eMedicine Specialties > Dermatology > Malignant Neoplasms

Actinic Keratosis

James M Spencer, MD, Professor of Clinical Dermatology, Mount Sinai School of Medicine, New York; Private Practice, Spencer Dermatology, St Petersburg, Florida
Amy Lynn Basile, DO, MPH, Sun Coast Hospital/Largo Medical Center, Largo, Florida

Updated: Feb 18, 2009

Introduction

Background

Actinic keratosis (AK) is a UV light–induced lesion of the skin that may progress to invasive squamous cell carcinoma.^1,2,3 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.⁴ 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%.⁵

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.⁶

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%.^1,7 Furthermore, predicting which course each individual lesion will follow is impossible.

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.⁴ 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.^2,4 Actinic keratosis frequency correlates with cumulative UV exposure.⁴ 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.^4,9 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.^2,10,11

Clinically, actinic keratoses range from barely perceptible rough spots of skin to elevated, hyperkeratotic plaques several centimeters in diameter.¹² Most often, they appear as multiple discrete, flat or elevated, keratotic lesions. Lesions typically have an erythematous base covered by scale (hyperkeratosis).¹² They are usually 3-10 mm in diameter and gradually enlarge into broader, more elevated lesions.

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.¹³ 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.⁴ Usually, patients demonstrate a background of solar-damaged skin with telangiectasias, elastosis, and pigmented lentigines.¹⁴

In both histologic and molecular parameters, actinic keratoses share features with squamous cell carcinoma.¹⁵ 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.¹⁵ 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.¹⁵ This presentation may resemble Bowen disease or carcinoma in situ, and the distinction between the 2 is a matter of degree (extent of the lesion) rather than differences in individual cells.¹⁵

Often, marked hyperkeratosis and areas of parakeratosis with loss of the granular layer are present. A dense inflammatory infiltrate is usually present. The case has been made that actinic keratosis is the earliest manifestation of squamous cell carcinoma and should be regarded as such rather than as a precancerous lesion.^15,16 Others have argued that calling actinic keratosis a carcinoma unduly alarms patients. Cockerell has proposed renaming the lesion keratinocytic intraepidermal neoplasia, using a nomenclature analogous to cervical and vulvar intraepithelial neoplasia.¹⁵

Frequency

United States

Actinic keratosis occurs primarily in whites, the frequency of which correlates with cumulative UV exposure.⁴ 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.^9,17 Overall, the rate in the United States is estimated to range from 11-26%.⁵

International

The prevalence is highest in Australia, where a light-skinned population is common and outdoor sports are very popular activities.¹⁸ Overall, actinic keratosis is estimated to be present in 40-60% of the Australian population older than 40 years.⁵

Mortality/Morbidity

Lesions begin as barely perceivable rough spots of skin, better felt than seen.^14,19 Early lesions feel like sandpaper; later lesions become erythematous, scaly plaques that may enlarge to several centimeters.^4,14 Lesions may remain unchanged for years, may spontaneously regress, or may progress to invasive squamous cell carcinoma.⁷ Most actinic keratoses do not progress to invasive squamous cell carcinoma; however, most invasive squamous cell carcinomas have evidence of a preexisting actinic keratosis.^4,7 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.^20,21

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.⁹ Actinic keratosis is relatively nonexistent in black skin.²² Patients with actinic keratoses tend to have Fitzpatrick type I or II skin, which burns and does not tan.⁴ 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.²² 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.²²

Sex

The prevalence of actinic keratosis is higher in men than in women.⁴ This is theorized to result from a greater likelihood that men have an outdoor occupation and thus have greater cumulative UV exposure.⁹

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.^4,9 Actinic keratoses can occur in patients aged 20-30 years, but they are more common in patients aged 50 years and older.⁴

Clinical

History

Actinic keratoses are seen almost exclusively in whites, especially those with skin phototypes I and II.⁹ The incidence increases with each decade of life, and men have a slightly increased frequency of actinic keratosis.^5,9 Actinic keratosis is correlated with long-term UV exposure, such as occurs in persons with outdoor occupations.⁹

Patient who are immunosuppressed following organ transplantation are at markedly increased risk of developing actinic keratoses.²³ The lesions still arise in areas of long-term exposure,^13,24,25 and they are thought to be actinically induced.

