12: Common skin cancers

Abstract:

Concern for skin cancer is one of the most common reasons that patients seek out a skin examination. Approximately 20% of Americans develop skin cancer in their lifetimes, making this concern understandable. This chapter will review the three most common cutaneous malignancies: basal cell carcinoma, squamous cell carcinoma, and malignant melanoma.

Key terms:

basal cell carcinoma

squamous cell carcinoma

squamous cell carcinoma in situ

Bowen disease

melanoma

Chapter outline

Basal Cell Carcinoma
Squamous Cell Carcinoma
Malignant Melanoma

Basal cell carcinoma

Aziz Khan, Jonas Adalsteinsson, and Hao Feng

Clinical features

• Basal cell carcinoma (BCC) of the skin is the most common type of skin cancer. It is most common in Caucasians and uncommon in individuals with darker skin types. When darker-skinned patients develop a BCC, it is often pigmented clinically.
• The major risk factor for BCC development is ultraviolet (UV) exposure in the setting of predisposing genetics.
• BCCs develop in areas of chronic actinic skin damage, especially the face (70%) followed by the trunk (15%) and lower limbs of women.
• BCC has many variants, with the most common being the nodular, superficial, and morpheaform subtypes.

Nodular basal cell carcinoma

• Nodular BCC is the most common subtype, accounting for 80% of cases of BCC.
• It most commonly occurs on the face, especially the nose, cheeks, forehead, nasolabial folds, and eyelids.
• It typically presents as a pearly pink or flesh-colored papule or nodule with surface telangiectasias and often has a rolled raised border.
• It may enlarge and ulcerate (the so-called “rodent ulcer” appearance).
• Recurrent crusting or bleeding is often reported by the patient.

Superficial basal cell carcinoma

• Superficial BCC is the second most common subtype, accounting for 15% of cases.
• It most commonly occurs on the trunk.
• It typically presents as a light red to pink, slightly scaly, macule, patch, or thin papule or plaque that may appear shiny when illuminated.
• It is often asymptomatic and may appear nonspecific and subtle on examination.

Morpheaform basal cell carcinoma

• Morpheaform BCC accounts for 5% to 10% of cases.
• It typically presents as a smooth, white or flesh-colored papule or plaque with a depressed area of induration and irregular borders.
• It may resemble a scar.
• It is more aggressive than superficial or nodular BCC with a greater propensity for local destruction.

Other variants

• Other rare variants of BCC include infundibulocystic, basosquamous, metatypical, or fibroepithelioma of Pinkus (a rare variant of BCC that may be benign-appearing and present as a pink pedunculated lesion that can resemble an acrochordon).
• Both nodular and superficial BCCs can produce a variable amount of melanin; when pigmentation is noted, the lesion is often termed “pigmented BCC” and can clinically be confused with melanoma.

Work-up

• A detailed history should be obtained, focusing on the personal and family history of skin cancer; the use of immunosuppressive medication; and the existence of other underlying medical conditions, such as transplant history.
• Careful examination of the skin should be performed.
• After a lesion is identified as clinically suspicious, it is recommended that the lesion be evaluated using a dermatoscope (a handheld magnifier with a light source that can be polarized or nonpolarized with a transparent plate) to help you see deeper into the skin unobstructed by skin surface reflections.
• Dermoscopy assists with establishing the diagnosis of a BCC and is especially useful for distinguishing BCCs from intradermal nevi and sebaceous gland hyperplasia. It often helps to rub the lesion gently with alcohol because this will make the vessels more visible on dermoscopy.
• Dermoscopic features of BCC are mainly arborizing vessels, blue-gray ovoid nests, shiny white structures, leaf like structures, spoke-wheel areas, and the absence of findings typically associated with other skin conditions (such as the lack of a pigmented network, which is classically associated with melanocytic lesions).
• A full-body skin examination should be performed to identify concurrent BCCs or other types of skin cancers.
• Before removal, distant and close-up digital clinical photography should be undertaken to accurately portray the clinical location.
• In most cases, the suspected lesion should not be treated (using, for example, curettage or an electrodessication and curettage [ED&C]) before obtaining a skin biopsy. A skin biopsy is required to exclude less common mimickers (such as amelanotic melanoma) and establish the histologic subtype.
• Shave biopsies are, in most cases, sufficient to make an accurate diagnosis. Punch biopsies may be appropriate when the lesion is small and might have a deep extension. Incisional and excisional biopsies are rarely performed for diagnosing BCC.
• In areas where Mohs micrographic surgery (MMS) might be required, such as the face, only a small portion of the lesion is required to make the diagnosis. A biopsy with large margins might do the patient a disservice by removing an excessive amount of tissue.

