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Saturday, January 14, 2012

Actinic keratoses

Author : Suraj Venna, MD, FAAD Director, Melanoma Center Washington Cancer Institute 110 Irving Street, NW Washington DC 20010 (o) 202 877 2551

2009-07-20

Actinic Keratoses : pre cancerous skin lesions



Learn the basics of pre-cancerous skin lesions. Actinic Keratoses – Pre Cancerous Skin Lesions


Contents

Introduction

What are actinic keratoses and how are they related to skin cancer?

What do actinic keratoses look like?

Who gets actinic keratoses and what are the risk factors?

Is a biopsy needed to make a diagnosis of an actinic keratosis?

How are actinic keratoses treated?

Is there a way to prevent the onset of actinic keratoses?





Introduction

There are two basic categories of skin cancer for which people seek the care of a dermatologist: melanoma and non-melanoma skin cancer (NMSC). There are 55,000 cases of melanoma annually in the United States and nearly 1,000,000 cases of NMSC.  NMSC includes basal cell skin cancer, accounting for 80% of cases, and squamous cell skin cancer, accounting for 20% of cases. Melanoma skin cancer is the most dangerous, since it appears to have a greater ability to metastasize or spread from the skin to other body sites. NMSCs have a much lower risk of spreading from the skin to other body sites. Of the NMSCs, basal cell rarely spreads beyond the skin, however squamous cell does have a small but real risk of spread. In the United States, of the nearly 200,000 cases of squamous cell skin cancer annually, about 1% or 2000 people, die from metastatic squamous cell skin cancer.



This article examines actinic keratoses (AKs), which are pre-cancerous growths that can convert to squamous cell skin cancer in as many as 10% of the people who have AKs.



What are actinic keratoses and how are they related to skin cancer?

Actinic keratoses (AKs), also known as Solar Keratoses, are one of the most common reasons for a person to see their dermatologist.  AKs are precursor lesions to the squamous cell type of skin cancer and are considered pre-cancerous growths. AKs most commonly occur on sun exposed sites of fair skinned individuals. Although it is traditionally taught that 40% of squamous cell skin cancers (SCCs) begin as an AK, various studies over the last 20 years have determined a conversion rate of AKs to SCC to be 0.1% to 10% (1-3). The vast majority of patients who develop SCC are effectively treated. A small percentage of these patients, however, develop life-threatening spread beyond the skin.



AKs may resolve spontaneously, especially in those who use sunblock and limit sun exposure. Otherwise AKs may grow into SCCs. Having numerous AKs are indicative of excessive sun exposure. As such, AKs are markers for the development of all types of skin cancer, including melanoma and basal cell type (4-8).



What do actinic keratoses look like?

AKs are red, scaly growths or bumps, generally smaller than the eraser on a pencil, with a characteristic gritty, rough or prickly surface. As they are caused by sun exposure, they commonly occur on the scalp, ears, face, lips, neck, forearms and the backs of the hands (Figure 1 and Figure 2). Aside from their appearance, AKs are often asymptomatic, but they can become thick, bleed, and cause irritation or pain (Figure 3).
                  
                                     Figure 1

                                    Multiple rough lesions on the face and scalp of an elderly person.

                                    Also note AKs on the rim of the ear.
  
                       

                                    Figure 2

                                    Sun exposed area of the hand showing multiple actinic keratoses.




                                    Figure 3 
                                    Untreated, diffuse sun damage with thick actinic keratoses.



Who gets actinic keratoses and what are the risk factors?

About 10-20% of adults in the United States have AKs. These lesions are primarily caused by ultraviolet radiation from the sun and, if left untreated, can transform into SCC (Figure 4). AKs occur predominantly in the Caucasian population and correlate with the amount of sun exposure over one’s lifetime. People usually begin to develop AKs in their forties and fifties, although AKs may also be seen in people in their twenties, which may reflect the fact that nearly 80% of sun damage to the skin has accumulated by the time an individual is 18 years old. AKs are more common in men than women and are more likely to occur on someone who has an outdoor occupation. The highest frequency of AKs occurs in populations closest to the equator, since these areas are subjected to more direct and intense sunlight. The highest incidence of skin cancer in the world is in Australia where nearly 40% of adults have AKs.

                                    Figure 4

                                    A large squamous cell carcinoma on the cheek.




People who tend to burn and have a minimal tanning response, also known as Fitzpatrick skin-type I and II, generally are more susceptible to AKs and skin cancer compared to darker complexioned people. The reason for this difference is based on the function of pigmentation in the skin.  Skin pigment acts as a layer of protection against the harmful rays of the sun. Due to this protective role of pigment, skin cancer and AKs are rare in darker skinned people. The ability of our bodies to combat cancer is also a function of our age and the robustness of our immune system. Thus, individuals who are immunosuppressed are at higher risk of AKs and skin cancer. Examples of immunosuppressed states include the following: people taking medications for cancer or autoimmune diseases, organ transplant recipients, and individuals with acquired immunodeficiency syndrome (AIDS). 



