• 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.

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 Disease ⁴

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.

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.)

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

(Copyright Richard P. Usatine, MD.)

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.

• Consider referral for Mohs if aggressive lesion or if recurrent lesion.

• Basosquamous carcinoma is an aggressive subtype of basal cell cancer that has metastatic potential and high recurrence rates that should be managed by Mohs surgery.

Topical Immunotherapy

• Imiquimod (Aldara) locally boosts immune response.

• FDA approved for superficial BCC (not for other subtypes) lesions up to 2 cm in diameter. Not approved for use on the face, hands, or feet. (Note that many BCCs are on the face and hands.)

Cryotherapy

• With discretion, superficial BCC can be treated by cryotherapy with liquid nitrogen spray by a 30- to 45-second freeze (thaw and refreeze 30 to 45 seconds) (Figure 34-14) (see Chapter 15).

Radiation Therapy

• Usually reserved for those not able to tolerate other treatments.

Photodynamic Therapy (PDT)

• PDT has a number of limitations in the treatment of BCC.⁹

TABLE 34-2 Cure Rates for Different Skin Cancer Treatment Modalities

	Five-Year Cure Rate (%)
	BCC	SCC
Surgical excision	89.9	91.9
Cryotherapy	92.5	NA
Electrodesiccation and curettage	92.3	96.3
Radiotherapy	91.3	90.0
Mohs surgery	99.0	96.9

NA, not applicable.

Source: Data from Rowe DE, Carroll RJ, Day CL. J Dermatol Surg Oncol. 1989;15:315–328, and J Am Acad Dermatol. 1992;26:976–990; and Vidimos A, Ammirati C, Poblete-Lopez C. Dermatologic Surgery. London: Saunders; 2008, Table 16-1.

FIGURE 34-9 (A) Ellipse marked around a nodular BCC on the neck with a 3 : 1 length : height ratio. (B) After 1 month the scar is becoming invisible as it matches the natural skin lines of the neck.

(Copyright Richard P. Usatine, MD.)

FIGURE 34-10 After marking the margins and anesthetizing the area, a curette is being used to determine the full margins of the BCC more accurately. An adjusted ellipse can then be drawn to avoid incomplete excision.

(Copyright Richard P. Usatine, MD.)

FIGURE 34-11 Basal cell carcinoma palpable and barely visible (whiter than the yellow fat) at the base of this elliptical excision. A second layer should be removed more deeply before closing up the surgical defect.

(Copyright Richard P. Usatine, MD.)

FIGURE 34-12 A curette is scooping out the abnormally soft cancer tissue from this basal cell carcinoma on the arm as the first step of an electrodesiccation and curettage.

(Copyright Richard P. Usatine, MD.)

FIGURE 34-13 Mohs surgery being performed of a basal cell carcinoma of the upper lip region. First the tumor was debulked and now a thin sliver of tissue is being removed 360 degrees around the original tumor to look for adequate margin control.

(Courtesy of Ryan O’Quinn, MD.)

FIGURE 34-14 Cryosurgery being performed on a superficial BCC of the arm. A 5-mm margin of freeze is the goal with two freezes each of 30 seconds duration.

(Copyright Richard P. Usatine, MD.)

Special Considerations/Billing

• High risk of additional and future BCC and SCC, so frequent reexamination for additional lesions is required at least annually.¹⁰

• CPT codes for destruction or excision of malignancy should be used.

Squamous Cell Carcinoma

Diagnoses

• Erythematous plaque with scale and/or ulceration, frequently found on the face, ears, and lower lip (Figure 34-15). May occur in any sun-exposed area or on mucous membranes of the mouth and anus.

• Transplant patients on chronic immunosuppression are at high risk to develop SCC (Figure 34-16).

• May be at the base of actinic horns or thick actinic keratoses.

• May occur in areas of chronic irritation or burns.

• A shave or punch biopsy is useful for diagnosis.

FIGURE 34-15 Squamous cell carcinoma of the lower lip related to sun exposure.

(Copyright Richard P. Usatine, MD.)

FIGURE 34-16 Large quickly growing SCC on the lip of a patient on immunosuppression after a renal transplant.

