Actinic keratosis

Meet the patient

A 72-year-old man complains that his bald scalp feels "rough, like sandpaper" when he runs a hand over it. On inspection you see half a dozen pink, scaly macules scattered across a field of weathered, telangiectatic, mottled skin. One lesion on the crown has thickened and grown tender over the last two months.[1][6]

The rough scalp is the textbook AK field — and it carries two lessons in one. The scattered gritty macules are field cancerization, to be treated as a field; the one lesion that has thickened and turned tender is the red flag that needs a biopsy, because it may already have crossed into invasive SCC. Hold those two ideas — treat the field, biopsy the thickened — and you have the whole topic.[1]

What AK is — a premalignant lesion, never just a "sun spot"

Actinic keratosis is intraepidermal keratinocyte dysplasia on chronically sun-damaged skin — the commonest premalignant lesion we see, and the earliest clinically detectable stage of the continuum that runs through SCC in situ (Bowen's disease) to invasive SCC. It is not a harmless age spot; it shares its driver mutations with the SCC it can become.[6]

The single concept that changes management is field cancerization. Each visible AK is the tip of an iceberg: the surrounding sun-damaged skin harbours multiple independent premalignant clones, each from a separate UV hit, that are clinically silent today but will surface as new lesions tomorrow. This is why treating only the visible spots fails — new AKs keep emerging from the damaged field unless the whole field is treated.[1]

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How common, who, and where

AK is the most frequently encountered premalignant lesion in dermatology and primary care, and prevalence rises steeply with age, cumulative UV and fair skin. Because it is asymptomatic and hides within background sun damage, the true burden is higher than the clinical detection rate.[1]

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Prevalence is fiercely latitude-dependent — Australia and New Zealand top the list, sun-belt US states trail them, and Northern Europe carries a smaller but still substantial burden in elderly fair-skinned people. The risk-factor list groups cleanly:[1][6]

• Intrinsic: fair skin, light eyes, red or blonde hair (Fitzpatrick I–II), poor tanning with a tendency to burn, advancing age, male sex (more occupational sun, less protection), and DNA-repair disorders — above all xeroderma pigmentosum.
• Environmental: cumulative UV is the dominant exogenous cause (UVB 290–320 nm plus UVA); outdoor occupation or recreation at low latitude or high altitude; tanning beds.
• Iatrogenic and comorbid: immunosuppression — solid-organ transplantation and chronic lymphocytic leukaemia above all; chronic PUVA; ionising radiation or arsenic; a prior cutaneous SCC or extensive AK burden. [1]

The molecular story — UV, p53, and the field

UV-induced DNA damage is the initiating event. UVB is directly absorbed by DNA, forming cyclobutane pyrimidine dimers and 6-4 photoproducts; the signature mutations are C to T and CC to TT transitions at dipyrimidine sites. Normally the nucleotide-excision-repair (NER) pathway removes the dimers, but cumulative UV and advancing age erode NER capacity — and in xeroderma pigmentosum, defective NER produces a catastrophic childhood burden of AK and NMSC.[1]

The TP53 tumour-suppressor gene is mutated in about 50–80 percent of AK lesions. In a healthy keratinocyte, wild-type p53 arrests the cell cycle after UV damage and directs damaged cells into apoptosis. A UV-induced p53 mutation abolishes that checkpoint, letting the mutated keratinocyte survive, proliferate and found a clone of atypical cells in the lower epidermis.[8]

Other recurrent alterations — NOTCH1, CDKN2A, RAS — are the same drivers seen in invasive SCC, which is molecular evidence that AK and SCC share a lineage. The progression is histological:[1]

Recognise the lesion — and the variants that change the plan

AKs are rough, scaly, erythematous macules or patches that are "easier felt than seen." The gritty, sandpaper texture on palpation is often the first clue, even when the erythema is subtle. Patients seldom volunteer symptoms and often put the roughness down to dry skin.[1]

Typical morphology: 2–10 mm, sometimes coalescing into larger patches; pink to red with a yellow-brown scale, occasionally brown-grey when pigmented; dry, adherent scale that can be picked off leaving an erythematous base; often asymptomatic, with mild itch, tenderness or burning after sun exposure. Distribution is the sun-exposed sites — bald scalp, face (forehead, nose, cheeks), ears, dorsal hands, forearms, and the vermilion of the lower lip.[1]

Variants you must name, because thickness and site change management:[1]

