Skin CancerCore · 8 min read

Actinic Keratosis (AK)

UV-driven intraepidermal dysplasia on the in-situ end of the keratinocyte cancer spectrum, recognized dermoscopically by the strawberry pattern, white circles, and rosettes.

By Dr. Yehonatan KaplanPublished Updated

In brief

Actinic keratosis is the most common cutaneous precancer and represents the earliest histologically detectable step in the field-cancerized spectrum that can progress to invasive squamous cell carcinoma. AK and SCC share UV-driven TP53 mutations and are now widely viewed as different stages of one neoplastic continuum rather than separate diseases. Dermoscopic recognition matters because management is field-directed and topical for AK, but invasive SCC requires surgery. The dermoscopic features track histopathology closely: surface scale and a red pseudonetwork around plugged follicles correspond to parakeratosis and dilated papillary vessels, while white circles around follicles indicate acanthosis with hypergranulosis at the infundibulum. Pigmented AK on the face is the great mimic of lentigo maligna and demands a structured comparative approach.

Clinical content

01AK is the in-situ phase of an evolving keratinocyte neoplasm. The estimated annual progression of an individual AK to invasive SCC is low (under 1 percent per lesion per year in most cohorts) but the cumulative risk in a patient with extensive field damage is meaningful, and there is no reliable way to predict which lesion will progress. Treat all AKs at first development.

02Macular non-pigmented AK on the face (Olsen Grade I) shows the classic strawberry pattern: a red pseudonetwork formed by dilated vessels in dermal papillae interrupted by yellow-white keratin-plugged follicular openings, often surrounded by a fine white halo (targetoid follicles). Background erythema rather than a discrete vascular pattern dominates. Surface scale is fine and patchy.

03Hypertrophic AK (Olsen Grade II to III) develops thicker scale that obscures the underlying vessels and the strawberry pattern. White structureless areas, follicular hyperkeratosis with prominent plugs, and a wool-like white-yellow surface keratin become visible. Once a hypertrophic AK becomes indurated, induced bleeding appears, or vessels become visible through the keratin (dotted, glomerular, hairpin), think transition to invasive SCC and biopsy.

04Pigmented AK is the most important mimic of facial lentigo maligna. Features that argue for pigmented AK are: an underlying strawberry pattern, surface scale, an inner gray halo around follicular openings (corresponding to perifollicular pigment incontinence), and intact, evenly distributed follicular ostia. Features favoring lentigo maligna are rhomboidal pigment around follicles, asymmetric pigmented follicular openings, obliterated follicular ostia, and gray dots and granules in non-follicular distribution.

05Rosettes are four-point white star structures only visible under polarized dermoscopy. They correspond to follicular hyperkeratosis and parakeratotic plugs and are common in AK on chronically photodamaged skin. They are not specific for AK (also seen in SCC, BCC, scars) and should not by themselves drive a malignancy diagnosis, but their presence supports actinic damage.

06Field cancerization is the concept that the entire chronically UV-exposed area is genetically primed. Treating one visible AK while leaving the field untreated leaves a high recurrence rate. Field-directed therapy (5-FU plus calcipotriol, imiquimod, photodynamic therapy, tirbanibulin) targets clinical and subclinical lesions across the cosmetic unit. The Jansen randomized trial (NEJM 2019) found 5-FU achieved the highest 12-month sustained reduction (74.7 percent free of disease progression) compared with imiquimod (53.9), MAL-PDT (37.7), or ingenol mebutate (28.9).

07The treatment ladder is anchored by lesion count, distribution, comorbidity, and patient tolerance. Single discrete AK on the face: cryotherapy or curettage. Field disease, multiple AKs: topical 5-FU 5 percent (with calcipotriol for the longest documented prophylactic benefit), imiquimod, tirbanibulin (5-day regimen), or PDT. 5-FU wraps work for extensive limb AK in mobile patients. Hypertrophic limb AK responds to combination cryotherapy followed by 5-FU. For organ transplant recipients with sustained AK burden, consider acitretin or capecitabine and dose reduction or mTOR-inhibitor switch.

08Olsen grading (clinical grades I, II, III) does not predict progression risk well; biopsy threshold should be triggered by induration, bleeding, persistence beyond a treatment cycle, rapid growth, neurologic symptoms (pain, paresthesia), or any of the dermoscopic invasive-conversion features. The 2018 PRO histologic classification (PRO I, II, III, based on basal proliferation pattern) better predicts which AKs harbor the histologic features that correlate with progression.

