ANATOMY
Skin is often referred to as the largest organ in the body, which, by mass, it is. The importance of the skin as a functional barrier to loss of fluids and protection from microorganisms is immediately apparent to anyone caring for patients with significant burns. The performance of these functions requires a highly specialized multi-layer construction.
The outer layer, the epidermis, comprises four layers. Moving inward, they are the keratin layer, consisting of dead skin cells, the granular layer, the squamous layer, and the basal layer. Epithelial cells originate in the basal layer and are pushed outward over time to form the upper layers. These basal cells are strongly attached to the basement membrane. Moving inward, the dermis is composed of collagen, elastin, and glycosaminoglycans. Cellular components are typically fibroblasts. Below the dermis is a layer of subcutaneous fat that is home to sweat glands, hair follicles, and sebaceous glands.
OVERVIEW AND PREVENTION
Skin cancer is the most common malignancy in the United States, with the less aggressive forms, basal cell and squamous cell, being much more prevalent than melanoma skin cancer. Approximately 1 million nonmelanoma skin cancers will be diagnosed in the United States in 2007, but only 2,000 deaths will be attributable to the disease. The incidence of these types of cancers is increasing in the United States.
It is generally accepted that these cancers are due to sun exposure. Professional and public education campaigns regarding the dangers of excessive sun exposure are expected to decrease the incidence over time. Methods to reduce sun exposure include limiting daytime activity during peak sun hours, between 11 AM and 3 PM; using protective clothing, including long sleeves and hats; and using high-opacity sunscreens. Because sunburns seem to be associated with higher rates of skin cancer, these should be avoided.
Skin cancer seems to be more prevalent in people with light skin or numerous moles. Regular check-ups for both these groups are critical to make an early diagnosis and initiate treatment.
BASAL CELL CARCINOMA
Basal cell carcinoma (BCC) is the most common form of skin cancer in Caucasians. It is rare in Asians and exceedingly rare in darkly pigmented individuals. The predominant cause is long-term excess exposure to ultraviolet B (UVB) radiation. Accordingly, BCC is a disease of adults, and tumors arise from sun-exposed skin, namely the head and neck. The cellular origin of BCC has traditionally been thought to be the basal cell of the epidermis. More recently, an alternative theory posits that the originating cell type is a pluripotent epithelial cell. BCC is categorized into three types: noduloulcerative, superficial, and sclerosing.
NODULOULCERATIVE BASAL CELL CARCINOMA
Lesions have a pearly, dome-shaped, nodular appearance, with associated telangiectasia and an ulcerated center (see Color Plate 16). Telangiectasia is secondary to
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tumor-induced angiogenesis, and ulceration results from outgrowth of the local blood supply. Noduloulcerative lesions are the most common type of BCC.
Tumors <1 cm in diameter are rarely invasive and can be treated with cautery and curettage or cryosurgery. Tumors >1 cm are treated with surgical excision. High-risk sites of tumor growth are areas with underlying bone and cartilage (i.e., nose, ear), because the growing tumor tends to track along these structures. Such tumors have a high recurrence rate. Therefore, high-risk tumors and recurrent tumors should be treated with Moh micrographic surgery to ensure complete excision. In this procedure, the entire visible tumor is excised and the margins are carefully marked. Frozen sections are then examined to determine whether the tumor has been completely excised, and if not, to guide further resection. The wounds are not closed until the pathologist determines that all margins are negative. In this way, a maximum amount of skin and soft tissue can be saved, providing a good cosmetic result.
SUPERFICIAL BASAL CELL CARCINOMA
The second most common BCC is the superficial type. Lesions usually appear on the trunk and proximal extremities and clinically resemble thin, scaly, pink plaques with irregular margins (see Color Plate 17). These horizontally expanding tumors are often dismissed as dermatitis; subsequently, tumors may reach diameters of several centimeters by the time of diagnosis. By this late stage, ulceration and deep dermal invasion are present. Standard treatment has been wide-margin excision, with skin grafting if necessary. However, this approach may be unacceptably morbid, leaving a large skin defect. Recently, topical chemotherapy with fluorouracil, cryosurgery, and cautery/curettage has shown cure rates similar to those of traditional wide excision.
SCLEROSING BASAL CELL CARCINOMA
Sclerosing BCC is the least common type. The anatomic distribution is similar to that of the noduloulcerative type, but histologically, the lesions appear as narrow cords of tumor cells encased in a proliferation of connective tissue. Macroscopically, lesions are smooth, atrophic, and indurated and easily mimic scar tissue. This deceptive appearance is unfortunate, because sclerosing tumors are more aggressive than other basal cell tumor types. The growth pattern follows tissue planes and neurovascular bundles, resulting in deep soft tissue invasion. Moh micrographic surgery is the preferred management technique.
