Diagnosis and Treatment of Malignant and Premalignant Lesions

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34 Diagnosis and Treatment of Malignant and Premalignant Lesions

Daniel L. Stulberg, MD, and Richard P. Usatine, MD

Skin cancer is the most common cancer in the United States; fortunately, however, it is not one of the most common causes of death. Skin cancers are usually divided into melanoma and nonmelanoma skin cancers. An approximate breakdown of the most common skin cancers in the United States indicates that 80% are basal cell carcinomas (BCC), 16% squamous cell carcinomas (SCC), and 4% melanomas. Some of the rare skin cancers include Merkel cell carcinoma, dermatofibrosarcoma protuberans, and cutaneous T-cell lymphoma. These account for less than 1% of skin cancers.

Nonmelanoma skin cancer typically refers to BCC and SCC. Cutaneous metastases (of nonskin cancers), human papilloma virus–related cancers, tumors arising from dermal fibroblasts, neuroendocrine cells, and cutaneous lymphomas also occur. Both BCC and SCC have an increased incidence in people with fair skin, with increased sun exposure, and with aging. Patients with xeroderma pigmentosum have a very high rate of skin cancers due to sun exposure and UVB damage because they are unable to correct errors in their sun-damaged skin, leading to multiple skin cancers. SCCs are also more frequent in skin that is exposed to carcinogens or affected by chronic wounds or burns. BCCs very rarely metastasize, but can cause severe complications and even death from local invasion if left untreated. SCCs can metastasize although this is not common in skin lesions that are not on mucosal surfaces.

For melanoma, risk factors include family history, large congenital nevi, the familial atypical mole and melanoma syndrome (FAMMS; previously dysplastic nevus syndrome) (Figure 34-1) and sun exposure, particularly blistering burns in fair-skinned individuals. After initial biopsy, Breslow’s classification by depth of invasion is used to guide re-excision margins and the need for sentinel lymph node biopsy and to predict general survival rates.

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FIGURE 34-1 Young man with familial atypical mole and melanoma syndrome (FAMMS; previously called dysplastic nevus syndrome).

(Copyright Daniel L. Stulberg, MD.)

In dealing with suspected skin cancer, the usual first step is to biopsy the lesion to confirm the diagnosis. For suspected melanoma, it is preferable to remove the lesion in its entirety with the initial biopsy if possible unless precluded by the size or location of the lesion. A deep shave (scoop shave) to diagnose melanoma can be done if the biopsy is deep enough to get under the entire lesion. Two or more 4- to 6-mm punch biopsies can often determine the diagnosis if the lesion is large and the clinician is not skilled at doing a deep shave. The risk of sampling error is greater with punch biopsies so a negative result may be a false negative. In SCCs and BCCs a shave biopsy is usually the easiest and least invasive way to get tissue to confirm the diagnosis. Having a histologic diagnosis can prevent a large unnecessary excision if the pathology turns out to be benign and can help guide the treatment of choice if malignancy is confirmed.

Actinic Keratoses, Actinic Cheilitis, and Bowen’s Disease

Actinic keratoses (AK), actinic cheilitis, and Bowen’s disease (SCC in situ) are all caused by cumulative sun exposure and have the potential to become invasive squamous cell carcinomas. The rate of malignant transformation has been variably estimated but is probably no greater than 6% per AK over a 10-year period.1 On a spectrum of malignant transformation, Bowen’s disease is squamous cell carcinoma in situ before the squamous cell carcinoma becomes invasive. In one large prospective trial, the risk of progression of AK to primary SCC (invasive or in situ) was 0.6% at 1 year and 2.6% at 4 years. Approximately 65% of all primary SCCs and 36% of all primary BCCs diagnosed in the study group arose in lesions that had been previously diagnosed clinically as AKs.2

Actinic keratoses are rough scaly spots seen on sun-exposed areas that may be found by touch, as well as close visual inspection. Bowen’s disease appears similar to actinic keratosis, but tends to be larger in size and thicker with a well-demarcated border (Figure 34-2). Actinic cheilitis is equivalent to AK but found on the lips (Figure 34-3).

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FIGURE 34-2 Bowen’s disease (SCC in situ) on the leg.