Physical

The typical patient with actinic keratoses is an elderly, fair-skinned, sun-sensitive person.⁹ The lesions arise in areas of long-term sun exposure, including the face, ears, bald scalp in men, and the dorsal forearms and hands.^4,24 Actinic keratoses begin as small rough spots that are easier felt than seen, often described as being similar to rubbing sandpaper.¹⁴ With time, the lesions enlarge, usually becoming red and scaly; most are only 3-10 mm, but they may enlarge to several centimeters.^14,26,27

Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

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

Causes

Actinic keratoses are induced by UV light. Both epidemiologic observations and molecular biologic characteristics of the tumor cells suggest UV light is sufficient by itself to induce actinic keratosis.^2,11 Sensitivity to UV light is inherited; actinic keratoses occur more frequently in fair, redheaded, or blonde patients who burn frequently and tan poorly.⁴ Increased sun exposure and higher-intensity exposure increase the chance of actinic keratosis development. Immunosuppression following organ transplantation dramatically increases the risk of developing actinic keratoses²³ ; however, actinic keratoses do not occur without sun exposure.

Additional studies have shown an association between cutaneous human papillomavirus and actinic keratosis.^29,30,31 The role of human papillomavirus in skin tumorigenesis was discovered the 1950s, and the group of known human papillomavirus types associated with skin tumorigenesis has been classified as beta-papillomavirus .³⁰ Beta-papillomavirus DNA has been identified in healthy skin and in squamous cell carcinoma, basal cell carcinoma, and actinic keratosis. A 2007 study suggests that only a small association exists between beta-papillomavirus and actinic keratosis; however, when evaluated in combination with other risk factors including age, sun damage, and skin color, the risk for actinic keratosis increased as much as 13-fold.³⁰ The exact mechanism by which this family of viruses contributes to tumor growth remains unknown.

Differential Diagnoses

Other Problems to Be Considered

• Discoid lupus erythematosus - Demonstrates dyspigmentation, dilated follicles, and atrophy
• Seborrheic keratosis - Greasy, brown crusts; sharply demarcated borders; nonerythematous base; may occur in nonexposed areas
• Bowen disease - A larger plaque with a sharp outline
• Invasive squamous cell and basal cell carcinomas - Indurated nodular lesions, more rapid growth, eroded or ulcerated surface^32,33

Workup

Laboratory Studies

• Blood work is not indicated.

Procedures

• 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, induration or nodularity).^32,33
• A biopsy is also indicated for recurrent lesions or those that are unresponsive to therapy.
• 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.¹⁹ Areas of involvement, including occult areas of abnormal skin, emit a pink fluorescence with a Wood lamp or photodynamic therapy lamp.¹⁹

Histologic Findings

Actinic keratosis is characterized by dysplasia and architectural disorder of the epidermis.¹⁴ Keratinocytes of the basal layer are abnormal and are variable in size and shape; cellular polarity is altered, and nuclear atypia is seen.¹⁴ These alterations may extend upward to the granular layer, which may be thinned. Overall, the epidermis exhibits hyperkeratosis and parakeratosis, and irregular acanthosis may be present.¹⁴ In general, hair follicles, sebaceous glands, and apocrine and eccrine ducts are not involved.¹⁴

Treatment

Medical Care

Actinic keratoses may remain unchanged, spontaneously resolve, or progress to invasive squamous cell carcinoma.¹⁴ The fate of any one actinic keratosis is impossible to predict. Although the risk of progression of any one actinic keratosis to invasive squamous cell carcinoma is small (at most approximately 10%),¹ a patient may have many lesions, and thus the risk of progression becomes significant. Additionally, actinic keratoses can be clinically indistinguishable from more serious cutaneous malignancies, including squamous cell carcinoma and lentigo maligna.^34,35 Therapy is generally well tolerated and simple; therefore, treatment of all actinic keratoses is warranted.

