Linee Guida per Lesioni della Pelle e cSCC

European Consensus-Based Interdisciplinary Guideline for Actinic Keratoses, Epithelial UV-Induced Dysplasia, and Field Cancerization

• A collaboration of multidisciplinary experts developed European recommendations for diagnosing and treating actinic keratoses (AKs) and related conditions.
• The guideline addresses epidemiology, diagnostics, risk stratification, and treatments in immunocompetent and immunosuppressed patients.
• Actinic keratoses (AKs) are potential precursors of cutaneous squamous cell carcinoma (cSCC).
• They exhibit characteristic histopathologic and immunohistochemical features of early-stage malignancy.
• AKs can progress to cSCC in situ or become invasive but this progression isn't predictable.

Introduction and Scope

• The guideline aims to assist clinicians in diagnosing and treating patients with epithelial dysplasia, including AKs.
• It considers the rising incidence of keratinocyte cancers.
• The concept of field cancerization, where genetic changes occur in the surrounding skin, has been incorporated into the recommendations.
• The guideline targets dermatologists managing patients with AKs and related conditions, emphasizing the importance of treatment and monitoring for preventing invasive skin cancers.

Definition, Epidemiology, Aetiology, and Diagnosis

• Actinic keratosis (AK) is a common cutaneous keratinocyte dysplasia involving atypical epidermal keratinocytes.
• Multiple terms exist, including solar keratosis, senile keratosis, and in situ SCC-type AK. AK may be considered precancerous or as in situ SCC.
• Field cancerization refers to subclinical changes in the surrounding skin, exhibiting similar genetic alterations to those in the visible AK lesion. It's characterized by telangiectasia, atrophy, pigmentation abnormalities, and a sandpaper-like texture.
• Epidemiological data on AK are often scarce and influenced by biases.
• Prevalence varies greatly across regions, depending on factors like UV radiation and population characteristics.
• Risk factors for AK include age >45, fair skin, light hair and eye color, freckles, a history of non-melanoma skin cancer (NMSC), sunburns, and chronic sun exposure.

Pathophysiology

• AKs primarily result from chronic sun exposure, particularly on areas with chronic sun damage.
• UVB radiation induces mutations and dysregulation of tumor suppressor genes (p53, p16INK4a, PTEN).
• Human papillomavirus (HPV) infection may act as a cofactor. Immunosuppression significantly increases the risk of AK and cSCC in individuals with HPV infections.

Clinical Features and Non-Invasive Diagnosis

• AKs typically manifest as rough, scaly skin, and can range in color from red to dark brown.
• They commonly appear on chronically sun-damaged areas.
• Dermatoscopy can aid in diagnosis, offering improved sensitivity and specificity.
• Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) can assist in differential diagnosis of AK and cSCC.
• Ancillary techniques, particularly in cases of treatment resistance, or when BCC or additional conditions are suspected, support reliable diagnosis.

Histopathologic Confirmation

• Histopathological examination is indicated in challenging cases, especially when distinguishing AK from other skin conditions, such as Bowen's disease.
• The Rowett-Hubert classification helps grade AK severity based on histological findings. However, this classification is problematic.
• Evidence suggests that hair follicle involvement correlates with the depth of invasion of associated cutaneous squamous cell carcinoma.

Treatment of Actinic Keratoses

• Treatment rationale centers on preventing transformation to invasive cSCC and managing field cancerization.
• Lesion-directed treatments target individual AK lesions, while field-directed treatments aim for widespread or subclinical AKs.
• Various approaches, including topical agents (5-fluorouracil, imiquimod, diclofenac, photodynamic therapy; PDT), cryotherapy, laser ablation, and surgical excision, help in lesion or field-directed interventions.
• Treatment selection depends on lesion characteristics, patient factors, and preferences, often requiring a case-by-case consideration.

Treatment in Immunocompromised Patients

• Immunocompromised individuals present with a higher risk of progression to invasive cSCC.
• Treatment strategies focus on field-directed approaches (e.g., PDT) over purely lesion-targeted therapies considering the common feature of extensive and multiple lesions.

Prevention and Follow-up

• Patients with AKs should be advised to practice proper sun protection, including sunscreen use, protective clothing, and limiting midday sun exposure.
• Surveillance and follow-up are crucial for detecting recurrence, new lesions, or potential progression.
• Frequency of follow-up visits should be tailored to individual risk factors, such as presence and/or extent of pre-existing keratinocyte cancers, and/or immunosuppression.

Combination Treatments

• Combined treatments enhance lesion clearance rates compared to monotherapy by utilizing multiple mechanisms of action.
• Sequential or simultaneous use of field-directed and lesion-directed therapies is often recommended for treating multiple, hyperkeratotic, and treatment-resistant AKs or extensive fields of chronic sun damage.

Photodynamic Therapy (PDT)

• PDT utilizes photosensitizing agents to selectively target and destroy atypical keratinocytes using light.
• Several versions of PDT (e.g., conventional, daylight, or laser-assisted) are mentioned.

Topical Agents

• Topical agents such as 5-fluorouracil (5-FU), imiquimod, and diclofenac provide options for AK treatment.