Squamous Cell Carcinoma, Cutaneous
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- Squamous cell carcinoma (SCC) is a malignant epithelial tumor arising from epidermal keratinocytes. Cutaneous (nonmucous membrane) SCC is the second most common form of skin cancer.
- Lesions most frequently occur on sun-exposed sites of elderly, fair-skinned individuals. Most SCCs arise in actinic keratoses (solar keratoses). SCCs that develop from actinic keratoses are slow-growing, minimally invasive, and unaggressive. Thus, the prognosis of an SCC arising from an actinic keratosis is usually excellent because distant metastases are extremely rare.
- An SCC may also appear de novo without a preceding actinic keratosis or emerge from a preexisting human papillomavirus (HPV) infection (verrucous carcinoma).
- SCCs may develop from causes other than sun exposure such as within an old burn scar or on sites previously exposed to ionizing radiation.
- Metastases are more likely to occur in thicker tumors >6-mm deep (1). Other risk factors for metastases include lesions that arise on the ears, the vermilion border of the lips, or on mucous membranes. An SCC located on sites that received ionizing radiation on the skin of organ transplant recipients, in chronic inflammatory lesions (e.g., discoid lupus erythematosus), in long-standing scars or cutaneous ulcers (e.g., venous stasis ulcers), or other nonhealing wounds, also have an increased rate of metastasis.
- System(s) affected: skin/exocrine
- Synonym(s): squamous cell carcinoma of the skin; epidermoid carcinoma; prickle cell carcinoma
- Predominant age: elderly population
- Predominant sex: males > females
- In the United States, >700,000 new cases each year
- The escalating incidence in the United States is due to an increase in sun exposure in the general population, aging of the population, earlier and more frequent diagnosis of SCC, and the increase of immunosuppressed patients.
- The incidence is highest in Australia and in the Sun Belt of the United States.
Bowen disease (SCC in situ) and frank SCC are two of the few skin cancers that should be considered in African Americans. Such non–sun-related SCCs tend to arise on the extremities de novo, in an old scar, or in a lesion of discoid lupus erythematosus.
Etiology and Pathophysiology
- Exact mechanisms are not established; however, SCC is thought to arise from a multistep process that begins with a single mutated keratinocyte.
- UV radiation damages skin cell nucleic acids (DNA), resulting in a mutant clone of the tumor suppressor gene p53. This leads to an uncontrolled growth of skin cells containing a mutated p53 gene. Additional mutations in genes controlling cellular proliferation and/or death lead to squamous cell dysplasia, which then progresses to SCC in situ and later invasive SCC that has the potential for metastasis.
- Cumulative UV radiation (including tanning salons, and psoralen-UV-A [PUVA] phototherapy) over a lifetime is the major etiologic factor in SCC (2)[A].
- A high prevalence of HPV DNA from SCC tissue has been noted in immunocompromised as well as immunocompetent specimens of SCC tissue (3).
- Other causative agents: ionizing radiation exposure, inorganic arsenic exposure, coal tar, and other oil derivatives
- Immunosuppression by medications or disease such as HIV/AIDS
- Persons of Irish or Scottish ancestry have the highest prevalence of SCC.
- Caucasians with the red hair/fair skin phenotype (associated with certain variant alleles of the human melanocortin-1 receptor [MC1R]) are predisposed to SCC.
- SCC is rare in people of African and Asian descent, although it is the most common form of skin cancer in these populations.
- Older age
- Male sex: However, incidence is increasing in females due to lifestyle changes (e.g., suntan parlors, shorter dresses).
- Chronic sun exposure: SCC is noted more frequently in those with a greater degree of outdoor activity (e.g., farmers, sailors, gardeners).
- Patients with multiple actinic keratoses
- Personal or family history of skin cancer
- Northern European descent
- Fair complexion, fair hair, light eyes
- Poor tanning ability, with tendency to burn
- Organ transplant recipients, chronic immunosuppression (especially azathioprine, voriconazole, or sirolimus) (4)
- Exposure to chemical carcinogens (e.g., arsenic, tar) or ionizing radiation
- Therapeutic UV and ionizing radiation exposure
- Defects in cell-mediated immunity related to lymphoproliferative disorders (chronic lymphocytic leukemia [CLL], lymphoma)
- HPV infection
- Chronic scarring and inflammatory conditions
- Specific genodermatoses (e.g., xeroderma pigmentosum, oculocutaneous albinism, and dystrophic epidermolysis bullosa)
Sun-avoidance measures: sunscreens, hats, clothing, and sunglasses with UV protection; tinted windshields and side windows in cars; sun-protective garments
Commonly Associated Conditions
- Some investigators consider an actinic keratosis to be an early SCC, although relatively few ultimately are found to develop into an SCC.
- Actinic cheilitis and leukoplakia of the mucous membranes of the lips
- Cutaneous horn (see following discussion)
- Xeroderma pigmentosum albinism
- Chronic skin ulcers, preexisting scars, burns