MELANOMA
Melanoma is the most frequent cause of death of all skin cancer types. It results from malignant transformation of the normal melanocyte, usually located in the basal layer of the epidermis. Many melanomas are curable by surgical excision.
PATHOGENESIS
Ultraviolet (UV) light is suspected to play a role in the development of all types of skin cancer, including melanoma. Although the precise etiologic role of UV light in the malignant transformation of skin cells remains unresolved, both ultraviolet A (UVA) and UVB are thought to have carcinogenic potential. UVA penetrates deep into the dermis, damaging connective tissue and intrinsic skin elasticity. Excessive UVB exposure results in sunburn.
EPIDEMIOLOGY
Melanoma accounts for 5% of all skin malignancies and 3% of all cancers. The diagnosis of melanoma carries a 50% mortality rate in the United States, and the incidence has dramatically increased during the past 10 to 15 years. Many lesions arise from preexisting moles. A mole that shows rapid growth or heterogeneous pigmentation should be evaluated and possibly biopsied to rule out melanoma. Fair-skinned individuals have a higher incidence of melanoma than the general population. The five signs of melanoma can be remembered as the ABCDE's: asymmetric shape, irregular border, mottled color, large diameter, and progressive enlargement.
RISK FACTORS
Risk factors include the following: a mole that shows persistent changes in shape, size, or color; persons having more than 100 nevi; atypical nevi (5% of population); personal history or family history of melanoma; excess
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sun exposure (especially in childhood); fair complexion; and tendency to freckle and sunburn.
MELANOMA TYPES
Superficial spreading melanoma can occur anywhere, on both sun-exposed and nonexposed areas. The average age of diagnosis is 40 to 50 years. Lesions are commonly on the upper back and lower legs. Lesions show heterogeneous pigmentation with irregular margins. The growth phase is radial with horizontal spread (Fig. 23-1).
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Figure 23-1 • Superficial spreading melanoma. Note the central area (whitish gray) of regression. From Goodheart HP. Goodheart's Photoguide of Common Skin Disorders. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2003. |
Lentigo maligna melanoma is usually seen in older individuals, with the average age of diagnosis being 70 years. Lesions appear on sun-exposed surfaces, particularly the malar region of the cheek and temple. Lesions exhibit horizontal spread (Fig. 23-2).
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Figure 23-2 • Lentigo maligna melanoma. Biopsy of this lesion demonstrated invasion into the dermis. From Goodheart HP. Goodheart's Photoguide of Common Skin Disorders. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2003. |
Acral lentiginous melanoma has an unusual distribution in that lesions appear on palms, soles, nail beds, or mucous membranes. The most common mucous membrane site is the vulva. Other sites include the anus, nasopharynx, sinuses, and oral cavity. The average age of diagnosis is 60 years. Spread is in a horizontal pattern.
Nodular melanoma can occur at any site and has a very early malignant potential secondary to a predominantly vertical growth phase. In contrast to the three other melanoma types exhibit which radial growth phases with horizontal spread. Nodular lesions have well-circumscribed borders and uniform black or brown coloring.
PROGNOSIS
As with other cancers, the extent of spread is an important prognostic factor. Stage I denotes local disease <1.5 mm. Stage II denotes local disease >1.5 mm. Stage III denotes regional disease. Stage IV denotes metastatic disease. As indicated in Table 23-1, stage I disease carries a relatively good prognosis as compared with the dismal prognosis of stage IV disease.
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TABLE 23-1 Ten-Year Survival Rates in Patients with Melanoma by Tumor Thickness and Ulceration (n = 4,568)a |
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In melanoma, tumor thickness is inversely related to survival and is the single most important prognostic indicator. Historically, there have been two systems for classifying melanomas: the Breslow thickness scale and Clark level of tumor invasion.
The Breslow scale defines primary melanomas that are <0.76 mm thick as local tumors. These tumors have >90% cure rates after simple excision. Individuals with tumors deeper than 0.76 mm have a significant risk of metastatic disease and worse survival.
Clark levels of tumor invasion provide an anatomic description of tumor invasion. The level of tumor invasion can be used for discussing prognosis and planning surgical management (Fig. 23-3).
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Figure 23-3 • The Clark and Breslow classifications for melanoma. |
TNM staging defines stage I tumors as T1 lesions (≤0.76 mm thick) or as T2 lesions (0.76 to 1.50 mm thick) with negative nodes and no metastases. Stage II tumors are T3 lesions (1.51 to 4.00 mm thick) or T4 lesions (>4.00 mm thick) with negative nodes and no metastases. Stage III tumors have fewer than three regional metastases (N1) and no distant metastases,
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whereas stage IV tumors have metastases in skin or subcutaneous tissue, distant lymph node metastases, or visceral metastases.