The appropriate treatment is generally chosen based on the number of lesions present and the efficacy of the treatment.³⁶ Additional variables to consider include persistence of the lesion(s), age of the patient, history of skin cancer, and tolerability of the treatment modality.¹ Treatment consists of 2 broad categories: surgical destruction of the lesion and medical therapy. Medical management begins with educating the patient to limit sun exposure. Patients should be cautioned to avoid sun exposure from 10:00 am to 3:00 pm as much as possible. They also must wear adequate sunscreens and protective clothing daily.³⁷

Medical therapy has the advantage of being able to treat large areas with many lesions. The disadvantages of medical therapies include lengthy courses of treatment with irritation and discomfort. The US Food and Drug Administration (FDA) has approved 4 medications for the treatment of actinic keratoses. These are topical 5-fluorouracil (5-FU), 5% imiquimod cream, topical diclofenac gel, and PDT with topical delta-aminolevulinic acid.^38,39,40  

• The most experience in topical therapy for actinic keratoses is with 5-FU, known to inhibit thymidylate synthetase and cause cell death in actively proliferating cells.⁴¹ Several formulations are available, including a 5% cream or solution, a 2% solution, a 1% cream or solution, and, most recently, a micronized 0.5% cream.³⁸ Although not well studied, efficacy among the various formulations does not seem to differ significantly.^42,43
  • The most popular formulation is the 5% cream, which is applied twice daily for 1 month. During the treatment phase, the lesions become increasingly erythematous and cause discomfort; small subclinical lesions become visible. This treatment can be temporarily disfiguring, with erythematous ulcerations and crust formation. However, if the patient completes the treatment, the lesions usually heal within 2 weeks of stopping treatment, the complexion is smooth, and the actinic keratoses are improved.
  • The 0.5% micronized cream was developed to increase tolerability because inflammation and discomfort can be a limiting factor in the use of topical 5-FU. The 0.5% micronized cream is applied once daily for 1 month.

Actinic keratosis during treatment with topical 5-fluorouracil. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

Actinic keratosis right after treatment with topical 5-fluorouracil. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

• Imiquimod is a topical medication that up-regulates a variety of cytokines, which, in turn, invoke a nonspecific immune response (interferons, natural killer cells) and a specific immune response (T cells). It is applied 2-3 times a week for up to 4 months, although generally 1 month is sufficient.⁴⁴ Reaction to the drug is idiosyncratic, with some patients barely reacting and others developing marked inflammation. Subclinical lesions previously not appreciated may become inflamed during therapy. In patients with a brisk inflammatory response, dosing is reduced to twice or even once a week, with preservation of therapeutic efficacy but increased tolerability. Experimental evidence suggests patients may develop T-cell memory after treatment with this drug and thus may be less likely to develop new actinic keratoses in the future. Imiquimod 5% cream has also been shown to be safe and effective in transplantation patients.^45,46
• Topical diclofenac sodium 3% gel is a nonsteroidal anti-inflammatory drug approved by the FDA for the treatment of actinic keratosis. Its mechanism of action against actinic keratoses is unknown. It is effective therapy when applied twice a day for 3 months. A shorter course of therapy is dramatically less effective. Its chief advantage is that it produces little-to-no inflammation and thus is very well tolerated. Diclofenac therapy after cryosurgery has also been shown to produce complete lesion clearance in a higher number of patients compared with cryosurgery alone (64% vs 32%, respectively).⁴⁷
• 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.⁴⁸
  • Patients experience pain, similar in scope to the pain resulting from topical 5-FU, in the areas treated. The treated lesions may become erythematous and crusted. One treatment with PDT appears to be as effective as topical 5-FU therapy.⁴⁹
  • Immunosuppressed patients may also benefit from PDT in the prevention of nonmelanoma skin cancers.⁵⁰
  • When used with light sources that have a cosmetic benefit by themselves, such as the pulsed dye laser or intense pulsed light devices, a cosmetic benefit may be seen from the use of topical PDT beyond that of actinic keratosis eradication. Compared with other destructive therapeutic options such as cryotherapy, PDT may offer better cosmetic results and higher patient preference.^50,51
  • An unknown parameter in the use of topical PDT is the optimal incubation time following application of the topical aminolevulinic acid before light exposure. A second unknown parameter is the optimal light source to use for this treatment. Ongoing studies are addressing these issues.^50,52