(Copyright Richard P. Usatine, MD.)

Special Considerations/Billing

• Consider referral for Mohs micrographic surgery if lesions affect sensitive structures including the eyelids, ala of the nose, and the ear canal.¹¹

• Consider referral for Mohs if aggressive lesion or if recurrent lesion.

• High risk of additional and future BCC and SCC so frequent reexamination for additional lesions is required at least annually.¹⁰

• See Table 38-3 for ICD-9 coding and CPT coding that is specific to the procedure used to treat the malignancy.

Keratoacanthoma

Most pathologists and skin experts consider KA to be one type of SCC. The controversy revolves around the fact that it was considered a precancer for years, in part, because some KAs will spontaneously resolve.

Removal

• Electrodesiccation and curettage (see pages 177–178).

• Excision by ellipse with 3 to 5 mm margins.

• Inject 5-FU, methotrexate, or interferon.

• Radiation therapy if unable to treat by measures above.

Billing

• Bill using CPT codes for destruction or excision of malignant lesions.

Melanoma

Diagnosis

• Use the ABCDE guidelines for diagnosing melanoma (Figure 34-18).

• A = Asymmetry. Most melanomas are asymmetrical: a line through the middle will not create matching halves.

• B = Border. The borders of melanomas are often uneven and may have scalloped or notched edges.

• C = variation in Color. Melanomas are often varied shades of brown, tan, or black. As melanomas progress, they may appear red, white, and blue.

• D = Diameter greater than or equal to 6 mm. Melanomas tend to grow larger than most nevi. (Note: Congenital nevi are often large.)

• E = Evolving or Elevated. Any enlarging nevus is suspect for melanoma even though benign nevi may also grow. Melanoma is often elevated, at least in part, so that it is palpable.

• A prospective controlled study compared 460 cases of melanoma with 680 cases of benign pigmented tumors and found significant differences for all individual ABCDE criteria (p < 0.001) between melanomas and benign nevi.¹²

• Sensitivity of each criteria (percentage of melanomas that were positive for each one of the ABCDE criteria): A, 57%; B, 57%; C, 65%; D, 90%; E, 84%.¹²

• Specificity of each criteria (percentage of benign nevi that were negative for each one of the ABCDE): A, 72%; B, 71%; C, 59%; D, 63%; E, 90%.¹²

• Sensitivity of ABCDE criteria varies depending on the number of criteria needed: Using two criteria, the sensitivity was 89.3; with three criteria, 65.5% (i.e., 34.5% did not have at least three criteria positive so melanomas should not be expected to meet all criteria).

• Specificity was 65.3% using two criteria and 81% using three.¹²

• The number of criteria present was different between benign nevi (1.24 ± 1.26) and melanomas (3.53 ± 1.53; p < 0.001). No significant difference was found between melanomas and atypical nevi.¹²

Clinical Appearance

• The “ugly duckling” rule: If a mole looks different than the patient’s other moles, there is a higher likelihood that it is malignant (Figure 34-19).

• May be friable, ulcerating, nonhealing, or bleeding.

FIGURE 34-18 Superficial spreading melanoma with all features of ABCDE.

(Courtesy of Skin Cancer Foundation, New York, NY.)

FIGURE 34-19 The “ugly duckling” sign with one pigmented lesion standing out on the upper right side of the back. This was indeed a malignant melanoma caught early by careful observation.

(Copyright Richard P. Usatine, MD.)

The four major categories of melanomas are as follows:

1. Superficial spreading melanoma is the most common type of melanoma, accounting for about 70% of melanomas in the United States.¹³ This melanoma has a radial growth pattern before dermal invasion occurs (Figure 34-20). The first sign is the appearance of a flat macule or slightly raised discolored plaque that has irregular borders and is somewhat geometrical in form. The color varies with areas of tan, brown, black, red, blue, or white. These lesions can arise in an older nevus. The melanoma can be seen almost anywhere on the body, but is most likely to occur on the trunk in men, the legs in women, and the upper back in both. Most melanomas found in the young are of the superficial spreading type.

