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Aktinic Keratosis (Pre-Cancer) - Information for Medical Professionals
Definition and Description
Actinic (solar) keratoses are extremely common (pre)malignant lesions occurring on chronically sun-exposed skin. They appear as rough, scaly erythematous patches with poorly defined borders. The prevalence increases with advancing age.
Incidence and Epidemiology
Actinic keratoses (AK) usually occur in fair skinned individuals over 45 years of age (skin type I or II). They rarely occur in type IV skin. The prevalence increases with advancing age. In Australia and in the southwestern US, younger people are affected more frequently, though.
Accurate figures on the prevalence and incidence are hard to obtain. AK is the most common precursor lesion for SCC in whites. Approximately 5-20% of AKs will transform into SCC within 10-25 years. The 1-year risk that AK lesion transform into SCC was estimated to 1.1% compared with the 10-year risk of 10.2%. By treating AKs the development of SCC can be prevented.
In the early decades, actinic keratoses are more prevalent in males, probably because of occupational and recreational sun exposure. In the age group from 50 to 86 years, the rates are more equal between the sexes.
Persons with occupational or recreational outdoors exposure, as well as those living at latitudes closer to the equator have higher incidence rates. Additionally, a 20th century change in fashion which dictates that a deep suntan in a fair-skinned person is associated with increased socio-economic status, has led to skin cancer and its precursors are now endemic in many places of the world.
Etiology and Pathogenesis
The most important risk factors for the development of actinic keratoses are a combination of genetic factors ("fair skin phenotype") and cumulative sun exposure, although they can also be caused by ultraviolet (UV) radiation from artificial sources or exposure to polycyclic aromatic hydrocarbons. It is assumed that ultraviolet radiation in sunlight produces changes in the genetic material of the epidermal cells, leading to proliferations of transformed, neoplastic keratinocytes.
Diagnosis
Careful inspection of the clinical findings may lead to the correct diagnosis. However, when the keratosis is pigmented it must be discerned from a seborrheic wart, which appears greasy on palpation and displays a regular granular texture. Flat or lichenoid actinic keratoses may resemble discoid lupus erythematodes, which is usually bright red in colour and has an easily detachable scale. Bowen's disease may also show a similar clinical picture, but it usually has a more erythematous base and a more irregular contour. Arsenic keratoses mainly occur in a different location, they prefer the palms and soles. If there is any doubt concerning the diagnosis, a histological examination should be performed.
Symptoms, Signs, and Course
The most common clinical presentation of an actinic keratosis is a red, scaling papule or plaque on a sun-exposed area (erythematous type). At first, it is only a few millimeters in size, but then it may grow several centimeters in diameter. The surrounding areas may show evidence of sun damage with blotchy pigmentation, telangiectases, and a yellowish discoloration.
The keratosis can progress into thickened or hypertrophic lesions (keratotic type). The reddened patches are no longer visible, but instead one sees a yellowish or dirty-brown hard, horny surface. The thickened lesions can progress into invasive squamous cell carcinoma
Other clinical variants of actinic keratoses present with the following characteristics:
- In cutaneous horns the keratinization is so prominent that a hyperkeratotic protuberance develops in a conical shape above the skin surface. A percentage of these lesions are actually squamous cell carcinoma.
- Lichen planus -like actinic keratoses occur on the extensor surfaces of the forearms and face and resemble the lesions in lichen planus. Pigmented actinic keratoses may resemble a scaling lentigo or a pigmented seborrheic keratosis.
Subjective symptoms are usually absent, though tenderness, itchiness and burning are sometimes reported.
Clinically, actinic keratoses observed over a period of time display 3 evolutionary possibilities:
- spontaneous regression
- persistence
- progression into invasive skin cancer, usually squamous cell carcinoma. But currently, no existing technology allows the clinician to distinguish between lesions that will clear, remain stable or progress to invasive carcinoma.
Actinic keratoses carry the risk of progression to invasive squamous cell carcinoma.
Prevention and Prophylaxis
Prevention of actinic keratosis is achieved through the use of effective UVA/UVB sunscreens, on the face, ears, neck, and other sun exposed areas of the skin. Broad-brimmed hats and sun protective clothing are also recommended. Prolonged sun exposure should be avoided, especially in children.
Differential Diagnosis
Complications
Actinic keratoses carry the risk of progression to invasive squamous cell carcinoma. Once this has occurred, the tumour may bleed, ulcerate, become infected, destroy anatomic structures or even spread to internal organs.
Treatment
Cryosurgery
Liquid nitrogen (-195.8°C), the most common cryogen, is applied using a spray device or a cotton tip applicator. The atypical cells are destroyed when the skin temperature is lowered to -50°C.
