Actinic Keratoses and Non-Melanoma Skin Cancer

Thomas W. McGovern, MD, and David J. Leffell, MD

Actinic Keratoses

The actinic keratosis (AK) is the earliest identifiable lesion that can eventually develop into an invasive squamous cell carcinoma (SCC). These lesions are diagnosed in 14 percent of all visits to dermatologists, following only acne and dermatitis in frequency. Debate swirls around the nomenclature for these lesions because some consider them to be pre-cancerous and others consider them to be a SCC confined to the lower portion of the epidermis. Actinic keratoses typically occur in fair-skinned individuals. In various northern hemisphere populations, 11 percent to 25 percent of adults have at least one, compared to 40 percent to 60 percent of adult Australians who live closer to the equator. One prospective study estimates that one AK/1,000/year transforms into SCC, whereas retrospective studies predict that from 5 percent to 20 percent of all untreated AKs will progress to SCC. AKs are typically produced by ultraviolet radiation, but ionizing radiation, arsenic, or polycyclic hydrocarbon exposure might also cause them. At least two prospective studies have demonstrated that sunscreen reduces the likelihood of developing more AKs.

On physical examination, the typical AK is a poorly demarcated, slightly erythematous papule or plaque found on sun-exposed areas such as the face, balding scalp, posterior neck, and dorsal upper extremity (Figure 1, Figure 2, Figure 3). Characteristically, AKs feel rough or gritty and might be difficult to see. Therefore, palpation of high-risk areas under an intense light source is essential to accurate diagnosis. Microscopically, one sees large keratinocytes with atypical nuclei in the lower portion of the epidermis. Liquid nitrogen, 5-fluorouracil cream, trichloroacetic acid, electrodesiccation and curettage, and CO2 laser all can eradicate AKs. Two newer treatment modalities include photodynamic therapy and the topical immunomodulator, imiquimod.

Non-Melanoma Skin Cancer

Non-melanoma skin cancer (NMSC) generally refers to the two most common cancers in the world: basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC). In 2003, there were an estimated 900,000-1,200,000 cases of NMSC (of which 75 to 80 percent were BCCs) in the United States, virtually equal in incidence to the 1,334,100 cases of all other cancers of all types combined. NMSCs account for about $650 million in annual medical care in the United States. The primary risk factors for NMSC include skin phenotype, which determines one's ability to tan, and age, which is a proxy for total ultraviolet exposure. Other risk factors include smoking, immunosuppressed state, outdoor work, and tanning bed use. Organ transplant patients have an increased risk of SCC due to their medical immunosuppression (Figure 4). SCC incidence correlates best with total, lifetime ultraviolet radiation exposure, whereas BCC occurrence corresponds better with intermittent sunlight exposure and severe sunburns. Rates of NMSC increase with decreasing latitude, and SCC doubles for each 8 to 10 degree decline. The case-fatality rate for BCC is less than 0.05 percent and for SCC it is less than 0.7 percent. These rates have been decreasing for the last 20 years. About 2,200 Americans die annually from NMSC, and the majority of these die of metastatic SCC. Metastatic BCC is incredibly rare. After developing an initial BCC or SCC, patients have about a 50 percent chance of developing another NMSC within five years. For Americans born in 1996, the lifetime risk of developing NMSC is about 20 percent. Appropriate sun protection, including hats, clothing, and regular sunscreen, are recommended for prevention of actinic keratoses and NMSC.

Superficial spreading BCC appears as a red, scaly, finely wrinkled plaque that may be confused with dermatitis (Figure 5 and Figure 6). The typical nodular BCC is a shiny or pearly, translucent papule with overlying telangiectases and rolled borders (Figure 7). Because the center often outgrows its blood supply, there might be a central, depressed ulcer with or without overlying hemorrhagic crust (Figure 8 and Figure 9). Infiltrative or morpheaform BCCs often feel indurated, resemble scars, and possess histologic margins far wider than would be suspected clinically (Figure 10). Microscopically, a basal cell carcinoma is characterized by islands of intensely basophilic keratinocytes with peripheral palisading seen extending from the bottom of the epidermis or freely as islands in the dermis. In the more infiltrative types of BCC, thin strands of atypical cells are found within scar-like collagen.