2. Nodular melanoma occurs in 15% of melanoma cases.^13,¹⁴ The color is most often black, but occasionally is blue, gray, white, brown, tan, red, or nonpigmented (Figure 34-21). It is often ulcerated and bleeding at the time of diagnosis. The nodule in Figure 34-21 is multicolored. Although it is often evolving and elevated, it may lack the ABCD criteria.

3. Lentigo maligna melanoma (LMM) is found most often in the elderly and arises on the chronically sun-damaged skin of the face. The term lentigo maligna is used for the melanoma precursor in the setting of atypical melanocytic hyperplasia alone and the term melanoma in situ, LM type, is used to represent the true in situ melanoma. LM is the precursor to LMM and not a nevus (Figure 34-22). Globally, LM/LMM is estimated to account for 4% to 15% of all melanomas, and 10% to 26% of all head and neck melanomas.¹⁵

4. Acral lentiginous melanoma is the least common subtype of melanoma and accounts for 2% to 3% of melanomas.¹³ It occurs under the nail plate or on the soles or palms (Figure 34-23). Acral lentiginous melanoma has 5- and 10-year melanoma-specific survival rates of 80.3% and 67.5%, respectively, which is less than those for all cutaneous malignant melanomas overall (91.3% and 87.5%, respectively; p < 0.001).¹³ Subungual melanoma may manifest as diffuse nail discoloration or a longitudinal pigmented band within the nail plate. When subungual pigment spreads to the proximal or lateral nail fold, it is referred to as Hutchinson’s sign and is highly suggestive of acral lentiginous melanoma (Figure 34-24).

FIGURE 34-20 Superficial spreading melanoma in its radial growth phase on the back of the patient above (0.35 mm in depth).

(Copyright Richard P. Usatine, MD.)

FIGURE 34-21 Nodular melanoma on the shoulder of a young woman. After being missed by a previous doctor, the nodular melanoma was excised with an elliptical excision and found to be 8.5 mm in depth.

(Copyright Richard P. Usatine, MD.)

FIGURE 34-22 Lentigo maligna melanoma on the face.

(Courtesy of Skin Cancer Foundation, New York, NY.)

FIGURE 34-23 Acral lentiginous melanoma on the heel of a young woman.

(Copyright Richard P. Usatine, MD.)

FIGURE 34-24 Subungual melanoma that has spread to the proximal nail fold producing a positive Hutchinson sign.

(Courtesy of Ryan O’Quinn, MD.)

Less common types of melanomas include the following:

• Amelanotic melanoma (<5% of melanomas) is nonpigmented and appears pink or flesh colored, often mimicking BCC or SCC or a ruptured hair follicle. It may be a nodular melanoma subtype or melanoma metastasis to the skin, because of the inability of these poorly differentiated cancer cells to synthesize melanin pigment (Figure 34-25).

• Other rare melanoma variants include (1) desmoplastic/neurotropic melanoma, (2) mucosal (lentiginous) melanoma, (3) malignant blue nevus, and (4) melanoma arising in a giant congenital nevus.

FIGURE 34-25 Amelanotic melanoma arising on the scalp.

(Courtesy of the University of Texas Health Science Center San Antonio, Division of Dermatology, San Antonio, TX.)

Diagnosis starts with history (change) and physical exam (ABCDE).

• Use dermoscopy if available (see Chapter 32, Dermoscopy).

• Biopsy per recommendations in Chapter 8, Choosing the Biopsy Type.

• It is better to give the pathologist the whole lesion or a large representative portion of the lesion rather than a few small punch biopsies.

• A broad deep shave is often better than a single punch biopsy unless the punch biopsy will remove the whole lesion.

Treatment

Definitive treatment is based on Breslow depth.

• Surgical excision is based on the recommendations given in Table 34-3.

• If depth greater than 1.0 cm, refer to surgical oncologist for excision and simultaneous sentinel node biopsy.

• When dealing with facial, acral, or anogenital melanomas, Mohs surgery may be preferable to allow reduced margins and conservation of tissue.^16,¹⁷

• Staging of the melanoma is accomplished using the TNM system.