Advantages
- highly effective treatment
- a minimum of treatments (once or twice)
Disadvantages
- application causes discomfort and/ or pain to the patients
- side-effects such as blistering, erythema, edema, hypo- or hyperpigmentation
- risk of scarring
- infection may occur due to delayed wound-healing
- no standardization concerning duration and depth of freezing
- only appropriate for a few lesions or multiple scattered lesions
Curettage
Actinic keratoses can be scraped away with a curette. Afterwards, electrosurgery may be used to stop bleeding or to apply more damage to the area of the atypical cells. Aluminum chloride and ferric chloride are also used as hemostatics.
Advantages
Disadvantages
- local anesthetic required
- scar formation possible if the skin is too rigorously burned
- infection, hypo- and hyperpigmentation rarely occur
- less practicable with multiple or confluent lesions
Topical 5-fluorouracil
5-fluorouracil is a cytostatic agent which inhibits several enzymes in tumor cells, through interaction with RNA. It is applied locally in a thin layer and the lesion is subsequently covered with a plastic film. The treatment is repeated daily until the lesion erodes (usually a treatment length of 2 to 4 weeks is necessary).
Advantages
- efficacious treatment
- good cosmetic results
- treatment of large areas possible
- non-visible lesions can be treated
Disadvantages
- long treatment period (2 to 4 weeks)
- erythema, inflammation, erosions, and pain during entire treatment period
- usually low patient compliance
- cure rates depend on patient compliance
Photodynamic therapy (PDT)
Dermatological indications for PDT
- superficial non-pigmented epithelial tumors such as
- actinic keratosis
- Bowen`s disease
- superficial basal cell carcinoma
- superficial squamous cell carcinoma
- keratoacanthoma
- experimental: inflammatory dermatosis (eg. psoriasis vulgaris, acne)
- experimental: HPV-associated dermatoses (eg. warts, epidermodysplasia verruciformis)
The technique
PDT is based on the coaction of a photosensitizer, often a porphyrin-derivative, with visible light and oxygen. The photosensitizer specifically accumulates in rapid growing cells (e.g. tumor cells) and is activated by irradiation with visible light. The tumor destruction is caused by the formation of cytotoxic efficient reactive oxygen species, in particular singlet oxygen.
There are several photosenitizer presently in use (porphyrins, porphines, phthalocyanines, etc.) but most of them are not ideal for dermatological indications since they have to be administered systemically and cause general photosensitivity in patients. The most frequent used substance for PDT in dermatology is 5-ALA (d-aminolevulinic acid) and its derivatives. 5-Ala works as a prodrug that is metabolized intracellularly into protoporphyrin IX (PpIX) - the actual photosensitizer. PpIX will, when activated by light, generate singlet oxygen which will cause death of the tumor cells. Besides PDT the photosensitizer can also be activated by Wood light leading to fluorescence of the targeted lesion. In this way tumor lesions can be detected by photo diagnosis (PD).
The use
The standardized procedure for the treatment of AK involves the application of 20% ALA or its ester in a solution or cream. emulsion. 5-ALA then penetrates the skin and is metabolized into PpIX. ALA-uptake is higher by dysplastic cells and PpIX is synthesized more specifically in abnormal cells leading to a higher concentration of PpIX in abnormal than in healthy cells. After an application time of several hours the lesion will be exposed to light of a certain wavelength and intensity. In clinical trials the complete response rate of lesions was more than 90 % after one to two treatments. Furthermore, the cosmetic outcome was rated excellent or good in more than 90 % of patients. Consequentially 5-ALA PDT is at least as effective as standard treatments but with superior cosmesis.
For Irradiation of the leasion there are now several non-coherent light sources in use which differ mainly by their emission spectrum (red light, blue light, green light) and the irradiation area.
Advantages
- high efficacy
- excellent cosmetic results
- fast healing (approximately 2 weeks)
- treatment of large areas possible and multiple lesions in one session
- single/ twice treatment
- non-operative method
- topical administration without generalized cutaneous photosensitivity
- standardized therapy
Disadvantages
- a typical "PDT-response" such of local symptoms such as stinging, burning, itching, erythema and/or edema
- pain during irradiation may require anesthesia
- two-step process(application of photosensitizer and irradiation)
Other treatments
- Dermabrasion
- Chemical or cryosurgical peel
- Laser
- Salicylic acid
- Tretinoin or other topical retinoids
- Alpha hydroxy acids
- Topical masoprocol
- Excisional surgery
- Interferon
- Oral retinoids (in combination with 5-FU)
- Topical tubercidin
- Experimental: Imiquimod
Prognosis
Actinic keratoses may either disappear spontaneously, persist, or progress into invasive skin cancer with the capacity of metastasizing. Clinically, there is no possibility to distinguish between those lesions that will clear, persist or progress. Studies performed between 1991 and 1998 on the basis of thousands of keratoses distributed in a large population give us a risk for the progression of actinic keratoses to squamous cell carcinoma of between 6% and 12% per year.
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