Actinic Keratosis, Basal, and Squamous Cell Carcinoma



Actinic keratoses (AKs) are one of the most common skin findings in dermatology. AKs are benign neoplasms of the epidermis and are considered precursor lesions to nonmelanoma skin cancers. They are very common in sun-exposed areas of the skin, especially in the elderly patient. Ultraviolet light exposure is the main cause of AKs.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are the most common types of skin cancers and the most common cancers in the United States.1 Both are commonly seen in sun-exposed areas of the skin and are readily treatable if detected early. BCCs are the most common type of skin cancer and rarely metastasize. SCCs are the second most common skin cancer and can metastasize to regional lymph nodes if not treated early. Sun avoidance, use of proper clothing and sun screens, and routine examinations are important for prevention of nonmelanoma skin cancers.




Actinic keratoses (AKs) are precancerous lesions of the keratinocytes and are very common in the elderly Caucasian population. They typically occur on sun-exposed areas such as the head and neck areas, as well as the distal extremities. Ultraviolet (UV) light exposure is the most common cause of AKs, with a genetic predisposition also being important. An AK is a precursor lesion to SCC and should be treated with appropriate therapy.2


Actinic keratoses develop after intense or long-term exposure to UV light (natural or artificial). Chronic sun exposure may lead to p53 tumor suppressor gene mutation of individual keratinocytes in the epidermis.2 The same genetic mutations are seen in AKs and SCCs. The mutations will lead to propagation of the abnormal keratinocytes leading to faster division of these cells and development of a clinically visible lesion. If left untreated, approximately 10% of actinic keratosis may become SCCs.

Clinical Presentation


Patients typically complain of a scaly rough lesion(s) on frequently sun-exposed areas such as the face, scalp, and ears. Dorsal hands and forearms in men and lower legs in women are also commonly affected areas. The lesions usually do not have any symptoms such as itching or pain. Patients often try to scratch off the overlying crust, only to have the scaly surface reform.

Physical Examination

Actinic keratoses can present as a solitary lesion or as a larger, diffuse plaque. Solitary lesions often appear as an ill-defined, scaly, rough, red plaque that is approximately 3 to 6 mm in diameter. The lesions can be slightly sensitive to touch. Solitary AKs can also present as a more keratotic papule with a thicker stratum corneum above the base of the lesion (Figure 17-1). This type of a lesion can resemble a cutaneous horn and is frequently referred to as a hypertrophic actinic keratosis. The plaque-type AKs are very common in chronically sun-exposed areas such as the scalp in balding men. These lesions are very ill-defined and seemingly appear to involve a larger area. They are also scaly and rough feeling and can be associated with subclinical SCCs.

Figure 17-1.

Actinic keratoses. Hypertrophic and plaque-type actinic keratoses on scalp.

Laboratory Findings

Histopathology of AKs exhibits partial thickness atypia of the epidermis of the skin. The abnormal keratinocytes may also involve the appendageal structures of the skin such as hair follicles. These lesions are described histologically as “actinic keratoses with appendageal involvement” and may need more aggressive and deeper penetrating treatments to reach the involved appendages or follicular structures.


Actinic keratoses typically present as hyperkeratotic papules or as a scaly red plaque(s) in chronically sun-exposed areas of the face, scalp, ears, and dorsal hands and arms. They have a rough, gritty surface.

Differential Diagnosis

  • Seborrheic keratosis: Presents as tan or brown well-defined papule or plaque without a gritty surface.

  • Viral wart: Presents as a hyperkeratotic papule often with black dots representing thrombosed blood vessels.

  • SCC: Presents as a larger more indurated lesion.

A skin biopsy may be needed to differentiate these lesions if the clinical exam is not diagnostic.


There are many available options for treatment of actinic keratosis. These treatment modalities are often combined to offer the patients the most effective treatment options.

  • Cryotherapy (Chapter 7) is the most commonly used treatment for AKs.3 Liquid nitrogen is applied to the lesions using a spray dispenser or a cotton applicator until a 1- to 2-mm rim of frost develops around the actinic keratosis. This method may lead to blister formation in the lesions and surrounding skin. The blister heals and desquamates with resolution of the AKs.