TABLE 34-3 Recommended Excision Margins for Melanoma ^a

Tumor Thickness (Breslow)	Excision Margin (cm)	Sentinel Node Biopsy Suggested
In situ	0.5	No
<1.0 mm	1	No
1.0–2.0 mm	1	Yes
>2.0 mm	2	Yes

^a These recommendations are based on both prospective, randomized studies and international consensus conferences.^16,¹⁷ Limited data suggest that margin has an effect on local or regional recurrence, but there are no data to support an impact of margin on survival.^16,¹⁷

Oncology referral is based on staging (including if sentinel node positive or >4 mm in depth). Close clinical follow-up—at least annual complete skin examinations—is required.

Cutaneous T-Cell Lymphomas (Including Mycosis Fungoides)

Diagnosis

• Mycosis fungoides is the most frequent of the cutaneous T-cell lymphomas.

• Erythematous scaling plaques and patches are seen in early localized forms (Figure 34-26).

• Plaques and patches may be hyperpigmented or hypopigmented (Figure 34-27).

• Can progress to diffuse erythema (erythroderma) in later disseminated stage—Sézary syndrome.

• May present as refractory or recurrent eczema.

• Itching and photosensitivity are common.

• May develop into raised fungating lesions (see nasal lesion in Figure 34-27).

FIGURE 34-26 Plaque-type mycosis fungoides on the extremities and trunk. Biopsy a few years before this was read as atopic dermatitis only. Lack of response to medications and the suspicious appearance led to a new biopsy and the correct diagnosis.

(Courtesy of Deborah Henderson, MD.)

FIGURE 34-27 Cutaneous T-cell lymphoma causing large hyperpigmented patches and plaques on this Ethiopian woman. She also has a tumor under her left ala.

(Copyright Richard P. Usatine, MD.)

Biopsy

• Perform a broad shave biopsy or a 4-mm punch biopsy of involved skin.

• Alert the pathologist that this is on your differential diagnosis so that special stains can be done.

• The first biopsy may not show the disease, so consider repeating the skin biopsies if the clinical suspicion remains high.

• Flow cytometry can be done on peripheral blood to look for abnormal lymphocytes.

• Palpate for lymph nodes and consider a lymph node biopsy if the skin biopsies and flow cytometry are not definitive.

• CT of the abdomen and pelvis can be used to look for enlarged lymph nodes and/or splenomegaly.

• Consult specialists if needed—this can be a hard diagnosis to make.

Treatment and Prognosis

• Early stages are treated locally with topical steroids, nitrogen mustards, psoralen and UVA, UVB, and others with excellent prognosis for remission and preventing progression of disease.

• More advanced disease carries a poor prognosis and is treated with a combination of topical medications as above, radiation therapy, and systemic immune system modulators and chemotherapy.

Dermatofibrosarcoma Protuberans

Diagnosis

• Flesh-colored gradually enlarging nodule from one to several or more centimeters in diameter. It may be shiny with a look of multiple deep nodules (Figure 34-28).

• It is of different origin than a dermatofibroma and is not a dermatofibroma becoming malignant.

• May be erythematous or occasionally pigmented.

• Site distribution is typically 45% head and neck and 55% trunk and extremities.¹⁸

FIGURE 34-28 Dermatofibrosarcoma protuberans on the leg.

(Copyright Richard P. Usatine, MD.)

Biopsy

• Use a 4-cm punch biopsy or larger incisional biopsy to provide adequate tissue for diagnosis.

Treatment and Prognosis

• The tumor can invade into adjacent deep structures, becoming locally invasive and highly recurrent.

• Mohs surgery is the preferred treatment to decrease the recurrence rate.

• Wide local excision with 2–4 cm margins is the alternative with lower cure rates.

• One study using pooled data from the literature reported a recurrence rate of 1.3% with Mohs surgery and 20.7% with wide local excision.¹⁹

• Frequent clinical follow-up is indicated for more than 5 years because 25% of recurrences occur after 5 years.¹⁸

Merkel Cell Carcinoma

Diagnoses

• Blue red nodular lesion most commonly of the head and neck (Figures 34-29 and 34-30).