Is a biopsy needed to make a diagnosis of an AK?

The majority of AKs are diagnosed clinically (through an observation by a physician); very few are confirmed with a biopsy. The diagnostic accuracy for clinically identifying an AK correctly is in the range of 74-94% (5,10,11). Nevertheless, when the growth is large, grows rapidly, causes pain, or has been treated multiple times and is not resolving it would be prudent to biopsy growths to rule-out skin cancer.



Most physicians can diagnose an actinic keratosis, although the diagnosis is most frequently made by dermatologists. Of the 127 million office visits to dermatologists over a four-year period, 14.6 million or 11.5% were for the evaluation and treatment of AKs (9).



How are actinic keratoses treated?

It is important to realize that AKs can be completely and effectively treated in a variety of ways. Since AKs are readily identified by physicians, biopsies are not routinely performed and the physician simply proceeds with treatment. The type of treatment that your physician may advocate will depend on the location of these lesions, the number of AKs, the size of the AKs, as well as the medical history of the patient and age. Most therapies are well tolerated.  They can be broadly divided into surgical and medical treatments as seen in the table below. The most common treatment is with cryosurgery, followed by medicated creams and in some instances a combination approach.



Medical Surgical
Topical chemotherapy Cryosurgery
Topical immunomodulators Laser resurfacing
Chemical peel Dermabrasion
Topical nonsteroidal anti-inflammatory Curettage
Photodynamic therapy   Excisional removal



Cryosurgery

The most common treatment for AKs is cryosurgery using liquid nitrogen (LN2) at a temperature of about -195 degrees celsius. The LN2 is applied either with a Q-tip, metal surgical instrument or, most commonly, with an insulated spray thermos. Usually a lesion is treated twice, with each freezing cycle lasting a few seconds. A transient stinging sensation develops, after which the area becomes red and may blister. Over the course of days to weeks, the lesion will crust over and scale off or at least will decrease in size. Some patients will develop whitish scars at treated sites, which in some instances can be permanent. The use of LN2 is best suited for those who have less than 10-15 lesions. Beyond this number of lesions, treatments that can elicit more of a field effect are used. Generally, AKs should revert or disappear after 2 treatments (each treatment consisting of two rounds of LN2). If a lesion continues to grow in spite of treatment, it is prudent to have this lesion biopsied or sampled, because it may have transformed into squamous cell skin cancer or may be something other than an AK or SCC (5).



Medicated creams

In patients with many AKs, a medicated cream may be the best approach since this will allow treatment of a greater area and cover many lesions (>10 -15). The other benefit to topical treatment is their ability to halt the aberrant growth of single, atypical cells in the skin that constitute an AK, even though they don’t always form an obvious growth or lesion. However, these single or few atypical cells will succumb to the effects of topical treatment; this is known as the field effect.



Topical chemotherapy: fluorouracil

Atypical cells, as found in AKs, divide faster than normal healthy skin cells. This is the basis for the action of fluorouracil: it becomes incorporated into cells that are dividing rapidly and once in the cell, prevents the cell from further divisions, ultimately eradicating this pre-cancer growth. Fluorouracil is a highly effective, FDA approved treatment of AKs and has been in use for several decades. Most formulations are used once or twice per day for four to six weeks and the patient is educated on the different phases that the skin will endure. During weeks one and two, there will be irritation, redness, stinging, crusting and burning. By week three, most patients will go through an exfoliation phase during which most of the AKs and damaged skin flakes off and new healthy skin cells replenish the treated areas. Most patients also notice redness and inflammation on parts of the skin where they have no obvious AK lesion. This is because of the aforementioned field effect, where fluorouracil becomes incorporated into unhealthy skin cells that have not yet formed a lesion or growth. Patients should be forewarned that they will have a significant response especially during the first couple of weeks of application.



Topical immunotherapy: imiquimod

Imiquimod is a cream that was initially developed and approved for the treatment of genital warts. It was subsequently approved by the FDA for treatment of AKs in 2004. This cream stimulates the local immune system in the skin to destroy the atypical cells forming AKs. As with other topicals, patients will experience redness, burning and scaling. A small percentage of patients can also develop flu-like symptoms. The duration of treatment is up to 16 weeks and patients should apply the cream 2 or 3 times per week. Compared to fluorouracil, the response to imiquimod is not as predictable: some patients have intense redness and scaling while others have minimal or no response. This may be a function of the individual patient’s immune system.



Topical nonsteroidal anti-inflammatory (NSAIDS)

NSAIDs are a familiar class of medications, examples of which are ibuprofen (Advil, Motrin) and naproxen (Alleve, Naprosyn). Diclofenac gel is a topical NSAID approved for the treatment of AKs. The mechanism of action is not entirely clear, but may in part be related to the medication blocking nutrients that atypical cells require to grow. Diclofenac gel is applied twice daily for 60-90 days and, as with other topicals, the most common side effect is local irritation. People allergic to the various pill forms of NSAIDs should not use diclofenac.