Surgical Care

The goal of surgical therapy is complete eradication of the actinic keratoses, usually by physical destruction, with limited-to-no damage to surrounding healthy tissue. When the diagnosis is unclear and an invasive tumor is possible, biopsy is indicated. However, biopsy generally leaves a scar.

• Cryosurgery refers to use of a cryogen to lower the temperature of the skin and produce cell death. The most common cryogen used is liquid nitrogen, with a temperature of -195.8°C. Keratinocytes die when exposed to approximately -40 to -50°C. Other structures in the skin, such as collagen, blood vessels, and nerves, are more resistant to the lethal effects of cold than keratinocytes. Melanocytes are more sensitive than keratinocytes; thus, cryosurgery often leaves white spots. This technique has not been studied in a scientific fashion until 2004, when it was demonstrated to produce an overall clearance rate of 67%-88%.^51,53
• Lesions suggestive of invasive cancer may be treated with curettage, shave excision, or conventional excision, all of which provide a sample for histologic evaluation. These treatments require local anesthesia, produce a wound that requires time to heal, and are likely to scar.
• Cosmetic resurfacing procedures, in which the entire epidermis is removed, sometimes with some portion of the dermis, are effective for actinic keratosis eradication. Cosmetic resurfacing procedures include medium and deep chemical peels, dermabrasion, and ablative laser resurfacing.^54,55,56 All of these are cosmetic procedures unlikely to be covered by insurance, all carry the risk of scarring and infection, and all require experience and expertise on the part of the dermatologic surgeon. They are highly unlikely to be performed solely for actinic keratosis therapy.

Diet

One study has suggested that a low-fat diet in humans leads to greater resolution of existent actinic keratoses and the development of fewer new ones during the study period.¹⁷

Activity

Instruct patients to practice sun safety, such as the use of sunscreen and protective clothing, and to limit outdoor activity from 10:00 am to 3:00 pm.³⁷

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antineoplastic Agent, Topical

DOC is topical 5-FU lotion or cream, which inhibits cell growth and proliferation.

Fluorouracil (Fluoroplex, Carac, Efudex)

Used topically for management of actinic keratoses. Interferes with DNA synthesis by blocking methylation of deoxyuridylic acid via inhibition of thymidylate synthetase and, subsequently, cell proliferation. For lesions on bald scalp or extremities, longer treatment is often necessary.

Dosing

Adult

Apply topically to affected areas bid for approximately 2-6 wk (has been used as long as 12 wk in some cases)

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; pregnancy

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Inflammatory reactions may occur with occlusive dressings; porous gauze dressing may be applied for cosmetic reasons, without an increase in reaction; patients should expect inflammatory reaction with crusting; application to mucous membranes may cause increased inflammation and ulceration; exposure to UV rays (ie, sunlight) may increase intensity of the reaction

Immunomodulator, Topical

Investigation of imiquimod demonstrates it induces interferons alpha and gamma, TNF-alpha, and interleukin 12, among other cytokines. Studies using 5% cream in mice showed significant induction of interferon alpha at the site of application, occurring as early as 2 h after treatment. At 4 h after application, increases in interferon alpha mRNA levels were found, indicating an increase in transcription. Cytokine up-regulation is thought to be activated by imiquimod binding to toll-like receptor VII.

Imiquimod (Aldara)

Immune response modifier thought to produce a nonspecific anti–actinic keratosis response; interferon, natural killer cells) and a specific immune response (cytotoxic T cells). Indicated for clinically typical, nonhyperkeratotic, nonhypertrophic actinic keratoses on the face or scalp.