(Copyright Richard P. Usatine, MD.)

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FIGURE 34-3 Actinic cheilitis undergoing cryosurgery.

(Copyright Richard P. Usatine, MD.)

Typical distribution of AKs and SCC in situ are the areas with greatest sun exposure such as the face, forearms, dorsum of hands, upper chest, lower legs of women, and the balding scalp and tops of the ears in men. Actinic keratoses that appear premalignant may be diagnosed by history and physical exam only and treated with destructive methods without biopsy. Bowen’s disease requires a biopsy for diagnosis. Bowen’s disease or squamous cell carcinoma should be biopsied prior to treatment. A shave biopsy should usually produce enough tissue for histopathology.

Treatment of Actinic Keratoses and Actinic Cheilitis

Cryotherapy

• Light freeze, 1-mm freeze margin.
• Treating AKs with liquid nitrogen using a 1-mm halo freeze demonstrated complete response of 39% for freeze times of less than 5 seconds, 69% for freeze times greater than 5 seconds, and 83% for freeze times greater than 20 seconds.3
• Considerably more hypopigmentation is caused by 20 seconds of freeze time, so base the freeze time on the size, location, and thickness of the AK.
• Excellent for a small number of lesions.
• Adjunct before and after topical therapies.

 

Electrodesiccation and Curettage (Single Cycle for AK)

• Use local anesthetic.
• Useful for thicker lesions (see pages 177–178).
• Adjunct after topical therapies.

 

Photodynamic Therapy

• Requires special equipment (see Chapter 27, Photorejuvenation with Lasers).

Topical Medications

Topical medications are useful for a large area or large number of lesions in a region.

Fluorouracil

• 5% cream (Efudex), 1% cream (Fluoroplex), 0.5% microspore cream (Carac).
• Apply twice daily for 2 to 4 weeks. Usually need 4 weeks for the arms and the back of the hands. Patients should stop if the skin becomes ulcerated or infected.
• Causes marked inflammation (Figure 34-4).
• 0.5% microspore cream (Carac) may cause less inflammation.
• Treat remaining lesions with cryotherapy or curettage and electrodesiccation.

 

Imiquimod 5% (Aldara)

• Apply QHS 3 to 4 times per week up to 16 weeks.
• Long treatment period.
• Not as effective as fluorouracil.

 

Diclofenac Gel 3% (Solaraze)

• Apply twice daily for 90 days.
• Long treatment period.
• Not as effective as fluorouracil.
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FIGURE 34-4 (A) Erythema and scaling secondary to 5-FU use to treat multiple actinic keratoses on the face. (B) The skin is much improved after the erythema resolves.

(Copyright Richard P. Usatine, MD.)

Treatment of Bowen’s Disease

The following is based on the guidelines from Cox et al.4:

• The risk of progression to invasive cancer is about 3%. This risk is greater in genital Bowen’s disease (BD), and particularly in perianal BD. A high risk of recurrence, including late recurrence, is a particular feature of perianal BD, and prolonged follow-up is recommended for this variant.
• There is reasonable evidence to support use of 5-fluorouracil (5-FU).4 It is more practical than surgery for large lesions, especially at potentially poor healing sites, and has been used for “control” rather than cure in some patients with multiple lesions.
• Topical imiquimod is likely to be used for BD especially for larger lesions or difficult/poor healing sites. However, it is costly and the optimum regimen has yet to be determined.5
• One prospective study suggests that a curettage and electrodesiccation treatment is superior to cryotherapy in treating BD, especially for lesions on the lower leg.6 Curettage was associated with a significantly shorter healing time, less pain, fewer complications, and a lower recurrence rate when compared with cryotherapy.6
• Cryotherapy has good evidence of efficacy but discomfort and time to healing are inferior to photodynamic therapy (PDT) or curettage. With discretion, SCC in situ can be treated by cryotherapy with liquid nitrogen spray by a 30-second freeze, thaw and refreeze 30 seconds (see Chapter 15, Cryosurgery).
• Photodynamic therapy has been shown to be equivalent to cryotherapy and 5-FU, either in efficacy and/or in healing.4 PDT may be of particular benefit for lesions that are large, on the lower leg, or at otherwise difficult sites, but it is costly.
• Excision should be an effective treatment with low recurrence rates, but the evidence base is limited and for the most part does not allow comment on specific sites of lesions. Lower leg excision may be limited by lack of skin mobility. Although elliptical excision with clear margins is an effective and acceptable treatment for Bowen’s disease, it is too aggressive for actinic keratoses.
• Mohs surgery is recommended for BD at sites such as the digits or penis where it is important to limit removal of unaffected skin (Figure 34-5). It is useful for poorly defined or recurrent head and neck BD.
• See Table 34-1 for a summary of all recommended treatments for Bowen’s disease based on location and other characteristics.
image