Initial steps in management

• Treatment options for BCC include both surgical and nonsurgical therapies.
• Treatment selection depends on patient age, gender, comorbid conditions, and tumor characteristics.
• BCCs can generally be classified into low and high likelihood of recurrence after treatment. Tumor size, site, and histopathologic subtype determine the risk for recurrence.

• One risk feature is a tumor of any size on high-risk areas of the face (central face, nose, lips, eyelids, eyebrows, periorbital skin, chin, mandibles, ears, preauricular, postauricular areas, and temples), hands, or feet. The high-risk sites on the face include embryologic cleavage planes, which provide little resistance to tumor invasion.

• Tumors that are larger than 10 mm in diameter on the head and neck and larger than 20 mm in diameter in all other anatomic areas are also risks for recurrence.

• Aggressive pathologic features, such as the morpheaform, micronodular, and basosquamous subtypes, may also suggest a risk for recurrence.

• Other high recurrence risk features include recurrent lesions, tumors in sites of prior radiation therapy, tumors in patients on immunosuppressive therapy or with immunocompromised conditions, and tumors with perineural invasion.
• Primary goals of therapy include complete removal of the tumor to prevent recurrence and the provision of an optimal cosmetic outcome.

Surgical treatment options

Surgical treatment options include standard surgical excision, ED&C, and MMS.

• Standard surgical excision is the first-line therapy for tumors with a low risk for recurrence in suitable anatomic locations, such as the trunk and extremities.

• Standard surgical excision may also be an alternative treatment option for select high-risk patients when MMS is not available or not preferred by the patient.

• For low-risk patients, margins of 3 to 4 mm are considered to be appropriate. For high-risk patients, margins greater than 4 mm are more appropriate.
• ED&C is an option for small, low-risk BCCs on the trunk and extremities.

• Its main advantages include that it is less invasive than wide excision and more convenient for many patients.

• Disadvantages include a higher recurrence rates (inability to confirm clearance histologically) and a poor cosmetic outcome because a scar will result. Thus it is often used mainly for BCCs on the trunk and extremities.
• MMS provides the best long-term cure rates and a superior cosmetic outcome.

• It is the first-line therapy for high-risk BCCs and recurrent BCCs on cosmetically and functionally sensitive areas.

• Examination of all tissue margins during the procedure allows for the identification of inapparent subclinical tumor extension, resulting in excellent long-term cure rates.

• It maximizes tissue sparing, thus allowing the preservation of vital structures and providing the best cosmetic outcome.

• Disadvantages include cost (although it is cost effective for appropriate lesions), lack of availability in many counties in America, and the lengthy procedure time (typically 2–4 hours).

Nonsurgical treatment options

Nonsurgical treatment options include cryosurgery, topical therapies, and radiation therapy.

• Cryosurgery is a relatively quick, cost-effective procedure, which is in some cases indicated for smaller, superficial BCCs of the trunk for those wishing to avoid surgical procedures.

• Liquid nitrogen is used to freeze the tumor and a small surrounding margin of normal-appearing skin.

• Disadvantages of cryotherapy include a higher recurrence rate and poor cosmetic outcome (can cause hypertrophic scarring and permanent hypopigmentation).
• Topical therapies for BBC include 5-fluorouracil (5-FU) 5% cream and imiquimod 5% cream. Both are approved by the U.S. Food and Drug Administration (FDA) for the treatment of superficial BCCs.