TREATMENT
Surgical excision is the treatment of choice for primary melanomas. The size of the surgical margin is based on the thickness of the primary lesion (Table 23-2).
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TABLE 23-2 Suggested Margins for Surgical Excision of Melanoma |
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Most tissue defects are primarily closed without skin grafting. If primary biopsy specimens are found to have tumor-negative margins, no further surgical treatment is required. Primary mucosal melanomas have poor outcomes because disease is usually extensive. Nail bed lesions require amputation at the distal interphalangeal joint for finger primaries and the interphalangeal joint for thumb primaries.
Regarding regional disease, the performance of elective regional lymph node dissection for nonpalpable nodes is not routine. The thickness of the primary melanoma is used to predict the chance of regional lymph node metastases. Thin lesions limited to the epidermis have a low likelihood of lymph node metastasis, whereas thick lesions invading the subcutaneous fat have a higher likelihood of spread. Regional lymphadenectomy is usually only performed for thick lesions with a high likelihood of nodal spread.
Because of the morbidity of formal regional lym-phadenectomy and to increase the ability of detect-ing microscopic nodal involvement with minimal
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invasiveness, the technique of sentinal lymph node biopsy was developed. Using lymphoscintigraphy, the sentinel node of the first-order lymph node basin into which the tumor initially drains is identified. In lymphoscintigraphy, technetium and a sulfur colloid are circumferentially injected around the primary lesion. The technetium drains via lymphatics to the sentinel node, which is identified using a handheld Geiger Counter. The sentinel node is excised and evaluated microscopically for evidence of metastasis. Sentinel lymph node biopsy is usually considered for lesions >1 mm in thickness.
In metastatic disease, individuals with a single identifiable metastatic lesion may benefit from surgical resection. However, resection is generally not recommended for patients with multiple metastatic lesions. Metastatic sites include skin, lung, brain, bone, liver, and the gastrointestinal tract. Treatment options include surgery, radiation, chemotherapy, and isolated limb perfusion.
SQUAMOUS CELL CARCINOMA
Squamous cell carcinoma (SCC) is the second most common form of skin cancer after BCC. Tumors arise from the skin and the oral and anogenital mucosa. Multiple predisposing factors for development of SCC have been identified (Table 23-3).
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TABLE 23-3 Predisposing Factors for Developing Squamous Cell Carcinoma |
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PATHOGENESIS
The predominant cause of most SCC is chronic actinic damage that induces the malignant transformation of epidermal keratinocytes. A similar effect is seen with exposure to ionizing radiation (x-rays and gamma rays). In darkly pigmented individuals, however, most lesions arise from sites of chronic inflammation, such as osteomyelitis and chronic tropical ulcerations. Tumors also arise at mucocutaneous interfaces, secondary to tobacco use or human papilloma virus (HPV) infection. Smokers typically present with ulcerating lip and gum or tongue lesions, whereas invasive cancers of the vulva and penis are seen with HPV infection. Anogenital SCC is linked to infection with HPV types 16, 18, 31, 33, and 35. Immunosuppressed or immunocompromised individuals—namely, transplant recipients on immunosuppressive medication or those with HIV/AIDS— have an increased incidence of SCC and an elevated rate of metastasis. Rarely, tumors arise from old scars (usually sustained secondary to burn injury), which form so-called Marjolin ulcers or burn scar tumors. As a rule, actinically induced cancers infrequently metastasize, whereas tumors arising from other mechanisms have a significantly higher rate of metastasis (Table 23-3).
HISTORY
SCC appears as an indurated nodule or plaque, often with ulceration, which has slowly evolved over time. Most lesions are on sun-exposed areas, such as the face, ears, and upper extremities.
PHYSICAL EXAMINATION
Caucasians exhibit pinkish lesions, whereas darker-skinned individuals have hypo- or hyperpigmented lesions (Fig. 23-4). Regional lymphadenopathy occurs in 35% of SCCs arising in the lip and mouth. Aberrant keratinization is often seen in SCC, occasionally causing the growth of cutaneous horns. Therefore, the base of a cutaneous horn should always be examined for the presence of squamous cell cancer.
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Figure 23-4 • Squamous cell carcinoma. This patient has a nodular, ulcerative lesion on his lip. From Goodheart HP. Goodheart's Photoguide of Common Skin Disorders. 2nd ed. Philadelphia, PA: Lippincott Williams & Wilkins, 2003. |
TREATMENT
The preferred treatment is tumor removal by surgical excision. The remaining defect is closed either primarily for smaller lesions or by skin grafting or flap reconstruction for larger lesions. Cryosurgery or cautery/ curettage can also be used for small tumors.
PROGNOSIS
The overall cure rate for SCC is 90% after treatment. Tumors other than sun-induced SCC have a higher mortality rate because of the greater likelihood of metastasis.
KEY POINTS