Photodynamic therapy (PDT)

A light-sensitive topical solution is applied to the affected area of skin and gets absorbed into the atypical skin cells. The chemical applied is called 5-aminolevulinic acid (5-ALA), a compound found in red-blood cells that is a precursor to hemoglobin (the oxygen carrying component of blood). After a prescribed time period (few hours to overnight), the skin is exposed to a special light that activates 5-ALA, ultimately destroying the actinic keratosis. PDT is thought to offer more selective destruction over other topical modalities with less damage to surrounding normal skin. Most patients can see a dramatic improvement even after one treatment.


The other types of surgical and medical treatments in the above table are not used as commonly, but offer both physicians and patients a wide array of options. Curettage involves the use of a special instrument, the curette, to scrape off the AK, which can then be sent for biopsy evaluation. This is effective for thicker AKs and is often followed by cautery which stops bleeding that may be associated with AK removal.  Excision involves numbing the area with local anesthesia then taking a blade and cutting the lesion out, repairing the skin with sutures. The specimen is then sent for biopsy evaluation. This technique will offer complete removal of the lesion, although will leave a scar and is reserved for AKs that are thick and unresponsive to LN2, or when the physician believes the lesion may have already turned into squamous cell skin cancer. Chemical peels, dermabrasion, and lasers are also used for the treatment of AKs. These approaches are based on superficial and deeper skin destruction with removal of the top layer of skin, the epidermis, and sometimes the next layer of skin called the dermis. Since AKs are atypical cells that grow within the epidermis, these resurfacing approaches can be effective, although they are not routinely used for this purpose.



Is there a way to prevent the onset of actinic keratoses?

Since AKs are sun-induced growths, limiting sun exposure is a way to minimize the number of AKs that one gets. A study in the New England Journal of Medicine found that regular sunscreen use prevents the development of AKs, reduces the number of existing AKs, and is associated with a potential risk reduction in skin cancer development (11).

An intriguing study examined the effects of a low-fat diet on the subsequent incidence of AKs in a population of patients who have had skin cancer (12). These people were followed for a two year period: one group had a diet consisting of 40% fat calories while the intervention group was restricted to 20% fat calories. Over the two year period, the patients on the lower fat diet developed on average three AKs compared to 10 AKs in the unrestricted group. This is an interesting study, but limited due to the overall number of patients and warrants further validation.

            The key, then, to prevention is to limit unnecessary and dangerous sun exposure by protecting your skin through the use of protective sun clothing and sunscreens, avoiding sunburns, and limiting outdoor activity during peak sun hours (10am-2pm).



For more information:









http://www.aad.org/media/background/factsheets/fact_sunscreen.htm





 

References 

1.      Marks R, Foley P, Goodman G, et al. Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatology 1986; 115:69-55

2.      Marks R, Rennie G, Selwood TS. Malignant transformation of solar keratoses to squamous cell carcinoma in the skin: a prospective study. Lancet 1988; 795-7

3.      Dobson JM, DeSpain J, Hewett JE, Clark DP. Malignant potential of actinic keratoses and the controversy over treatment: a patient oriented perspective. Archives of Dermatol. 1991; 127: 1029-31

4.      Green A, Battistutta D. Incidence and determinants of skin cancer in a high risk Australian population. Int J Cancer 1990; 15:356-61

5.      Marks R, Rennie G, Selwood TS. The relationship of basal cell carcinoma and squamous cell carcinoma to solar keratoses. Archives of Dermatology 1988; 1124:1039-42

6.      Bataille V, Sasieni P, Grulich A, et al. Solar Keratoses: A Risk Factor for Melanoma but Negative Association with Melanocytic Nevi. Int J Cancer 1998; 78:8-12

7.      Green AC, O’Rourke MG. Cutaneous melanoma in association with other skin cancers. J Nat. Cancer Inst. 1985; 74:977-980

8.      Dubin M, Moseson M, Pasternak BS. Epidemiology of malignant melanoma: pigmentary traits, ultraviolet radiation and the identification of high-risk populations. Recent Results Cancer Reasearch 1986;102:56-75

9.      Feldman S, Fleischer AB, McConnell C. Most common dermatologic problems identified by internists: 1990-94; Archive of Internal Med 1998; 158:726-30

10.  Venna S, Lee D, Stadecker M, Rogers G. Clinical Recognition of Actinic Keratoses: How Good Are We? Archive of Dermatol 2005;141:507-09

11.  Thompson S, Jolley D, Marks R. Reduction of Solar Keratoses by Regular Susncreen Use. NEJM 1993;329:1147-1151

12.  Black H, Herd A, Goldberg L et al. Effect of a Low-Fat Diet on the Incidence of Actinic Keratoses. NEJM 1994;330:1272-75