• Topical therapies are indicated for patients with multiple superficial BCCs, those who are poor surgical candidates, and those who do not wish to undergo surgery. It should not be done on tumors with high-risk features and cosmetically and functionally sensitive areas.

• 5-FU 5% cream is generally applied twice daily for 4 to 6 weeks; however, some patients may achieve the desired inflammatory response (erythema, crusting, and scab formation) in as early as 2 weeks.

• Imiquimod 5% cream is applied at bedtime 5 days per week for 6 weeks until the target inflammatory reaction is achieved. Imiquimod can be bothersome for patients to use because it comes in single-use packets. Each packet of cream, however, may be enough for multiple uses by the patient and therefore needs to be left open after each use. We recommend slicing a small opening in the packet from which the patient can squeeze a small amount of medicine daily.

• Major disadvantages of topical therapy include application site reactions, hypopigmentation or hyperpigmentation, inability to confirm complete clearance of tumor histologically, and a higher recurrence rate. Some patients also complain of flu like symptoms if the topical creams are applied to a larger area.
• Radiation therapy is an alternative option when surgery is contraindicated.

• It can also be used as an adjuvant treatment of BCC when complete tumor removal is not achievable because of invasion of vital structures by tumor cells.

• Disadvantages of radiation therapy include its high recurrence rate, high cost, prolonged course of therapy, poor cosmetic outcome, and increased risk for future skin cancers.
• Other nonsurgical treatment options for BCC include photodynamic therapy (which is a noninvasive, nonscarring treatment for superficial BCCs), systemic therapy with vismodegib or sonidegib (which are sonic hedgehog pathway blockers that are approved by the FDA for the treatment of advanced or metastatic BCC), and 500 mg of nicotinamide twice daily to decrease the incidence of nonmelanoma skin cancers.

TABLE 12.1

Summary of Commonly Encountered Clinical Scenarios Involving Basal Cell Carcinomas

Clinical Scenario	Treatment Recommendations
BCC of the trunk or extremities, with positive margins after biopsy	• A standard excision with 4-mm clinical margins provides the highest chance of a cure. • ED&C if patient would prefer to avoid surgery and stitches. There is a higher risk for recurrence and the patient must be counseled on the scar that will result. • Topical imiquimod or 5-FU for small/superficial lesions if the patient wants to avoid surgical intervention. Close clinical follow-up is recommended.
BCC of the trunk or extremities with negative margins after biopsy Note: negative margins on biopsy may not reflect true clinical negative margin	• Do nothing and clinically follow the patient. • A standard excision or ED&C. • Imiquimod or 5-FU for 3–6 weeks; chance of recurrence is still 10%–20%.
BCC of the trunk or extremities, less than 20 mm diameter: positive margins after standard excision	• Standard re-excision. • Consider an MMS referral.
BCC of a cosmetically or functionally critical area on the face/neck/hands/feet with positive margins	• MMS
BCC of a cosmetically critical area on the face/neck with negative margins Note: negative margins on biopsy may not reflect true clinical negative margin	• Strongly consider MMS referral to minimize chance of recurrence and optimize cosmetic outcome. • Watch with a close clinical follow-up. • Imiquimod or 5-FU for 3–6 weeks; chance of recurrence is still 10%–20%.
Multiple BCCs	• Topical therapy using 5-FU or Imiquimod. • Photodynamic therapy. • Sonic hedgehog pathway inhibitors for extreme cases, such as Gorlin syndrome. Often not tolerated because of side effects.

BCC, Basal cell carcinoma; ED&C, electrodessication and curettage; MMS, Mohs micrographic surgery; 5FU, 5-fluorouracil.

