Despite the benign appearance of actinic keratosis, the lesions can be pre-cancerous, making diagnostic vigilance very important for podiatric physicians. Accordingly, this author reviews current concepts in the diagnosis and effective treatment of actinic keratoses.
Actinic keratosis is a bit of a misnomer. Keratosis implies a benign condition but this is the only “keratosis” that can be a potential squamous cell carcinoma. Actinic keratosis (also known as solar keratosis or senile keratosis) is not as common on the feet and legs as it is on the head, neck and hands. However, this in no way means that we do not need to know everything we can know about this inconspicuous keratosis.
Actinic keratosis is a pre-cancerous lesion. Podiatrists need to be very vigilant because this lesion is pre-malignant. Progression can lead to hypertrophic actinic keratoses, in situ squamous cell carcinoma or invasive squamous cell carcinoma. It is not just thick skin. Regardless of what we call it, we must clearly recognize actinic keratosis for what it is, a potential squamous cell carcinoma.1
Pertinent Insights On Etiology
When abnormal cells grow in their normal place “in situ,” this means the cancer affects the uppermost layer of the skin and it does not affect the underlying healthy tissues (in situ from Latin for “in its place”). For example, carcinoma in situ of the skin, also called Bowen’s disease, is the accumulation of dysplastic epidermal cells within the epidermis only and it has failed to penetrate into the deeper dermis. Carcinoma in situ is a localized phenomenon with no potential for metastasis unless it progresses into the deeper tissues.
Chronic, long-term sun exposure results in genetic changes in epidermal keratinocytes and the development of various skin lesions ranging from actinic keratosis to skin cancer.2 Most individual actinic keratosis lesions do not become invasive cancers but the majority of invasive squamous cell carcinomas originate from actinic keratosis. The first curveball is that actinic keratosis can be pigmented or non-pigmented.3
Actinic keratoses are among the most common cutaneous intraepithelial neoplastic disorders.4 Some have proposed renaming actinic keratosis as “keratinocyte intraepithelial neoplasia.”4 Another opinion goes one step further and states that actinic keratosis are “in-situ intraepidermal squamous cell carcinomas,” which develop into invasive squamous cell carcinoma in 10 percent of the cases.4 A frequently occurring subtype is the hyperkeratotic/hyperplastic actinic keratosis.
Actinic keratosis occurs mainly on the sun-exposed (actinic) skin of fair-skinned middle-aged and older people. Outdoor workers and those who sit by the pool have a much higher risk.5 We have recently learned that sun exposure in childhood is particularly important as a risk factor.6
What To Look For In The Patient Presentation
Habif states two disheartening facts with respect to skin disease: a single entity can vary in its appearance and skin disease is dynamic and can change in morphology.7
Actinic keratosis is a common dermatologic condition that may regress, remain stable or progress to squamous cell carcinoma.8 When it comes to keratosis, you will see an excessive growth of cornified tissue. However, actinic keratosis does not always look the same. Actinic keratosis starts with the formation of rough, sandpaper-like, inconspicuous spots that are as small as a few millimeters or as large as 0.5 cm. They are frequently so small that we recognize them by touch rather than sight. The spots then develop into scaly plaques with a base that has a distinctive reddish color. However, some will be tan, pink or flesh-toned. They are usually flat or slightly raised.
That sounds like a lot of the skin conditions we see but there are key factors to keep in mind for differentiating these lesions. There is an extensive list of differential diagnoses to consider with actinic keratosis. The list includes seborrheic keratosis, dermatosis papulosa nigra, stucco keratosis, solar lentigines, cutaneous horn, basal cell carcinoma, disseminated superficial actinic porokeratosis, porokeratosis, lentigo maligna (melanoma) and Bowen’s disease. I will discuss these in more detail later in the article.
Recognizing The Diagnostic Benefits Of Dermoscopy And Skin Biopsy
In experienced hands, dermoscopy (also known as dermatoscopy or surface microscopy) is an ancillary dermatologic tool that can improve the accuracy of diagnosis for a variety of benign and malignant pigmented skin tumors.9 The use of dermoscopy can also assist with the diagnosis of non-pigmented or “pink” tumors (lesions) with the emphasis on blood vessel morphology and pattern.
Dermatoscopy helps in the diagnosis of many pigmented skin lesions such as seborrheic keratosis, pigmented basal cell carcinoma, hemangioma, blue nevus, atypical nevus and cutaneous melanoma. Dermatoscopy is 10 to 27 percent more sensitive than the clinical criteria of ABCD (asymmetry, border irregularity, color distribution and diameter) in the early diagnosis of cutaneous melanoma.4 Since one always reports novel dermatoscopic patterns and features for skin lesions, dermatoscopy is a continuously improving technique for dermatology.4 Accordingly, every podiatrist should acquire more in-depth knowledge relating to the dermatoscopic features and patterns of the benign and malignant skin lesions.
