Actinic Keratosis (AK)

Keratinocytic intraepidermal neoplasia (KIN), solar keratosis, senile keratosis, keratoma senile, precancerous keratosis, in situ squamous cell carcinoma (SCC in situ).

UV-induced intraepidermal keratinocytic dysplasia. Increasingly recognized by dermatopathological societies (e.g., WHO, EADV) as early SCC in situ, especially high-grade (KIN II–III) lesions.

• Most common premalignant lesion in sun-exposed skin.
• Prevalence in Europe: ~15 % in men, ~6 % in women; >70 years: ~34 % in men, ~18 % in women.
• Particularly frequent in outdoor workers and immunosuppressed persons.
• Often occurs as part of field cancerization.
   

Histologic grading (Röwert Huber):

• KIN I: basal layer atypia
• KIN II: atypia in lower 2/3 of epidermis
• KIN III: full-thickness atypia = SCC in situ
• International guideline bodies now often reclassify AKs, especially KIN II–III, as SCC in situ. 
• Olsen grading is considered clinically less relevant.

Clinical Variants

• Classical erythematous AK
• Hypertrophic/hyperkeratotic AK
• Atrophic or bowenoid AK
• Pigmented, lichenoid variants and actinic cheilitis
   

• Cumulative UVB exposure → TP53, NOTCH1, and other mutations, causing keratinocyte dysplasia.
• Risk factors: fair skin, immunosuppression (100–250 fold risk in transplant recipients), xeroderma pigmentosum, possible cofactor role of HPV.
• Inflammatory microenvironment and field cancerization contribute to lesion progression and cluster formation.

• Sharply marginated, scaly erythematous macule/papule/plaque
• Texture: rough (“sandpaper”)
• Usually asymptomatic; sometimes mild pruritus or burning
• Common sites: forehead, scalp (esp. bald areas), ears, nose, lips, dorsal hands, forearms
• Cutaneous horn (cornu cutaneum) in hypertrophic variants, with elevated malignant risk

• Clinical inspection and palpation are essential
• Dermoscopy: “strawberry pattern” (red pseudo-network with white scale)
• Biopsy if lesions are hypertrophic, tender, or persist: to exclude invasive SCC
• Histology: parakeratosis, keratinocyte atypia, solar elastosis, loss of normal epidermal architecture

Sun-exposed regions: face, bald scalp, ears, neckline, lips, dorsal hands, forearms.

Chronic sun exposure, outdoor work, history of sunburns, fair skin. Transplant patients typically have multiple and treatment-resistant AKs.

• Dysplastic keratinocytes (notably in basal and lower epidermal layers), parakeratosis, solar elastosis
• Full-thickness atypia in KIN III (SCC in situ)
• Invasion beyond BM indicates cSCC

• ~10 % of AKs progress to invasive SCC (range 0.1–20 %)
• ~60 % of cutaneous SCCs arise from prior AKs
• Spontaneous regression in up to 30 %; ~50 % recurrence within 12 months
• Risk increased in hypertrophic AKs, immunosuppression, and in field cancerization

• Avoid sun exposure, especially 11 am–3 pm
• Use UV-protective clothing and broad-spectrum sunscreen (SPF ≥ 50)
• Regular skin checks in high-risk individuals
• Retinoids can be considered for chemoprevention in immunosuppressed patients

Favorable with early diagnosis and treatment. Field cancerization mandates ongoing surveillance. Untreated AKs may progress to SCC.

1. Stockfleth et al. Field cancerization in AK. JEADV. 2023;37(2):210–221.
2. Dirschka et al. AK treatment options. J Clin Aesthet Dermatol. 2022;15(1):S11–24.
3. Piaserico et al. Reclassifying AK as SCC in situ. Br J Dermatol. 2022;187(4):509–516.
4. Blauvelt et al. Phase III tirbanibulin trials. N Engl J Med. 2021;384(6):512–520.
5. Bhatia et al. Safety/tolerability over 100 cm². JAAD Int. 2024;17:6–14.
6. Dao et al. Tirbanibulin 1 % ointment review. Ann Pharmacother. 2022;56(4):494–500.
7. Real-world Italian study: 51 % total clearance. Int J Dermatol. 2024.
8. Schmitz et al. AI risk prediction in AK. Skin Res Technol. 2023;29(5):e13321.