Warning signs/common pitfalls

• After a first diagnosis of BCC, patients should be referred to a dermatologist because there is an increased risk for developing additional or recurrent BCCs as well as other cancerous or precancerous skin conditions.
• Pigmented BCCs should be distinguished from melanoma because therapy and prognosis differ significantly for both conditions.
• The differential for BCCs includes Merkel cell carcinoma and amelanotic melanoma, tumors which both have high metastatic potential. Therefore biopsy is strongly recommended in most cases to confirm the diagnosis. A Merkel cell carcinoma or amelanotic melanoma treated with ED&C without a biopsy could have disastrous consequences. BCCs, especially superficial BCCs, can also be confused with inflammatory skin conditions, like nummular dermatitis or psoriasis. The possibility of a superficial BCC should be considered if a presumed inflammatory lesion does not respond to topical steroids.
• If a biopsy is undertaken and margins are clear, there is still a 20% to 30% risk for tumor recurrence as negative margins on biopsy may not reflect true clinical negative margin. Topical therapy with imiquimod or 5-FU can be used to reduce recurrence risk, or standard surgical treatment can be performed to ensure full clearance. For areas of high cosmetic importance, MMS should be strongly considered despite biopsy margins being negative.

Counseling

Skin cancers occur when healthy skin cells transform into abnormal cells. Basal cell carcinoma is a common type of skin cancer and the least dangerous type of skin cancer. Basal cell carcinoma can be, in most cases, entirely removed when caught early. Very rarely, it spreads to other parts of the body; however, it can spread locally if left untreated.

Skin cancer can present as a nonspecific abnormal area of skin. It can present as a pink, crusty, bleeding bump or as a wound that will not heal. You should always show your doctor any skin changes you think might be abnormal. Your doctor will examine the spots and check the skin all over your body. Further tests, including a skin biopsy, will be suggested if your doctor suspects a skin cancer.

Skin cancer is often caused by chronic sun exposure. Sun exposure is the most important and most preventable risk factor for all skin cancers, including basal cell carcinoma. Damaging effects of sun are cumulative and therefore sun protection is urged, no matter what your age is.

You can prevent skin cancers by helping protect your skin from sun damage. Apply sunscreen to all exposed areas, preferably a water-resistant sunscreen with a Sun Protection Factor (SPF) of at least 30 that provides broad-spectrum protection from both ultraviolet A (UVA) and ultraviolet B (UVB) rays. Reapply every 2 hours, even on cloudy days, and after sweating or swimming. Sunscreens are not perfect because some ultraviolet light may still get through; do not use them to allow you to prolong your sun exposure. You should seek shade when possible and be aware that the sun’s rays are the strongest between 10 AM and 4 PM. Wear sun-protective clothing, such as pants, a wide-brimmed hat, a long-sleeved shirt, and sunglasses, when possible. Some sunlight will still get across your clothing. You can wear sunscreen underneath, or you can buy clothing that has been treated to give additional sun protection.

Protect children from sun exposure by dressing them in protective clothing, applying sunscreen after they are older than 6 months, and having them play in the shade. Use extra precaution when near water, snow, and sand. These surfaces reflect the damaging rays of the sun and can increase your chance of getting sunburnt. Get vitamin D safely through a healthy diet rather than seeking the sun for vitamin D.

Avoid tanning beds. UV rays from tanning beds can also lead to wrinkling and skin cancer. Perform a regular self-skin examination. If you notice anything changing, growing, or bleeding on your skin, see a dermatologist. Skin cancer is very treatable when caught early.

Squamous cell carcinoma

Aziz Khan, Jonas Adalsteinsson, and Hao Feng

Clinical features

Cutaneous squamous cell carcinoma (SCC) is the second most common type of skin cancer in the United States.

• Incidence increases with age; it is uncommon in those under 45 years of age and it is more common in Caucasians.
• The major risk factor for SCC development is UV exposure in the setting of predisposing genetics, immunosuppression and/or HPV (human papilloma virus)
• SCCs can develop on any cutaneous surface. SCCs most commonly arise on sun-exposed areas in Caucasians and non–sun-exposed areas in individuals with darker skin types.
• They can clinically present with so-called “horns” with thick, vertically oriented hyperkeratotic scale. This type of lesion should always be biopsied to sample the base of the lesion.