A skin biopsy is indicated to confirm the diagnosis and to rule out invasive squamous cell carcinoma for suspicious or more advanced lesions (i.e., those with more pronounced hyperkeratosis, increased erythema, induration or nodularity).10
Owing to the protective effects of a higher epidermal melanin concentration, skin cancers are much less common in people with darker skin. As with most types of cancer in pigmented skin including Hispanics, there is a lower incidence of actinic keratosis than in Caucasian skin. However, because of a lack of awareness of skin malignancies in people with dark skin, when malignancies do present, they are more advanced.11
A Primer On The Treatment Of Actinic Keratoses
Since there is no way to determine on clinical or histologic grounds which lesions will progress to invade the dermis and possibly metastasize, one should ensure prompt treatment for actinic keratosis.1 It can be difficult to distinguish actinic keratoses and early forms of squamous cell carcinoma or even other non-melanoma skin cancers so it is important to treat all actinic keratosis with the premise that full destruction of the lesions is tantamount.12
The goals of treatment are to eliminate visible actinic keratoses and treat subclinical (non-visible) actinic keratoses, minimizing their risk of progression to invasive squamous cell carcinoma while pursuing good cosmesis. One must remember that the foot and the leg are not the primary areas where actinic keratoses are visible. They are usually on the face, neck and hands, which are much more visible to others.
Few visible actinic keratoses (what we see as podiatrists) lead to the use of lesion-directed treatments. The locally destructive, mechanical ways to treat actinic keratoses include liquid nitrogen cryosurgery (the most common treatment), electrodessication and curettage and excision.13 Full-thickness surgical excisions and irradiation of actinic keratosis are generally discouraged.
With cryosurgery, the liquid nitrogen spray reaches a temperature of -5°C to freeze the epidermis and the upper dermis. In one study, there was a 100 percent cure rate at six weeks and side effects were limited to redness, blistering, crusting, oozing and ulceration.14 No recurrence of actinic keratosis, scarring or hypopigmentation had occurred.
The presence of multiple or subclinical (non-visible) actinic keratoses leads to the use of field-directed therapies, which provide for more complete treatment.15 Options include 5-fluorouracil (5-FU, Efudex), imiquimod, diclofenac (Voltaren, Endo Pharmaceuticals), ingenol mebutate (Picato, Leo Laboratories), photodynamic therapy, chemical peels and laser resurfacing. The 5–FU treatment appears to be the most common one. Rubbed gently onto the lesions once or twice a day for two to four weeks, 5-FU reportedly produces cure rates of up to 93 percent.16
Photodynamic therapy uses a light-sensitizing compound that preferentially accumulates in actinic keratosis cells where the appropriate wavelength of light can activate the therapy. Exposure to light of an appropriate wavelength generates oxygen free radicals and cell death results.
Emphasizing The Importance Of The Differential Diagnosis
As I noted earlier, clinicians must have a good understanding of the differential diagnosis with actinic keratosis. For a fabulous website on differentials, visit http://ddderm.blogspot.com/2008/10/red-scaly-diseases.html .
Seborrheic keratosis. Seborrheic keratosis is the most common benign tumor in older individuals.17 The incidence appears to increase with age. Seborrheic keratosis can also occur in younger individuals. Despite the name, these lesions do not have a sebaceous origin. Seborrheic keratoses resemble warts.
It is important to know that the morphology of lesions changes. They begin as slightly raised, skin color or light brown spots. They gradually thicken and take on a rough, warty surface. They slowly darken and may turn black. During this evolution, they may resemble actinic keratoses, warts and melanoma.18
Although the diagnosis of seborrheic keratoses is generally clinical, sometimes the differentiation between seborrheic keratoses and cutaneous melanoma may be difficult clinically. Seborrheic keratosis involves the blockage of pores, which prevents hair growth in the affected area. Many lesions have a comedo-like opening as well as hairpin blood vessels, fissures, sulci and gyri. The main difference of these two conditions is that actinic keratosis has the potential of becoming cancerous.17 Seborrheic keratosis is not known to develop into skin cancer. Variants of seborrheic keratoses include: solar lentigines, dermatosis papulosa nigra, stucco keratosis and lichenoid keratosis.
Seborrhoeic keratoses are also known as basal cell papillomas, senile warts or brown warts even though seborrheic keratosis is not a basal cell or a wart.17 Seborrheic keratoses are less common in populations with dark skin in comparison to those having white skin.