• Classical or hypertrophic AK — the commonest; a rough, adherent yellow-brown scale on an erythematous base. Hypertrophic lesions are thicker, harder to clear with a brief freeze, and more likely to hide invasive SCC — biopsy when the scale is markedly adherent or the lesion is indurated.
• Atrophic AK — a flat, pink-red macule with minimal scale; easily missed on inspection and found by palpation, often mistaken for rosacea, telangiectasia or a scar.
• Pigmented AK — brown to grey-brown with scale; distinguish from solar lentigo, lentigo maligna and seborrhoeic keratosis on dermoscopy.
• Actinic cheilitis — AK of the lower-lip vermilion: blurred vermilion border, scaling, fissuring, atrophy, pallor or erythema. Higher malignant potential than cutaneous AK — closer surveillance, biopsy any focal induration or ulceration.
• Cutaneous horn — a conical column of compact keratin overlying an AK, SCC, keratoacanthoma or verruca; the horn is a finding, not a diagnosis, and the base must be biopsied.
• Lichenoid AK — uncommon; a violaceous plaque resembling lichen planus, with a lichenoid infiltrate on histology. [1]

Atypical hosts: patients with darker skin show less erythema and more dyspigmentation or lichenification; immunosuppressed patients have more numerous, thicker, less inflamed lesions because immune surveillance is impaired.[1]

The mimics — and the discriminator that separates each

The discriminator line: rough, gritty scale on chronically sun-exposed skin is AK — and a trial of topical steroid or antifungal is the wrong move when malignancy is in the differential, because a transient partial response can delay the diagnosis of SCC in situ or invasive SCC. Biopsy when uncertain.[1]

Dermoscopy — the strawberry and its warning signs

Dermoscopy lifts diagnostic accuracy and separates AK from seborrhoeic keratosis, Bowen's disease and BCC. The classic pattern of facial, non-pigmented AK is the strawberry pattern — described by Zalaudek and colleagues:[7]

• Erythematous pseudonetwork — a red background from unfocused vessels coursing between follicular openings.
• White-yellow scale — overlying keratotic scale, fine or coarse.
• White circles — halo-like white rings around follicular openings (follicular plugs with perifollicular fibrosis). [1]

The dermoscopic red flags for progression are the signs that move you to biopsy: polymorphous vessels (a mixture of dotted, linear-irregular and hairpin), targetoid follicles or white-yellow opaque areas, erosion or ulceration without trauma, and — in pigmented lesions — a blue-white veil or polymorphous vessels that raise melanoma or pigmented SCC. Polymorphous vessels or erosion in a previously stable AK is a strong signal the lesion has become SCC in situ or invasive SCC.[1]

The bedside round and the biopsy rule

The assessment is clinical and dermoscopic; its jobs are to confirm the diagnosis, gauge the extent of field damage, and find any lesion suspicious for invasion.[1]

Focused history: cumulative sun exposure, outdoor occupation, sunburn history, phototype; previous skin cancers or AKs; immunosuppression, transplant status, prior PUVA or radiation; and — crucially — change in any specific lesion (thickening, growth, pain, bleeding, ulceration).[1]

Focused examination: inspect all sun-exposed sites (scalp, face, ears, neck, dorsal hands, forearms, lower lip); palpate for the gritty scale that is more obvious to touch than sight; assess the background field of elastosis, telangiectases and dyspigmentation; and look hard for the red flags of malignancy — induration, nodularity, ulceration, rapid change.[1]

Biopsy is mandatory when malignancy is suspected or the diagnosis is uncertain. Biopsy any AK that shows:[3][9]

• Thickening or induration, pain or tenderness, rapid growth
• Ulceration or bleeding, treatment failure after an adequate course, recurrence after apparent clearance
• A cutaneous horn at the base, to define the underlying pathology [1]

A shave, punch or incisional biopsy should sample the most suspicious area, including enough dermis to assess for invasion. The histological hallmark is dysplastic keratinocytes confined to the lower epidermis against a background of solar elastosis, with parakeratosis, basal-layer disorganisation with budding, and a chronic dermal infiltrate.[6]

Management — pick the right tool for the lesion or the field

AK management is stratified by lesion number, thickness, location and host — especially immunosuppression. There is no "one size fits all"; the choice is lesion-directed destruction versus field-directed therapy.[9][10]

Lesion-directed therapy — for a few discrete, thin lesions

For a few discrete, thin AKs, destructive or excisional treatments are quick, lesion-specific and provide histology when needed.[1]

• Cryotherapy (liquid nitrogen) is the gold-standard lesion-directed therapy for isolated thin AKs — freeze the lesion and a 1–2 mm rim of normal skin for about 5–10 seconds with a complete thaw before a second freeze-thaw cycle if used. Clearance approaches 98 percent for thin lesions after one cycle but falls with thickness. The cosmetic cost is hypopigmentation, worse in Fitzpatrick IV–VI and after aggressive cycles — biopsy first if invasive SCC is suspected.
• Curettage with electrocautery suits thicker or hypertrophic AKs and provides tissue for histology; it may leave a hypopigmented or atrophic scar, so use it cautiously on cosmetically sensitive sites.
• Surgical excision is reserved for lesions suspicious for invasive SCC or biopsy-proven SCC — not for straightforward thin AK. [1]