  • Field therapy is used for more diffuse and numerous AKs. Several topical creams are available. 5-Fluorouracil (5-FU) (eg, Efudex, Carac) is a topical cream that has been available for decades and is commonly used for treatment of widespread lesions. 5-FU is a pyrimidine analog and incorporates into DNA and RNA of keratinocytes, leading to cell death and inflammation.4 Another common topical treatment is imiquimod (eg, Aldara) that works by stimulating T lymphocytes against the abnormal keratinocytes.3 In 2012 ingenol mebutate (Picato) was approved for actinic keratosis. This medication causes necrosis of AKs within 2 to 3 days of use.5 All topical field therapies caused intense inflammation in the treated sites (Figure 17-2).3

  • Photodynamic therapy (PDT) has gained greater popularity for treatment of AKs. In PDT, a chemical such as aminolevulinic acid is applied to the AKs and with exposure to light of the proper wavelength, the molecule is converted into protoporphyrin IX, a powerful photo-sensitizer, inside the abnormal keratinocyte. An energy-rich singlet oxygen species is generated causing membrane disruption and cell death.6

Figure 17-2.

Actinic keratoses after 4 weeks of treatment with 5-fluorouracil cream. Typical response to treatment with erythema, crust, and erosions in treated areas on the face.

If an AK does not resolve or recurs after treatment, a biopsy may be indicated to rule out an underlying SCC or BCC.

Sunscreen with SPF 30 or greater should be applied to all areas not covered by hats or clothing.

Indication for Consultation

Actinic keratosis that involve a large surface area or that do not respond to therapy should be referred to dermatology for field treatment options such as topical treatments and/or PDT.

Patient Information




Basal cell carcinoma (BCC) is by far the most common type of cancer and skin cancer in the United States. It is estimated that there are 1.2 to 1.5 million new cases each year in the United States with incidence rising annually.1 Fortunately, these are slow-growing, localized tumors with only rare metastatic potential. BCCs are more common in the elderly Caucasian population, but can be seen in the younger age group including patients in their twenties and thirties. Intense sun exposure or artificial UV light especially prior to age 18 is the primary cause of BCCs with family history and light-colored skin, hair, and eyes being important risk factors. Although less common, BCCs can appear in non-Caucasian patients.


Basal cell carcinomas are cancers of the epidermal keratinocytes of the hair follicles and the epidermis. They develop after intense or chronic UV light exposure. Ionizing radiation from therapeutic radiation therapy can also promote development of BCCs. Exposure to intense UV light leads to DNA mutation in the tumor suppressor genes of the sonic hedgehog pathway in keratinocytes. Mutations in the PTCH (patched) gene and in the tumor suppressor gene, p53 gene, are also important in the development of BCCs.2 Patients with basal cell nevus syndrome (Gorlin’s syndrome) develop hundreds of BCCs due to a genetic mutation in the sonic hedgehog pathway.

Clinical Presentation

History and Physical Examination

There are several types of BCCs, thus, the history and clinical presentations can vary depending upon the subtype. BCCs most commonly occur on frequently sun-exposed areas such as the head and neck.

  • Nodular basal cell carcinoma: Nodular BCC is the most common type subtype of BCCs. Patients often complain of a pimple-like lesion that does not heal or heals and then bleeds again. The lesions are often sore when touched or scratched. They typically appear as a translucent pearly papule with erythema, telangiectasia, and well-defined rolled borders most commonly on the head and neck region, especially the central face (Figure 17-3A and B). As the tumor grows, the center of the tumor often ulcerates creating a crater-like appearance. Thus, these lesions have been referred to as a “rodent ulcer” in the past. Occasionally, a nodular BCC can be pigmented giving an appearance of a melanoma or suspicious pigmented lesion (Figure 17-4).

  • Superficial basal cell carcinoma: This is the second most common subtype of BCC. Patients often complain of a chronic area of “eczema.” The lesions may be pruritic or sensitive to touch, but they typically do not bleed. These lesions appear as an erythematous patch or flat topped plaque with well-defined borders typically on the head and neck area, but also commonly appear on the trunk or extremities (Figure 17-5). They are often misdiagnosed and treated as eczema or psoriasis. Unlike nodular, superficial BCCs lack the translucent and telangiectatic appearance, but can have a slightly raised, rolled border.

  • Sclerotic/morpheaform basal cell carcinomas: This is the most aggressive subtype of BCC. Patients often complain of a chronic “scar” or the lesion goes unnoticed for years. Clinically, they appear as a scar-like plaque (Figure 17-6) that often lacks other features of nodular or superficial BCCs. Therefore, they can grow to be a large and deep tumor before clinical detection. Morpheaform BCCs can be slightly erythematous, but can also be lighter colored than the surrounding normal skin. The borders are very ill-defined making the diagnosis and treatment more difficult. They typically affect the head and neck region, but can appear anywhere on the body. Recurrent BCCs from a previously treated BCCs can often develop into sclerotic and morpheaform BCCs.

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Jan 15, 2019 | Posted by in Dermatology | Comments Off on Actinic Keratosis, Basal, and Squamous Cell Carcinoma
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