Dosing

Adult

Apply no more than 1 packet to defined area of face or scalp 2 times/wk hs for 16 wk; apply to dry skin (at least 10 min after washing face) and leave on for approximately 8 h; then, wash area with mild soap and water

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid exposure to sunlight or artificial tanning devices; regular use of sunscreen is encouraged; avoid contact with lips, eyes, or nostrils; common adverse effects include erythema, edema, vesicles, erosion or ulceration, weeping, exudate, flaking, scaling, dryness, scabbing, or crusting

Photosensitizing Agent, Topical

Administered in combination with PDT.

Aminolevulinic acid (Levulan), Methyl aminolevulinate cream (Metvixia)

Porphyrin precursor used in combination with narrow-band, red-light illumination for nonhyperkeratotic, nonpigmented actinic keratoses. When used with PDT, accumulation of photoactive porphyrins produce a photodynamic reaction that results in a cytotoxic process dependent upon the simultaneous presence of oxygen.
PDT with aminolevulinic acid is a 2-stage process involving application of the solution followed by illumination with blue light 14-18 h later; treatment may be repeated every 8 weeks.
Levulan: Topical solution 20% intended for direct application to individual lesions diagnosed as actinic keratosis and not to perilesional skin. Application should involve either scalp or face lesions, but not both simultaneously. Recommended treatment frequency is 1 application and 1 dose of illumination per treatment site per 8-wk treatment session. Each Levulan Kerastick should be used for only 1 patient.

Dosing

Adult

After lesion preparation, apply 16.8% cream to lesion and occlude for 3 h; remove excess cream with normal saline, then illuminate with Aktilite CL128 lamp; repeat treatment session after 1 wk

Pediatric

<18 years: Not established

Interactions

Data limited; known photosensitizing agents (eg, tetracyclines, fluoroquinolones, sulfonamides, diuretics, retinoids, sulfonylureas) may increase photosensitivity reaction

Contraindications

Documented hypersensitivity to porphyrins or components of cream, including peanut and almond oils; cutaneous photosensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

For topical use only; not for ophthalmic, oral, or intravaginal use; health care professionals administering treatment must wear nitrile gloves at all times during the procedure; patients and health care providers must wear protective eye wear during light therapy; common adverse effects include contact sensitization (>10%), which may include erythema, pain, burning and discomfort, pruritus, scab formation, crusting, erosions, edema, and exfoliation of skin

Nonsteroidal Anti-inflammatory Drug, Topical

Diclofenac (Solaraze)

Designated chemically as 2-[(2,6-dichlorophenyl) amino] benzeneacetic acid, monosodium salt, with an empirical formula of C₁₄ H₁₀ Cl₂ NO₂ Na. One of a series of phenylacetic acids that has demonstrated anti-inflammatory and analgesic properties in pharmacological studies. Believed to inhibit the enzyme cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Can cause hepatotoxicity; hence, liver enzyme levels should be monitored in first 8 wk of treatment.
Used topically as a keratolytic agent to treat actinic keratoses.

Dosing

Adult

Apply topically to affected area(s) bid for 60-90 d

Pediatric

Not indicated

Interactions

Cidofovir

Contraindications

Documented hypersensitivity; administer with caution to patients with aspirin triad; triad typically includes asthmatic patients who experience rhinitis with or without nasal polyps or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Teratogenicity has not been established in humans; in animals, studies revealed reduced fetal weights and growth and reduced fetal survival at maternally toxic levels.

