Actinic Keratosis

Updated: Jul 14, 2017
  • Author: James M Spencer, MD; Chief Editor: William D James, MD  more...
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Overview

Practice Essentials

Actinic keratosis (AK) is a UV light–induced lesion of the skin that may progress to invasive squamous cell carcinoma. It is by far the most common lesion with malignant potential to arise on the skin. See the image below.

Actinic keratosis. Courtesy of Hon Pak, MD. Actinic keratosis. Courtesy of Hon Pak, MD.

See Nonmelanoma Skin Cancers You Need to Know and Can You Recognize Benign Skin Lesions From Cancerous Ones?, Critical Images slideshows, to help correctly identify various lesions.

Signs and symptoms

Actinic keratoses develop as follows:

  • The lesions begin as small, rough spots that are easier felt than seen and that have what is often described as a sandpaperlike texture [1]
  • With time, the lesions enlarge, usually becoming red and scaly
  • Most lesions are only 3-10 mm, but they may enlarge to several centimeters in size [1, 2, 3]

The typical patient with actinic keratoses is an elderly, fair-skinned, sun-sensitive person. [4] The lesions arise in areas of long-term sun exposure, including the face, ears, and, in men, bald scalp, as well as in the dorsal forearms and hands. [5, 6]

Patients may develop multiple lesions within a single anatomic area, to the extent that the lesions collide and produce confluent actinic keratosis over a relatively large area. The following variants can occur [7] :

  • Brown (pigmented actinic keratosis)
  • Atrophic
  • Bowenoid
  • Lichen planus–like
  • Exaggerated hyperkeratosis - Produces a hornlike projection, known as a cutaneous horn, above the skin surface

The image below is a typical depiction of actinic keratosis.

Erythematous, scaly lesions on the temple area, ty Erythematous, scaly lesions on the temple area, typical of actinic keratosis.

See Clinical Presentation for more detail.

Diagnosis

Histology

A skin biopsy is indicated to confirm the diagnosis and to rule out invasive squamous cell carcinoma for suspicious or more advanced lesions (ie, those with more pronounced hyperkeratosis, increased erythema, or induration or nodularity). [8, 9] A biopsy is also indicated for recurrent lesions or those that are unresponsive to therapy.

Actinic keratosis is characterized by dysplasia and architectural disorder of the epidermis, as follows [1] :

  • Abnormal keratinocytes of the basal layer that are variable in size and shape
  • Altered cellular polarity
  • Nuclear atypia
  • Hyperkeratosis and parakeratosis of the epidermis
  • Irregular acanthosis may be present

In general, hair follicles, sebaceous glands, and apocrine and eccrine ducts are not involved. [1]

Fluorescence

Fluorescence with the use of a photosensitizing drug (methyl ester of 5-aminolevulinic acid [ALA], a precursor of protoporphyrin) commonly used during photodynamic therapy (PDT) has been described as a diagnostic tool for actinic keratosis. [10] Areas of involvement, including occult areas of abnormal skin, emit a pink fluorescence with a Wood lamp or photodynamic therapy lamp. [10]

See Workup for more detail.

Management

Treatment consists of the following categories:

  • Medical therapy - including pharmacologic treatment and PDT
  • Surgical destruction of the lesion
  • Pharmacologic treatment

Medications approved by the US Food and Drug Administration (FDA) for the treatment of actinic keratosis include the following [11, 12, 13] :

  • Topical 5-fluorouracil (5-FU)
  • Imiquimod cream
  • Ingenol mebutate gel
  • Topical diclofenac gel

Photodynamic therapy

PDT uses a light-sensitizing compound that preferentially accumulates in actinic keratosis cells, where it can be activated by the appropriate wavelength of light. Delta-aminolevulinic acid is a component of the heme biosynthetic pathway that accumulates preferentially in dysplastic cells. Once inside these cells, it is enzymatically converted to protoporphyrin IX, a potent photosensitizer. With exposure to light of an appropriate wavelength, oxygen free radicals are generated and cell death results. [14]

Surgery

Types of surgery used in the eradication of actinic keratoses include the following [15, 16, 17] :

  • Cryosurgery
  • Curettage, shave excision, and conventional excision - For lesions suggestive of invasive cancer
  • Cosmetic resurfacing procedures - Including medium and deep chemical peels, dermabrasion, and ablative laser resurfacing

See Treatment and Medication for more detail.

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Background

Actinic keratosis (AK) is a UV light–induced lesion of the skin that may progress to invasive squamous cell carcinoma. [18, 19, 20] It is by far the most common lesion with malignant potential to arise on the skin. Actinic keratosis is seen in fair-skinned persons on skin areas that have had long-term sun exposure. [5] In Australia, the country with the highest skin cancer rate in the world, the prevalence of actinic keratosis among adults older than 40 years has been reported to range from 40-60%. [21]

The premalignant nature of actinic keratosis was recognized almost 100 years ago, and the name literally means thickened scaly growth (keratosis) caused by sunlight (actinic). In the United States, actinic keratosis represents the second most frequent reason for patients to visit a dermatologist. [22]

An actinic keratosis may follow 1 of 3 paths; it may regress, it may persist unchanged, or it may progress to invasive squamous cell carcinoma. The actual percentage that progress to invasive squamous cell carcinoma remains unknown, and estimates have varied from as low as 0.1% to as high as 10%. [18, 23]

In 2009, Criscione and colleagues conducted a study examining the progression of actinic keratoses to squamous cell carcinoma and basal cell carcinoma. [24] The study examined 7784 actinic keratoses in a high-risk population and found that nearly 65% of primary squamous cell carcinomas and 36% of primary basal cell carcinomas arise from clinically diagnosed actinic keratoses. Furthermore, risk of progression of actinic keratosis to squamous cell carcinoma was 0.60% at 1 year and 2.57% at 4 years, which is 6-8 times more frequent than has been reported in some prior studies.

