical therapeutic options have been employed aimed at eliminating dysplastic epithelium. 
• Type of therapeutic modality should depend on the individual case and based on the clinical (size, location) and pathology findings (degree of epithelial dysplasia), taking into account side effects, potential aesthetic sequelae and evidence base

Non-Surgical Therapy

• The most common non-surgical therapies include topical applications of fluorouracil (5-FU), 5% imiquimod, 3% diclofenac with 2.5% hyaluronic acid, and 0.015% ingenol mebutate 
• Photodynamic therapy, which consists of combining a light source (400-700 nm) and a photosensitizer (5–20% 5-aminolevulinic acid or methyl aminolevulinate), produces free oxygen radicals that destabilize the membranes and cell organelles, inducing cell death
• Non-surgical therapies are less invasive and have fewer side effects than surgical modalities. However, they are less effective in terms of clinical and histological control of the lesion and associated with higher relapse rates. 
• Topical therapies can improve results when used in conjunction with surgical therapeutic options

Surgical Therapy

• Vermilionectomy by excision – should be reserved for diffuse AC with moderate to severe dysplasia
• Laser ablation – should be employed for diffuse or multisite lesions with mild dysplasia
• Cryotherapy  
• Electrocauterization

Localized lesions suspicious for malignancy should undergo excision or vaporization if moderate to severe dysplasia is detected, or complete surgical excision if an SCC is diagnosed.

Follow-up

• AC treatment should be supplemented with sun protection creams and periodic clinical reviews 
• Patients should undergo a post-therapy follow-up regimen, with visits at least every 6 months during the first 2 years and subsequently annually  
• If changes are detected during follow-up, re-biopsy should be performed, and follow-up intervals shortened.

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