Key dermoscopic features

Red pseudonetwork (strawberry pattern)
Pathognomonic for non-pigmented facial AK. Dilated vessels in dermal papillae visible between yellow-plugged follicular openings.Background erythema with regular fine vessels around prominent perifollicular yellow-white plugs.
Targetoid follicles (white halos around plugged follicles)
Acanthosis with hypergranulosis at the follicular infundibulum. A field marker of facial photodamage.Yellow-white keratotic plug at center, fine white perifollicular ring, surrounding red pseudonetwork.
Surface scale
Parakeratosis. Present in over 90 percent of AKs in published series.White or yellow superficial scale, diffuse or patchy distribution.
Rosettes (under polarized light)
Follicular hyperkeratosis with parakeratosis. Supports actinic damage but not specific.Four-point white star structures inside follicular openings, only visible with polarization.
Inner gray halo
Pigment incontinence in macrophages around the follicular infundibulum. Helpful in distinguishing pigmented AK from lentigo maligna.Thin gray rim immediately surrounding follicular ostium, on a background that may have brown structureless areas or fine pigmented network.
Hyperkeratotic follicles
Olsen grade II-III. Plugs become opaque yellow-white and thick.Coarse central keratin filling enlarged follicular openings, with surface white-yellow scale obscuring the pseudonetwork.
White structureless areas
In hypertrophic AK, signals dermal fibrosis or thick orthokeratosis; in early SCC arising in AK, more prominent and central.Featureless white zones; if focal and asymmetric within an AK, raises concern for early invasion.
Background erythema (negative SCC predictor)
Diffuse erythema as the dominant feature without focal vascular structures supports AK over early SCC. In the Papageorgiou 2022 multivariate analysis, background erythema was a negative predictor of early SCC (OR 0.22).Soft pink-red wash without discrete dotted, glomerular, or hairpin vessels.
Pigmented variant features
Brown structureless areas, slate-gray dots in linear arrangement around follicles, fine annular-granular pattern. Distinguishing from lentigo maligna is the practical challenge.Thin pigmented network on photodamaged skin, with intact follicular openings; underlying strawberry pattern, inner gray halo, and surface scale favor pigmented AK.

High yield clinical points15 pearls in 5 groups

Recognition & pattern analysis

6 points
1
Strawberry pattern is the dermoscopic signature of facial macular AK. Red pseudonetwork interrupted by yellow-plugged follicles surrounded by fine white halos. The combination of these three findings on chronically sun-exposed facial skin is highly specific for AK.
2
White circles around follicles signal invasion. Originally called targetoid hair follicles by Zalaudek (JAAD 2012), now widely termed white circles. Histologically they correspond to acanthosis and hypergranulosis around follicles. They are more frequent and prominent in invasive SCC than in AK and were listed by Rosendahl (2012) as the most useful single feature distinguishing invasive SCC from in-situ disease.
3
Pigmented AK on the face: look for the strawberry pattern under the pigment. If you see the underlying red pseudonetwork plus yellow follicular plugs and surface scale, the diagnosis is pigmented AK and lentigo maligna becomes much less likely. Inner gray halos around follicles also favor pigmented AK.
4
Rosettes are not pathognomonic for AK. They occur in any condition with follicular hyperkeratosis (SCC, BCC, scars, discoid lupus). Their presence supports actinic damage but should not drive a specific diagnosis.
5
Daily sunscreen use prevents new AKs and SCCs. Green et al (J Clin Oncol 2011) showed regular sunscreen reduced both AK incidence and subsequent SCC. Combine with hat, clothing, and avoidance of tanning beds.
6
Oral nicotinamide 500 mg twice daily reduces AK and NMSC in high-risk patients. ONTRAC trial (Chen NEJM 2015) demonstrated a 13 percent reduction in new AKs and 23 percent reduction in NMSC over 12 months. Effect disappears after stopping. Safe in CKD; not the same as nicotinic acid.

Management & treatment

4 points
1
Treat the field, not just the lesion. Field-directed therapy targets subclinical AKs across the cosmetic unit. Topical 5-FU 5 percent plus calcipotriol (Cunningham 2017, Jansen 2019, Rosenberg 2019) provides the longest documented chemoprevention against subsequent SCC.
2
5-FU plus calcipotriol delivered the strongest SCC prevention signal. In the follow-up of Cunningham et al, only 7 percent of patients receiving 4-day topical 5-FU plus calcipotriol developed SCC on the treated face/scalp within 3 years versus 28 percent in the petroleum-jelly plus 5-FU control (HR 0.215, p=0.032).
3
Hypertrophic AK obscures dermoscopic clues until the keratin is removed. If thick scale prevents evaluation, gentle curettage of the surface keratin under topical anesthesia, followed by repeat dermoscopy, often reveals the underlying vascular and structural pattern and helps decide between AK and invasive SCC.
4
Document field response by photography. AK field treatment response is best assessed by comparison photographs at baseline and 1-3 months post-cycle, not by counting individual lesions, because new ones appear and others involute.

Pitfalls & mimics

3 points
1
Lentigo maligna mimics pigmented AK by obliterating follicles. Rhomboidal structures around follicles, asymmetric pigmented follicular openings, gray dots in non-follicular distribution, and obliteration of follicular ostia all favor LM. When in doubt, biopsy or use reflectance confocal microscopy to map the lesion.
2
Olsen Grade III AK has the highest pretest probability of harboring invasive disease. When you have clinically thick AK with crust or erosion, biopsy first; do not treat empirically with topicals.
3
Topical retinoids do not prevent AK or SCC. VATTC trial showed topical tretinoin did not reduce keratinocyte carcinoma incidence (Weinstock J Invest Dermatol 2012). Reserve oral acitretin or isotretinoin for organ transplant recipients with high SCC burden, where it does reduce SCC, accepting that benefits disappear after discontinuation.