Field-directed therapy — for multiple lesions or field cancerization

When lesions are multiple, confluent or sit on a field of cancerization, the target is the entire sun-damaged field — to clear both visible AKs and the subclinical clones that would surface next. The agents, with their doses and the inflammation to expect:[1][2]

The 2021 AAD guidelines give strong recommendations to cryosurgery, 5-FU and imiquimod, and conditional recommendations to PDT and diclofenac as monotherapy or in combination. No single therapy is universally superior — individualise by lesion burden and thickness, field involvement, adherence, comorbidity and cosmesis.[1]

Practical pointers. 5-FU is highly effective but needs patient buy-in — pre-treatment counselling that erythema, erosion and crusting are expected and signal drug activity. Imiquimod suits patients who want a shorter intensive course or cannot tolerate 5-FU; the 2-week-on, 2-week-off regimen aids adherence. PDT is ideal for large fields, unreliable cream appliers, or those who want fewer visits, and gives excellent cosmesis.[5] Diclofenac is the gentlest but least potent. Combination therapy — cryotherapy of thicker lesions followed by field 5-FU or imiquimod, PDT followed by topical maintenance, or sequential field therapy — improves clearance in high-burden or refractory disease.[1]

Specific scenarios — the lip, the horn, the transplant patient

Actinic cheilitis is managed more aggressively than cutaneous AK because of its higher malignant potential: topical 5-FU or imiquimod for diffuse disease, PDT for extensive disease, vermilionectomy or laser ablation for severe, refractory or suspicious cases — and biopsy of any focal thickening, induration or ulceration.[1]

A cutaneous horn overlying an AK is a morphological finding, not a diagnosis; biopsy the base to exclude invasive SCC or keratoacanthoma.[1]

Solid-organ transplant recipients carry a dramatically higher AK burden and a much higher rate of progression to invasive SCC. The principles: aggressive field-directed therapy and regular surveillance; lesion-directed destruction of all visible AKs; consideration of mTOR inhibitor conversion (sirolimus) where feasible; and the vital negative result — nicotinamide did not work in transplant recipients in the ONTRANS trial, so do not rely on it in this group.[11]

Complications and pitfalls — where AK care goes wrong

The risk per lesion is low, but the risk per patient is real, because patients have many lesions and extensive field damage. Modern estimates put the annual per-lesion risk of progression to invasive SCC at roughly 0.025 to 0.075 percent — small for one lesion, significant across a field, and higher with immunosuppression.[1]

The greater danger is the lesion that has already become invasive SCC being treated as a benign AK with cryotherapy or topical 5-FU. This is why biopsy of any thickened, indurated or treatment-failing lesion is non-negotiable.[1]

The recurring pitfalls every candidate must name:[1]

• Undertreating thick lesions with cryotherapy — a single 5-second freeze is inadequate for a hyperkeratotic plaque and leaves residual atypia; curettage or biopsy it instead.
• Overtreating a single lesion with field therapy — a single thin AK needs cryotherapy, not a 4-week 5-FU course.
• Ignoring hypopigmentation risk in darker skin, where cryotherapy's cosmetic impact can exceed the disease.
• Failing to treat the field — treating only visible AKs leaves subclinical clones behind, and new lesions appear within months.
• Neglecting prevention — even the best destruction is undone by continued unprotected sun exposure. [1]

Prevention and surveillance — sun, nicotinamide, and the high-risk clinic

Primary prevention cuts cumulative UV; secondary prevention finds early lesions and stops progression. Photoprotection is the cornerstone: broad-spectrum SPF 30-plus sunscreen applied generously and reapplied every 2 hours; wide-brimmed hats, long sleeves, sunglasses and shade from 10 am to 4 pm; avoidance of tanning beds; and vitamin D through diet or supplements, not sun, in high-risk individuals. Sunscreen reduces new AKs and may allow partial regression of existing ones.[1]

Chemoprevention — know the two trials. Oral nicotinamide (vitamin B3) 500 mg twice daily reduced the incidence of new AKs and NMSC in the ONTRAC trial of high-risk immunocompetent patients — safe, cheap, well tolerated, offered to patients with frequent new AKs, prior NMSC or extensive field damage, but never a substitute for sun protection or surveillance.[4] In transplant recipients, the ONTRANS trial showed no significant benefit, so nicotinamide is not recommended there.[11]

Surveillance is risk-stratified:[1]

