Actinic Keratosis and Squamous Cell Carcinoma: Photodamage in Progress

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1. A 70-year-old man presents with a scaly rough patch on his bald scalp. Based on the image above, what is the most likely diagnosis?

A. Eczema

B. Rosacea

C. Squamous cell carcinoma (SCC)

D. Actinic keratosis (AK)

E. Wart

Answer and question 2 on next page.

Answer: D. Actinic keratosis

2. T or F: Actinic keratoses (AKs) can sometimes be diagnosed by palpation before they are clinically visible.

A. True

B. False

Answer and question 3 on next page.

Answer: A. True

3. T or F: AKs are the most common epithelial pre-cancer in people.

A. True

B. False

Answer and discussion on next page.

Answer A. True

Discussion

Actinic keratosis (AK), also known as solar keratosis, is the most common type of epithelial pre-cancer lesion seen in clinical practice. AKs are present on chronically sun exposed areas of the body-mostly the scalp and the face (including the lips), neck, upper trunk, and extremities. The populations most at risk for developing AK are older individuals (50+ years of age) with very fair skin type (Fitzpatrick types 1-2) as well as those with a history of increased sun exposure. The lesions begin as small, rough spots and have a sandpaper-like texture which may sometimes be appreciated by palpation before they even become visible. With time the lesions can enlarge and become erythematous and scaly. Most of the lesions are small (3- to 10-mm), however some can reach several centimeters in diameter. Lesions can resolve spontaneously, especially small ones, but many AKs persist or continue to grow and some will progress to become squamous cell carcinoma in situ (SCC IS) or invasive SCC.

The clinical diagnosis of AKs can be challenging. Lesions can be subtle, small, with scale and indistinct borders on a background of dispigmentation, wrinkling, and telengiectasia associated with sun damage. Lesions typically accumulate in the highest density on skin surfaces that receive the highest sun exposure, ie bald scalp, tops of the ears, upper forehead, nasal bridge, dorsal surface of the hands, and extensor surface of the forearms. This accumulation is referred to as field cancerization and implies DNA damage to the cells in the entire affected skin field. This is important to consider when offering treatments for AKs, since some interventions are designed to address the entire field, while others spot-treat individual lesions.

There are several subtypes of AKs which are most easily differentiated by histology:

 â–º Hyperkeratotic (hyperplastic) AKs are papules or plaques on a red base with palpable scale and crust.

 â–º Lichenoid AK is grossly very similar to hyperkeratotic AK, but has more clinical redness and histological inflammation.

 â–º Atrophic AKs, similar to lichenoid AKs, clinically cannot be easily distinguished from the classic AKs, but histology demonstrates an atrophic epidermis.

More facts about AKs on next page.

AKs can become thickened to form cutaneous horns, which cannot be clinically distinguished from SCCs and should be biopsied.¹

Pigmented AKs often appear as hyperpigmented or reticulated lesions. They can simulate reticulated seborrheic keratosis or lentigo maligna and may require biopsy for diagnostic confirmation.

Actinic cheilitis is a form of AK present on the lower lip of individuals with a history of chronic sun exposure. Since SCC of the lip can be more aggressive than SCC in other settings, actinic cheilitis should be treated and followed with extra care.

Look carefully at the images below.

Figure 1 depicts a rough non-indurated patch on the left cheek of a woman with severe sun damage and a scar from a previous Moh's surgical exicision of skin cancer.

Figure 2 shows an indurated rough papule of relatively new onset on the what surface of whose hand?

4. Which of these is actinic keratosis and which is a squamous cell carcinoma? 

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Answer and discussion on next page.

Answer: Figure 1. Actinic keratosis and
Figure 2. Squamous cell carcinoma

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The AK-SCC continuum

AKs may do one of the following: they may regress, they may be static, or can progress to invasive SCC. SCC in situ, also known as Bowen’s disease, can develop de novo or from pre-existing AKs. A 2009 study found that 65% of primary SCC lesions arose from existing AK lesions and the risk of progression from AK to SCC, in situ and invasive, was 0.60% within 1 year.² The clinical presentation of SCC is very similar to AK, therefore it is difficult to differentiate between the two simply by inspection. SCC in situ presents as erythematous scaling papule or minimally raised plaque on the sun exposed skin, mainly in older individuals. The distribution of SCC, like AKs, involves areas of the body with the highest sun exposure. One important clue in visual inspection and differentiation between SCC and AK is the size of the lesion. Generally AK lesions tend to be smaller than SCC lesions. Invasive SCC typically is a tender, enlarging hyperkeratotic lesion that may become nodular and ulcerate.