Follow-up

Further Outpatient Care

• If the lesions do not respond to topical therapy, they can be treated with cryotherapy with liquid nitrogen spray for 5-20 seconds.⁵³ Lesions become irritated and ulcerate, and eventually the diseased pathology is sloughed from healthy skin.⁵³
• A biopsy of more advanced lesions that are indurated should be performed to rule out an invasive carcinoma.³³

Deterrence/Prevention

• The development of these lesions is directly proportional to sun exposure. Actinic keratoses can be reduced or delayed by using sunscreens and reducing sun exposure.³⁷   
  • Patients should limit recreational exposure, and those who work outdoors should consider making adjustments in their work-related sun exposure.
  • For patients forced to undergo sun exposure, recommend applying a sunscreen of sun protection factor (SPF) 30 or more and wearing protective clothing daily.³⁷

Complications

• Lesions may progress into invasive squamous cell carcinomas. A biopsy should be performed on nodular, indurated, or unresponsive lesions.³³

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.^1,7 Patients with extensive involvement unresponsive to cryosurgery and topical therapy may benefit from skin resurfacing by dermabrasion,⁵⁶ chemical peeling, or laser resurfacing.⁵⁵

Patient Education

• Encourage patients to wear sunscreens, to limit sun exposure, and to adjust their hobby or profession to decrease sun exposure.
• For excellent patient education resources, see eMedicine's Skin, Hair, and Nails Center. Additionally, see eMedicine's patient education article Skin Cancer.

Miscellaneous

Medicolegal Pitfalls

• A lesion that is observed by the physician over the long term and is allowed to progress to an invasive squamous cell carcinoma that may become metastatic and cause a fatality is a medicolegal pitfall. However, metastasis is unlikely except in neglected, large tumors, so in general, a dangerous invasive squamous cell carcinoma will be obvious. As always, biopsy should be performed on enlarging nodular lesions.

Multimedia

Media file 1: Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

Media file 2: Actinic keratosis during treatment with topical 5-fluorouracil. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

Media file 3: Actinic keratosis right after treatment with topical 5-fluorouracil. Courtesy of Hon Pak, MD, and reviewed by Ross Levy, MD.

Media file 4: Erythematous, scaly lesions on the temple area, typical of actinic keratosis.

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Keywords

actinic keratosis, solar keratosis, carcinoma in situ, carcinoma in-situ, premalignant skin lesions, sun-related growth, hyperkeratosis, skin cancers, telangiectasias, elastosis, pigmented lentigines, acanthosis, parakeratosis, dyskeratoses, Fitzpatrick type I and II skin, multiple erythematous keratoses

Contributor Information and Disclosures

Author

James M Spencer, MD, Professor of Clinical Dermatology, Mount Sinai School of Medicine, New York; Private Practice, Spencer Dermatology, St Petersburg, Florida
James M Spencer, MD is a member of the following medical societies: American Academy of Cosmetic Surgery, American Academy of Dermatology, American College of Mohs Micrographic Surgery and Cutaneous Oncology, American Dermatological Association, American Medical Association, American Society for Dermatologic Surgery, American Society for Laser Medicine and Surgery, and International Society for Dermatologic Surgery
Disclosure: Graceway Pharmaceutical Honoraria Speaking and teaching; Sanofi Aventis Honoraria Consulting

Coauthor(s)

Amy Lynn Basile, DO, MPH, Sun Coast Hospital/Largo Medical Center, Largo, Florida
Amy Lynn Basile, DO, MPH is a member of the following medical societies: American Medical Association, American Osteopathic Association, and American Osteopathic College of Dermatology
Disclosure: Nothing to disclose.

Medical Editor

Kelly M Cordoro, MD, Fellow and Clinical Instructor, Department of Pediatric Dermatology, University of California at San Francisco; Assistant Professor (On Educational Leave), Assistant Program Director for Resident Medical Education, Department of Dermatology, University of Virginia School of Medicine
Kelly M Cordoro, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Association of Professors of Dermatology, Dermatology Foundation, Medical Society of Virginia, National Psoriasis Foundation, Society for Pediatric Dermatology, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Mary Farley, MD, Dermatologic Surgeon/Mohs Surgeon, Anne Arundel Surgery Center
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, James Fulton Jr, MD, PhD, to the development and writing of this article. The authors and editors of eMedicine also gratefully acknowledge the contributions of previous Chief Editor, William D. James, MD, to the development and writing of this article.

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