When to biopsy

1 point
1
Induration on palpation is the simplest invasion alarm. AKs are flat or minimally elevated. Any indurated, infiltrative, or tender lesion arising in actinic skin should be treated as SCC until proven otherwise on biopsy with deep reticular dermis included.

Recent changes (2022 onward)

1 point
OR 3.83
Background erythema favors AK; focal dotted/glomerular/hairpin vessels favor early SCC. In the Papageorgiou 2022 prospective study comparing AK and early SCC, background erythema had an OR of 0.22 for SCC. When you see well-formed dotted (OR 3.83), hairpin (OR 12.12), or branched linear vessels and white structureless areas (OR 3.58), invasion is much more likely.

Lectures covering this topic10 lectures

AAD 2026U003 · #01
Cases Where Confocal Saved the Day
Harold Rabinovitz, MD
AAD 2026U004 · #01
Real-Time Identification and Management of Actinic Keratoses
Drew A. Emge, MD, MSc
Excellence (main)DE-MAIN · #03
Basal Cell Carcinoma and Squamous Cell Carcinoma
G. Argenziano and A. Lallas
Excellence Intl 2025DE-INTL · #10
Dermoscopy of NMSC, Update
Aimilios Lallas
Excellence PracticalDE-PRACT · #02
Facial Cases
Giuseppe Argenziano and Aimilios Lallas
Excellence PracticalDE-PRACT · #05
Difficult Differentials of BCC and SCC
Giuseppe Argenziano and Aimilios Lallas
Academy 2025ACAD25 · #06
What We Have Learned in the Last Few Years About NMSC
Aimilios Lallas
ADM 2025ANNUAL13 · #01
Actinic Keratosis and Squamous Cell Carcinoma
Harold Rabinovitz, MD
ADM 2025ANNUAL13 · #02
Approach to Evaluating Facial Lesions
Harold Rabinovitz, MD
ADM 2025ANNUAL13 · #19
Management of BCC and AK-SCC: The In-Between
George Martin, MD

Notable updates & conceptual milestones7 updates

PRO histologic classification (PRO I-III)

2018

Schmitz et al (JEADV 2018) proposed a basal proliferation pattern classification (PRO I crowding, PRO II budding, PRO III invasive proliferation reaching deeper than the upper one-third of the epidermis) that better correlates with progression risk than Olsen clinical grading.

Tirbanibulin 1% ointment 5-day regimen

2021

Phase III trials (Blauvelt NEJM 2021) showed 44-54 percent complete clearance vs 5-13 percent with vehicle for facial/scalp AK, with a much shorter course and milder reaction than 5-FU or imiquimod.

5-FU plus calcipotriol immunotherapy

2017-2019

Cunningham (J Clin Invest 2017) showed adding calcipotriol to topical 5-FU induced TSLP-mediated TH2 immunity in AK lesions and produced near-complete clearance after 4 days. Long-term follow-up (Rosenberg JCI Insight 2019) showed sustained protection against subsequent SCC.

UV-fluorescence dermoscopy for field mapping

2022-2025

Built-in 365 nm LEDs in modern dermatoscopes allow visualization of subclinical AK and field damage as darkened areas of altered autofluorescence, useful for biopsy site selection and treatment monitoring without darkening the room.

Line-field confocal OCT (LC-OCT) for AK grading

2024-2025

LC-OCT combines micron-scale resolution with depth penetration to ~500 microns, allowing non-invasive distinction between AK Olsen grades and detection of early dermal invasion in real time. Published meta-analyses suggest sensitivity above 90 percent for SCC detection.

Tirbanibulin 1% real-world data (TIRBASKIN)

2026

Tirbanibulin 1% ointment (5 consecutive daily applications to a 25 cm2 face or scalp area) produces complete clearance in 54% and partial clearance in 76% of patients at day 57 in routine practice. Erythema and flaking are usually mild and resolve within 2 months.

Chemoprevention evidence consolidated

2026

2026 systematic review of 11 RCTs in immunocompetent adults: daily sunscreen cuts AK incidence 24-51% and SCC risk 39%; nicotinamide 500 mg twice daily cuts SCCs 30% and AKs 13-35%; a single 4-day course of topical 5-FU cuts superficial BCC incidence by 59%. Retinoids and DFMO are not recommended.

Bottom line

UV-driven intraepidermal dysplasia on the in-situ end of the keratinocyte cancer spectrum, recognized dermoscopically by the strawberry pattern, white circles, and rosettes.

15 clinical points · 7 recent updates · 15 references

Source content

AAD 2026 · U004 · #01

Real-Time Identification and Management of Actinic Keratoses

Drew A. Emge, MD, MSc · University of Kansas Medical Center, Kansas City, Kansas

References

Sources cited in the lecture content or that underpin the clinical points above. Verify with primary sources before practice changes.

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