Dermatosis papulosa nigra. Approximately 35 percent of African-Americans develop this variant of seborrheic keratosis. This is also visible in those with pigmented skin.19 These lesions affect the face, especially the upper cheeks and lateral orbital areas. They are small, pedunculated and heavily pigmented with a minimal keratotic element. The onset of these lesions is generally earlier than that of ordinary seborrheic keratosis.
Stucco keratosis. Stucco keratosis is a type of seborrheic keratosis. One can mistake these lesions for warts on the lower extremity, specifically on the dorsum of the foot, ankles and legs. The name stucco keratosis derives from the “stuck on” appearance of the lesions. They appear to stick on to the skin like barnacles.18 Stucco keratosis is a benign lesion that one can remove by curettage or cryotherapy. It requires no topicals, light therapy or surgery.
Solar lentigines. Solar lentigines are also called age spots and liver spots, and increase in number with age. These lesions occur when melanin aggregates together in specific areas of the skin and gives an appearance of a tan, brown or black spot. Solar lentigines occur on skin that has had the most sun exposure over the years, such as the backs of hands, the tops of feet, the face, the shoulders and upper back.20 As with seborrheic keratosis, the chief cause is overexposure to the ultraviolet rays of the sun. These are round, flat, harmless patches of hyperpigmentation.
Cutaneous horn. This is a type of an actinic keratosis with the appearance of horns or sometimes of wood or coral. As the horn is composed of keratin, the same material found in fingernails, one can usually surgically remove the horn. Biopsy with confirmation is often necessary to rule out malignant changes. No clinical features reliably distinguish between benign and malignant lesions with cutaneous horns.21
Basal cell carcinoma. This is a nonmelanocytic skin cancer that arises from basal cells or the lower layer of the epidermis. It is visible as an erythematous, well-circumscribed macule with minimal scaling.
Disseminated superficial actinic porokeratosis. This is an inherited condition due to abnormal sun sensitivity that results in red–brown scaly spots with a distinctive fine thread rim known as a “coronoid lamellae.”22
Porokeratosis. Porokeratosis is a clonal disorder of keratinization characterized by one or more atrophic patches surrounded by a clinically and histologically distinctive hyperkeratotic ridgelike border called the cornoid lamella.23
Lentigo maligna (melanoma). Lentigo maligna is a subtype of melanoma in situ when it is confined to the epidermis. Lentigo maligna and lentigo maligna melanoma are associated with higher occupational exposure and lower recreational sun exposure.24
Bowen’s disease. Also known as squamous cell carcinoma in situ, Bowen’s disease is uncontrolled growth of abnormal cells arising in the squamous cells, which comprise most of the skin’s upper layers.25 Lesions from Bowen’s disease can masquerade as many other lesions. They can be scaly red patches, open sores or elevated growths with a central depression or warts, or they may crust or bleed. Women frequently get squamous cell carcinoma on their lower legs.26
In patients with dark skin types, squamous cell carcinoma may manifest as a pigmented Bowen’s disease lesion. Lesions from Bowen’s disease share similar features with other pigmented lesions including pigmented basal cell carcinoma and melanoma. The diagnosis of Bowen’s disease can be a challenge and biopsy is essential with these lesions.
While it is rare for actinic keratoses to appear on the feet and legs, it is important to recognize them when they occur. In your workup, you always want to ask the patient questions about their sun exposure. Do you sail? Do you have a boat? Do you spend a lot of time at the beach? Do you sunbathe? Age is important because time spent in the sun is additive. Actinic keratoses become much more common in people over the age of 50.6
Those whose immune defenses are weakened by chemotherapy, AIDS, organ transplantation or excessive ultraviolet exposure are less able to fight off the effects of the radiation and are thus more likely to develop actinic keratoses.
Although actinic keratosis is not one of the more common dermatoses that we see in a podiatry office, it can look like many of the dermatoses that we see including: psoriasis, lichen simplex chronicus, contact dermatitis, dyshidrotic eczema, verruca and fungal infections. Remember that this is not like the common dermatology dilemmas we see day in and day out, largely distinguishing among eczema, psoriasis and tinea. Actinic keratosis has the potential to cause cancer and significant morbidity.
Dr. Morse is the President of the American Society of Podiatric Dermatology. He is a Fellow of the American College of Foot and Ankle Surgeons, and the American College of Foot and Ankle Orthopedics and Medicine. Dr. Morse is board certified in foot surgery. He is on the Podiatric Residency Educational Committee at the MedStar Washington Hospital Center in Washington, D.C.
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