Squamous cell carcinomas are generally erythematous, scaly papules or plaques with ill-defined borders (Figures 11,

12, 13, and 14), and they might be confused with large, hypertrophic AKs. It often is difficult to differentiate these AKs from early SCCs without a biopsy. Microscopically, squamous cell carcinomas show a proliferation of pleomorphic keratinocytes confined to the epidermis (SCC in-situ) or extending into the dermis (invasive SCC).

Definitive diagnosis of NMSC requires a biopsy, and a shave, or tangential, biopsy is the preferred method. NMSCs might be treated with excision, electrodessication and curettage, liquid nitrogen, radiation, or topical imiquimod. Cure rate is 80 to 95 percent for BCCs or SCCs treated by these methods. Recurrent or large lesions, those located on high-risk areas or places where maximal normal tissue preservation is essential (such as the nose), and those with aggressive histologic patterns might be referred to a dermatologic surgeon for Mohs micrographic surgery. Mohs surgery achieves a 99 percent, five-year cure rate for primary tumors and a 95 percent cure rate for recurrent lesions. With this technique, thin layers of tissue are excised and tumors are mapped under microscopic control. Further layers are excised only from areas that have tumor remaining.

All patients with skin cancer and actinic keratoses should protect themselves from sun exposure by the appropriate use of hats, protective clothing, sunscreens, and avoidance of peak sunlight exposure. About 60 percent of cancer-causing ultraviolet rays reach the Earth's surface during a four-hour period centered on solar noon. The "shadow rule" is a simple guideline for patients to remember: Avoid direct sunlight when your shadow is shorter than you are.

References

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Figure Legends

Figure 1. Typical small, scaly, irregular papule of actinic keratosis on an ear lobe. (current figure 1)

Figure 2. Actinic keratosis on helical rim of an ear demonstrating ill-defined margins and hemorrhagic crust. (current figure 2)

Figure 3. Numerous scaly, erythematous AKs on a patient exposed to intense sunlight 50 years earlier in the Pacific Ocean during WWII.

Figure 4. Numerous ill-demarcated scaly papules on the dorsal hands and forearms of a renal transplant patient. The thicker lesions are clinically referred to as ‘verrucous keratoses'. Histologically, these lesions may be viral-induced verrucae (warts), hypertrophic actinic keratoses, or squamous cell carcinomas.

Figure 5. Typically eczematous appearing superficial BCC on the left dorsal forearm.

Figure 6. Numerous superficial BCCs of the chest.

Figure 7. Classic nodular basal cell carcinoma with necrotic center, pearly appearance, and telangiectasias just above eyebrow.

Figure 8. Ulcerated basal cell carcinoma on left cheek growing for 18 years!

Figure 9. 12 x 4 cm ulcerated BCC before and after (Figure 9b) Mohs micrographic surgery. Patient had been told three years earlier to have it excised, but she and a relative refused to believe it was a cancer and declined surgery.

Figure 10. Morpheaform BCC on the right cheek. These are clinically ill-demarcated, look like scars, and usually extend histologically more than 5 mm beyond the clinical margins. (Photo from AAD Slide Library.)

Figure 11. Squamous cell carcinoma-in-situ on the scalp. The atypical keratinocytes are confined to the epidermis.

Figure 12. Ill-demarcated and scaly plaque of squamous cell carcinoma in the triangular fossa of an ear.

Figure 13. Heaped-up squamous cell carcinoma on nasal bridge. Patient said that this had been growing for only four months. Squamous cell carcinoma typically grows more rapidly than basal cell carcinoma.

Figure 14. Another rapidly growing squamous cell carcinoma. Local lymph nodes were free of metastases.

Web sites

Skin Cancer Foundation: www.skincancer.org

Questions: Actinic Keratoses and Non-Melanoma Skin Cancer

1. A 58-year-old fair-skinned man presents with a 1cm diameter pearly papule with central hemorrhagic crust and peripheral telangiectasias. The most like diagnosis is:

A) melanoma
B) basal cell carcinoma
C) actinic keratosis
D) psoriasis

2. In evaluating the patient described in question 1, what diagnostic test should be performed?

A) KOH examination
B) Gram stain
C) Skin biopsy
D) Frozen section
E) Tzanck preparation

3. Appropriate treatment for actinic keratosis includes which of the following:

A) Liquid nitrogen
B) 5 - fluorouracil cream
C) Imiquimod
D) Photodynamic therapy
E) All of the above

Click here for answers.