Teach self-examination for new or changing lesions, the warning signs of progression (thickening, induration, bleeding, ulceration), and the threshold for early review.[1]

Special populations and prognosis

Elderly and frail patients have the highest prevalence; balance efficacy against frailty, wound-healing and polypharmacy — field therapy may suit limited mobility better than repeated cryotherapy visits, and observation with sun protection is reasonable for the very frail with asymptomatic, non-suspicious lesions, though any red flag still triggers biopsy. In pregnancy, cryotherapy is the safe choice (locally destructive, minimal absorption); 5-FU and imiquimod are usually avoided and PDT deferred for lack of safety data. CLL accelerates both AK development and malignant transformation — proactive checks and early biopsy.[1]

Most AKs remain stable for long periods and a proportion regress spontaneously — but their presence marks a patient with enough UV damage to be at raised risk of further AKs and invasive SCC. The natural history is dynamic: individual lesions regress, persist or progress, and new lesions keep arising from the field. After treatment, disposition follows the risk stratification above.[1]

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The mantra

The mantra: easier felt than seen — treat the field, and biopsy any lesion that thickens, ulcerates or fails therapy.[1]

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Ward-round test — three stems, thirty seconds each

Stem 1 — the sandpaper scalp (answer)

A 72-year-old man has a bald scalp that feels like sandpaper, with scattered gritty pink macules across weathered skin. What is the diagnosis, what concept drives management, and what is the first-line treatment? Model: This is field cancerization with multiple actinic keratoses — the gritty, scaly macules that are easier felt than seen on sun-damaged skin. The driving concept is the field: the visible AKs are the tip of an iceberg of subclinical premalignant clones, so treating only the spots fails. Because the lesions are multiple and confluent, the first-line treatment is field-directed therapy — topical 5-FU, imiquimod or photodynamic therapy — not spot cryotherapy.[1]

Stem 2 — the thickened lesion on the crown (answer)

Among that patient's gritty macules, one on the crown has thickened over two months and is now tender. What must you do, and why? Model: Biopsy it. Thickening, induration, pain, rapid growth, ulceration or treatment failure are the red flags that an AK has crossed the basement membrane into invasive SCC, and the classic error is to freeze or topical-treat a lesion that has already transformed. Biopsy the most suspicious area with enough dermis to assess invasion, then manage by stage. Never destroy a lesion blind when invasion is suspected.[1]

Stem 3 — the transplant recipient with rapidly changing AKs (answer)

A renal transplant recipient, eight years out, has dozens of AKs and three new thickening lesions in six months. What two levers change his immunosuppression, and what chemoprevention does NOT work in this group? Model: In the transplant recipient, AK burden and malignant transformation are far higher. Two levers: reduce the overall immunosuppressive load where graft function allows, and consider conversion to an mTOR inhibitor (sirolimus), which can reduce NMSC burden. The chemoprevention that does NOT work here is nicotinamide — the ONTRANS trial showed no significant benefit in transplant recipients, so do not rely on it. Biopsy the three thickening lesions, institute aggressive field therapy, and surveil every 3–6 months.[11]

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References

1. [1]Willenbrink TJ, Ruiz ES, Cornejo CM, et al. Field cancerization: Definition, epidemiology, risk factors, and outcomes J Am Acad Dermatol, 2020.PMID 32387665
2. [2]Dianzani C, Conforti C, Giuffrida R, et al. Current therapies for actinic keratosis Int J Dermatol, 2020.PMID 32012240
3. [3]Worley B, Harikumar V, Reynolds K, et al. Treatment of actinic keratosis: a systematic review Arch Dermatol Res, 2023.PMID 36454335
4. [4]Chen AC, Martin AJ, Choy B, et al. A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention N Engl J Med, 2015.PMID 26488693
5. [5]Wang JY, Zeitouni N, Austin E, et al. Photodynamic therapy: Clinical applications in dermatology J Am Acad Dermatol, 2026.PMID 39986392
6. [6]Ferrándiz C, Malvehy J, Guillén C, et al. Precancerous Skin Lesions Actas Dermosifiliogr, 2017.PMID 27658688
7. [7]Zalaudek I, Giacomel J, Argenziano G, et al. Dermoscopy of facial nonpigmented actinic keratosis Br J Dermatol, 2006.PMID 17034524
8. [8]Benjamin CL, Ananthaswamy HN p53 and the pathogenesis of skin cancer Toxicol Appl Pharmacol, 2007.PMID 17270229
9. [9]Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis: Executive summary J Am Acad Dermatol, 2021.PMID 34111497
10. [10]Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis J Am Acad Dermatol, 2021.PMID 33820677
11. [11]Allen NC, Martin AJ, Snaidr VA, et al. Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients N Engl J Med, 2023.PMID 36856616