FIGURE 34-5 Bowen’s disease on the finger secondary to human papilloma virus. Evidence for HPV was seen in the biopsy specimen performed with a shave.

(Copyright Richard P. Usatine, MD.)

TABLE 34-1 Summary of the Main Treatment Options for Bowen’s Disease4

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Special Considerations/Billing

• AK and actinic cheilitis treatment are coded as premalignant.
• 17000 for first lesion treated.
• 17003 repeated for each lesion 2–14.
• 17004 stand-alone code if more than 15 lesions treated.
• Treatment of Bowen’s disease is coded the same as SCC (see below).

Basal Cell Carcinoma

Diagnoses

• Frequent on the face, hands, upper chest, and sun-exposed skin.
• Nodular is the most common form (Figure 34-6):

• Raised, waxy, translucent, or pearly border.
• Central erosion, telangiectasias, and bleeding are common.
• Usually flesh colored or pale, but may be pigmented, confusing it with melanoma.
• Superficial BCC (Figure 34-7)

• Flat or slightly raised, often red to brown.
• Look for a thready border that may be pearly.
• More often on the trunk and arms than face.
• Morpheaform (also called sclerosing) (Figure 34-8)

• Usually has nondiscrete margins.
• More aggressively infiltrating.
• Higher recurrence rate.
• Shave biopsy can confirm diagnosis.
image

FIGURE 34-6 Typical nodular BCC on the face of a 53-year-old man. Note the pearly borders and telangiectasias.

(Copyright Richard P. Usatine, MD.)

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FIGURE 34-7 Superficial BCC on the back with erythema, scale, and a thready border.

(Copyright Richard P. Usatine, MD.)

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FIGURE 34-8 Sclerosing BCC that turned out to be widely invasive when removed with Mohs surgery.

(Courtesy of Ryan O’Quinn, MD.)

Removal

(See Table 34-2 for cure rates of BCC treatment modalities.)

Elliptical Excision (Fusiform) (Figure 34-9)

• Remove with 3-mm surgical margin if discrete border and clinically feasible, 4 to 5 mm if indiscrete border.7
• Consider using a skin curette to define the margins of the BCC and redraw the ellipse as needed (Figure 34-10).
• Heals with linear scars, which can be hidden in skin lines.
• Provides immediate closure.
• Provides tissue for pathology and assurance of removal.
• If you find evidence of the BCC at the base or edges (Figure 34-11) of the removed specimen, take another piece of skin or fascia at a deeper and/or wider level and put it in a second formalin container with a stitch used to mark its orientation in the body.

 

Electrodesiccation and Curettage

• BCC tissue is softer than the surrounding normal tissue so a skin curette can remove the BCC without taking too much normal tissue around it (Figure 34-12).
• Firmly curette in all directions then electrodesiccate and repeat to a total of three cycles at one visit (see Chapter 14, Electrosurgery, pages 177–178).
• Useful for smaller lesions or where closure of a full-thickness excision would be difficult.

 

Mohs Micrographic Surgery (Figure 34-13)

• The most effective in achieving cure with clean margins—99%.
• Specialized skin surgeon examines pathology at time of excision.
• Further resection as needed at time of surgery.
• Can minimize impact on adjacent structures.
• Useful for uncertain borders or aggressive forms of BCC (i.e., sclerosing or morpheaform).7
• Consider for H-zone on face (See Figure 37-12 on page 461), especially for recurrent BCC.8
• Consider referral for Mohs micrographic surgery if lesions affect sensitive structures including the eyelids, ala of the nose, and the ear canal.
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