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Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer after BCC with over 400,000 new cases annually in the United States. Generally, the incidence ratio of BCCs over SCCs is 4:1. However, this ratio is reversed in solid organ transplant patients where SCCs are more common than BCCs by a 4:1 ratio.2 Unlike BCCs, SCCs have the potential for local and distant metastasis. UV exposure is the most common cause of SCC.
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SCCs are malignant tumors of epidermal keratinocytes. AKs are often precursor lesions for SCC. Intense UV exposure or cumulative UV DNA damage may lead to p53 tumor suppressor gene mutations and development of AKs and ultimately SCC.11 Other factors that have been associated with SCC development include human papillomavirus (HPV), burns and scars, ionizing radiation, chronic inflammation, arsenic exposure, and tobacco use. Certain genetic syndromes can also promote SCC development, including xeroderma pigmentosum, oculocutaneous albinism, and dystrophic epidermolysis bullosa.11
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Clinical Presentation
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History and Physical Examination
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As with BCCs, patients may complain of a wart or pimple-like lesion on sun-exposed skin that grows slowly with episodes of bleeding and tenderness. Most SCCs occur on sun-exposed areas such as the face, scalp in balding men, dorsal hands and forearms, and lower legs especially in women. SCCs commonly arise from an area of extensive photodamage with diffuse AK. They typically resemble wart-like lesions that occasionally bleed and are tender to the touch.
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There are several subtypes of SCC:11
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Squamous cell carcinoma in situ is limited to the epidermal layer without dermal invasion. Unlike an actinic keratosis that has partial thickness atypia, SCC in situ has full thickness atypia and often is described as an intraepidermal carcinoma. SCC in situ typically occurs on sun-exposed areas with extensive photodamage. It appears as a rough, erythematous, keratotic papule or plaque that often resembles an AK, but with more induration or tenderness (Figure 17-7). SCC in situ and AKs may be present on the same lesion with gradual transition from partial atypia to full thickness atypia.
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Bowen's disease is a SCC in situ that presents as a well-demarcated, erythematous plaque with minimal scale and is often located on the lower extremities particularly in women (Figure 17-8). This lesion is often misdiagnosed as eczema or psoriasis or even superficial BCC. Any SCC in situ has potential for becoming invasive if not treated appropriately.
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Erythroplasia of Queyrat is a SCC in situ on the penile shaft, usually in uncircumcised men. This lesion appears as a non-scaly, erythematous, thin plaque on the shaft or corona of the penis (Figure 17-9) that may be present for years and is often misdiagnosed as dermatitis or a candida infection.
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Invasive SCCs have extension into the dermis and beyond and are typically categorized histologically by the grade of keratinocyte differentiation (well, moderate, poor, and infiltrative). Clinically, invasive SCC appears as a solitary hyperkeratotic pink nodule or papule on sun-exposed areas (Figure 17-10). An invasive SCC has the potential for metastasis, especially if there is perineural invasion or if the lesions are histologically aggressive with poor differentiation or infiltrative pattern. Lower lips and ears are particularly susceptible areas for SCC development with potential risk for regional lymph node metastasis. Solid organ transplant patients can develop SCCs in all areas with risk for metastasis and local recurrence.
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Keratoacanthomas are invasive SCC with a unique clinical history and presentation. They appear and grow quickly in matter of weeks and appear as a solitary symmetrical erythematous nodule with a central hyperkertotic core that resembles a larger molluscum contagiosum lesion (Figure 17-11).
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Verrucous Carcinomas are invasive SCCs that present as verrucous warty-like plaques usually on plantar feet or on distal fingers. These long-standing lesions are often treated for years as common warts without resolution. Verrucous carcinomas are thought to arise from HPV-induced abnormal keratinocytes.
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The histopathology of SCC in situ shows abnormal keratinocytes involving the entire thickness of the epithelium. Invasive SCCs are graded based on degree of keratinocyte differentiation. Well-differentiated SCCs have a higher level of keratinization and are more localized. Poorly differentiated SCCs have no or very limited keratinization and less differentiation. These lesions may have a more spindle cell appearance with higher risk of metastasis and local recurrence. They may have perineural invasion and involve deeper layers of the skin with wider subcutaneous extension. Infiltrative SCC have a desmoplastic scar-like appearance with single cell strands infiltrating the dermis and subcutis. These lesions may be missed with typical hematoxylin and eosin (H&E) staining and may need specialized immunohistochemical stains.
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A SCC typically presents as a hyperkeratotic erythematous papule or plaque on sun damaged skin.
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Differential Diagnosis
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✓ Viral wart: Presents as a hyperkeratotic papule, but with less redness, typically on palmar and plantar surfaces.
✓ BCC: Tends to be less scaly and have a more pearly surface with telangiectasia.
✓ Seborrheic keratosis: Tends be more well defined with a verrucous pigmented keratotic surface.
✓ Dermatitis: Tends to have a less well-defined border than a SCC and responds to topical steroids.
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Suspected lesions should be biopsied for confirmation of the diagnosis of SCC as well as histologic grading if indicated. Shave biopsy is sufficient if the lesion is adequately sampled into the superficial dermis. An invasive SCC may be under diagnosed as a SCC in situ or an AK if the biopsy transects through the atypical epithelium only.
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Most SCCs are treated by surgical removal either by fusiform excision or Mohs micrographic surgery. For fusiform excision, the typical margin is 4 mm as in excision of BCCs. Mohs micrographic surgery indications are listed in Table 17-1. For SCC with poor differentiation or spindle cell features, the risk for metastasis is higher and proper staging with sentinel lymph node biopsy or lymph node dissection as well as radiologic examination is recommended.11
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Electrodessication and currettage, topical treatments such as imiquimod, and PDT have been successful in the treatment of SCC in situ lesions. However, the clinician must be aware of the risk of recurrence and metastatic disease and should limit the usage of these treatments for selected SCCs.
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Indications for Consultation
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Generally, a well-differentiated SCC may be excised appropriately by a surgically trained healthcare provider. Any SCC in high-risk area or a tumor with more aggressive features should be evaluated by a dermatologist and dermatologic surgeon for proper diagnosis, staging, and treatment.
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