Although it is impossible to predict which individual lesion will follow which course, as most patients have many lesions, accessing risk becomes more significant and aids in tailoring treatments. Overall, actinic keratoses can be safely and effectively eradicated, and, therefore, therapy is warranted.

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Pathophysiology

Actinic keratoses arise on fair-skinned people in areas of long-term sun exposure, such as the face, ears, bald scalp, forearms, and backs of the hands. [5] However, they may occur on any area that is repeatedly exposed to the sun, such as the back, the chest, and the legs. Long-term UV light exposure is implicated as the cause from both epidemiologic observations and molecular analysis of tumor cells. [19, 5] Actinic keratosis frequency correlates with cumulative UV exposure. [5] Therefore, the frequency of actinic keratosis increases with each decade of life, is greater in residents of sunny countries closer to the equator, and is greater in persons with outdoor occupations. [5, 4] DNA analysis of the cells within actinic keratoses shows characteristic UV-induced mutations in key genes, including TP53 and deletion of the gene coding for p16 tumor suppressor protein. [19, 25, 26]

Over time, actinic keratoses may develop into invasive squamous cell carcinoma; according to one study of almost 7000 patients, among the small percentage of actinic keratoses that progress into squamous cell carcinoma, the length of time for this transformation to occur was approximately 2 years. [27] Development of actinic keratoses may occur as early as the third or fourth decade of life in patients who live in areas of high solar radiation, are fair-skinned, and do not use sunscreen for photoprotection. [5] Usually, patients demonstrate a background of solar-damaged skin with telangiectasias, elastosis, and pigmented lentigines. [1]

In both histologic and molecular parameters, actinic keratoses share features with squamous cell carcinoma. [28] Actinic keratosis is an epidermal lesion characterized by aggregates of atypical, pleomorphic keratinocytes at the basal layer that may extend upwards to involve the granular and cornified layers. [28] The epidermis itself shows an abnormal architecture, with acanthosis, parakeratosis, and dyskeratosis. Cellular atypia is present, and the keratinocytes vary in size and shape; mitotic figures are present. [28] This presentation may resemble Bowen disease or carcinoma in situ, and the distinction between the two is a matter of degree (extent of the lesion) rather than differences in individual cells. [28]

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Frequency

United States

Actinic keratosis occurs primarily in whites, the frequency of which correlates with cumulative UV exposure. [5] Therefore, frequency increases with age, proximity to the equator, and outdoor occupation. Actinic keratoses are seen more in men than in women and have also been correlated with a high-fat diet. [4, 29] Overall, the rate in the United States is estimated to range from 11-26%. [21]

International

The prevalence is highest in Australia, where a light-skinned population is common and outdoor sports are very popular activities. [30] Overall, actinic keratosis is estimated to be present in 40-60% of the Australian population older than 40 years. [21]

Race

The prevalence of actinic keratosis is much higher in individuals with fair skin and blue eyes and is lower in individuals with darker skin types. [4] Actinic keratosis is relatively nonexistent in black skin. [31] Patients with actinic keratoses tend to have Fitzpatrick type I or II skin, which burns and does not tan. [5] The prevalence is reduced precipitously in persons with Fitzpatrick types III, IV, and V skin and is nonexistent in those with Fitzpatrick type VI skin. [31] Although the incidence of cutaneous malignancies in darker-skinned individuals is much lower than in white persons, UV exposure may still play a role in the etiology of squamous and basal cell carcinoma; screening and sun safety education should still be promoted because cutaneous malignancies in darker-skinned individuals can be very aggressive. [31]

Sex

The prevalence of actinic keratosis is higher in men than in women. [5] This is theorized to result from a greater likelihood that men have an outdoor occupation and thus have greater cumulative UV exposure. [4]

Age

One of the most important determinants of actinic keratosis risk is age, particularly when evaluated with other strong predictors, including cumulative sun exposure, place of birth, occupation, and skin type. [5, 4] Actinic keratoses can occur in patients aged 20-30 years, but they are more common in patients aged 50 years and older. [5]

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Mortality/Morbidity

Lesions begin as barely perceivable rough spots of skin, better felt than seen. [1, 10] Early lesions feel like sandpaper; later lesions become erythematous, scaly plaques that may enlarge to several centimeters. [5, 1] Lesions may remain unchanged for years, may spontaneously regress, or may progress to invasive squamous cell carcinoma. [23] Most actinic keratoses do not progress to invasive squamous cell carcinoma; however, most invasive squamous cell carcinomas have evidence of a preexisting actinic keratosis. [5, 23] Invasive squamous cell carcinoma may produce significant morbidity by direct extension into facial structures. In less than 10% of cases, invasive squamous cell carcinoma may metastasize, with a low 5-year survival rate. [32, 33]

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Prognosis

The prognosis for actinic keratosis is good. With continuing surveillance and treatment, these lesions can be managed individually. The opportunity for them to develop into invasive squamous cell carcinomas can be prevented by aggressive therapy and sun protection. However, the prognosis in a person with long-term exposure is more guarded because of the multitude of their lesions. Some lesions may progress and develop into invasive squamous cell carcinomas. [18, 23] Patients with extensive involvement unresponsive to cryosurgery and topical therapy may benefit from skin resurfacing by dermabrasion, [17] chemical peeling, or laser resurfacing. [16]

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Patient Education

Encourage patients to wear sunscreens, to limit sun exposure, and to adjust their hobby or profession to decrease sun exposure. For patient education resources, see the Skin Conditions & Beauty Center. Additionally, see the patient education article Skin Cancer.

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