5. Which of the following is NOT a treatment for actinic keratosis?

A. Surgical excision

B. Topical 5-fluorouracil

C. Ketoconazole

D. Imiquimod

E. Retinoids

F. Ingenol mebutate

G. Cryotherapy

Answer and discussion of treatment for AK on next page.

Answer: C. Ketokonazole is not a treatment for AK

Treatment of AK

Although most of AK lesions do not progress to SCC, they are often treated to decrease chances of progression to SCC, and also to help distinguish between static lesions and lesions of greater malignant potential. The treatment options available for AK form 2 groups:

 â–º Destructive therapies, ie, surgical excision, cryotherapy, and dermabrasion

 â–º Medical therapies, including  topical 5-fluorouracil (5-FU), topical immune response modifier (imiquimod), topical ingenol mebutate, diclofenac, retinoids, as well as photodynamic therapy.³

The wide range of treatments available for AKs gives patients and physicians an opportunity to individualize therapy, taking into consideration factors such as number of lesions present; patient’s preference for receiving treatment in the outpatient setting vs administered at home; as well as patient’s tolerance of side effects. The destructive therapies, especially cryotherapy and shave excision followed by electrodessication, are used most often for single lesions. Cryotherapy is most popular due to its effectiveness, short duration, and limited cost. The treatment is delivered to an isolated lesion by spray, cotton tip applicator, or with a cryoprobe, typically in an outpatient setting.

Field therapies are more suitable for patients with field carcinogenesis: multiple lesions both clinically evident and subclinical where treatment of all lesions is desirable. Among these therapies application of topical 5-FU has been most widely used. Regimens are varied to increase tolerability. Imiquimod may have the highest cure rate of the topical field treatment options. Other therapies include a short 3-day treatment with ingenol mebutate to increase compliance.⁴ Topical diclofenac seems to be associated with the lowest level of irritation; however, it also has the lowest response rate.

Next: Risk Factors for Squamous Cell Carcinoma

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Risk factors for SCC

Exposure to UV radiation, either natural or artificial, is the most widely recognized risk factor for developing SCC. The studies investigating the risk of increased artificial UV exposure and SCC have determined an odds ratio of 2.5 among those who used tanning lamps.¹ The occurrence of SCC associated with UV exposure is especially high in individuals with very fair skin (Fitzpatrick types 1, 2). Transplant patients receiving chronic immunosuppressive therapy and those with autoimmune diseases are predisposed to increased SCCs. Human papillomavirus types 16,18, and other serotypes less commonly have been implicated in SCC. HIV positive patients with HPV (types 16 and 18) are at significantly increased risk for developing SCC, especially in the anogenital region. Other risk factors include exposure to chemicals like arsenic, polycyclic aromatic hydrocarbons and pesticides. The SCC lesions that are caused by arsenic are often multiple and develop on the non-sun-exposed areas of the trunk. Additionally, there is an increased risk for development of cutaneous SCC with scars, burns, and ulcers, which lead to chronic inflammation of the skin.

Besides the risk factors mentioned above, there are genetic syndromes, such as oculocutaneous albinism and xeroderma pigmnetosum, which have been associated with increased occurrence of SCC.¹

The incidence of SCC is highest in Caucasians and is associated with accumulation of UV exposure. The population with the highest prevalence is therefore expected to be mostly white, living close to the equator, and engaging in outdoors activities. Australia has the highest skin cancer incidence in the world with estimated incidence of SCC of around 1035 per 100,000 for men and 472 per 100,000 for women.⁵

Click on links below for other sections of this Special Report, Non-melanoma Skin Cancer: A Primer for Primary Care

Part 1: Introduction and Pre-test

Part 2: A Pearly-pink Lesion on a 68-year-old Woman's Face

Part 3: Three Suspicious Lesions on an Elderly Woman's Face

References:

1. Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. 2nd Edition. Mosby. 2007

2. Criscione et al. Actinic keratosis: natural history and malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115:2523-30.

3. Dreno B, Amici J, Basset-Seguin N, Cribier B, Claudel J, Richard M. Management of actinic keratosis: practical report and treatment algorithm from AKTeam expert clinicians. J European Acaad Derm Venerol. 2014; 28:1141-1149.

4. Lebwohl et al. Ingenol mebutate gel for actinic keratosis. NEJM. 2012;366:1010-9

5. Green A, Battistutta D, Hart V, et al. Skin cancer in a subtropical Australian population: incidence and lack of association with occupation. The Nambour Study Group. Am J Epidemiol. 1996;144:1034.