• Mostly older patients and/or immunosuppressed persons.

• Rapidly growing.

• Usually in sun-exposed areas (Figure 34-30).

• Viral etiology with polyoma virus under investigation.²⁰

FIGURE 34-29 Merkel cell carcinoma on the ear.

(Courtesy of Frank Miller, MD.)

FIGURE 34-30 Merkel cell carcinoma on the lip.

(Courtesy of Jeff Meffert, MD.)

Biopsy

• Perform a shave, 4-mm punch, or excisional biopsy.

Treatment and Prognosis

• High rate of nodal metastasis and distant metastasis even for small primary tumors.²¹

• Up to 30% have regional lymph node metastases.²⁰

• Chest x-ray to check for lung cancer as primary site with cutaneous metastasis.

• Wide local excision with 2- to 3-cm margins.

• Best outcome is achieved with multidisciplinary management that includes local radiotherapy and chemotherapy for distant metastases.²⁰^–²²

Coding and Billing Pearls

• Bill for malignant lesion removals after pathology is determined because malignancies have different codes and higher reimbursements.

• When calculating the size of the excised lesion, it is important to include the necessary margins. Therefore, if you are excising a 1-cm basal cell carcinoma with 4-mm margins, you would bill for an excision at 1.8 cm. Do not forget to make these measurements so that you get paid for what you do.

Conclusion

There are choices among the methods of removal of malignant lesions. Small lesions that are not near important structures, have distinct margins, and are not high-grade cancers can usually be managed by clinicians with good basic skills in their office. For high-risk locations and lesions, the best results of complete lesion removal are typically obtained by Mohs micrographic surgery. This chapter has provided a general guideline for malignant lesion management, but as always providers must use their best clinical judgment and adjust the specific treatment based on their individual patient’s needs.

Resources

The American Cancer Society (www.cancer.org) provides information on skin cancers and brochures for patients and clinicians on the ABCDE rules for melanoma.

References

1. Anwar J, Wrone DA, Kimyai-Asadi A, Alam M. The development of actinic keratosis into invasive squamous cell carcinoma: evidence and evolving classification schemes. Clin Dermatol. 2004;22:189-196.

2. Criscione VD, Weinstock MA, Naylor MF, et al. Actinic keratoses: natural history and risk of malignant transformation in the Veterans Affairs Topical Tretinoin Chemoprevention Trial. Cancer. 2009;115:2523-2530.

3. Thai KE, Fergin P, Freeman M, et al. A prospective study of the use of cryosurgery for the treatment of actinic keratoses. Int J Dermatol. 2004;43:687-692.

4. Cox NH, Eedy DJ, Morton CA. Guidelines for management of Bowen’s disease: 2006 update. Br J Dermatol. 2007;156:11-21.

5. Ridky TW. Nonmelanoma skin cancer. J Am Acad Dermatol. 2007;57:484-501.

6. Ahmed I, Agarwal S, Ilchyshyn A, et al. Liquid nitrogen cryotherapy of common warts: cryo-spray vs. cotton wool bud. Br J Dermatol. 2001;144:1006-1009.

7. Ricotti C, Bouzari N, Agadi A, Cockerell CJ. Malignant skin neoplasms. Med Clin North Am. 2009;93:1241-1264.

8. Mosterd K, Krekels GA, Nieman FH, et al. Surgical excision versus Mohs’ micrographic surgery for primary and recurrent basal-cell carcinoma of the face: a prospective randomised controlled trial with 5-years’ follow-up. Lancet Oncol. 2008;9:1149-1156.

9. Szeimies RM. Methyl aminolevulinate-photodynamic therapy for basal cell carcinoma. Dermatol Clin. 2007;25:89-94.

10. Marcil I, Stern RS. Risk of developing a subsequent nonmelanoma skin cancer in patients with a history of nonmelanoma skin cancer: a critical review of the literature and meta-analysis. Arch Dermatol. 2000;136:1524-1530.

11. Arora A, Attwood J. Common skin cancers and their precursors. Surg Clin North Am. 2009;89:703-712.