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Cutaneous Squamous Cell Carcinoma

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Basics

  • Squamous cell carcinoma (SCC) is a malignant epithelial tumor arising from keratinocytes of the epidermis. Cutaneous (nonmucous membrane) SCC is the 2nd most common form of skin cancer.
  • Lesions most frequently occur on sun-exposed sites of elderly, fair-skinned individuals. Most SCCs arise in solar keratoses (actinic keratoses). Such actinically derived SCCs that develop from solar keratoses are slow-growing, minimally invasive, unaggressive; and the prognosis is usually excellent because distant metastases that arise from these lesions are extremely rare.
  • An SCC may also appear de novo without a preceding solar keratosis. SCCs may also develop from causes other than sun exposure. For example, from an old burn scar or from sites previously exposed to ionizing radiation. An SCC may also emerge from pre-existing human papilloma virus infection (verrucous carcinoma).
  • When metastases from SCC do occur, they often appear on the ears or on the vermilion border of the lips or from tumors >2 cm in diameter. Other risks for metastasis include lesions that arise on mucous membranes, from sites that received ionizing radiation, on the skin of organ transplant recipients, in chronic inflammatory lesions (e.g., discoid lupus erythematosus (1)[C]), and in long-standing scars or cutaneous ulcers (e.g., venous stasis ulcers) or other nonhealing wounds.
  • System(s) affected: Skin/Exocrine
  • Synonym(s): Squamous cell carcinoma of the skin; Epidermoid carcinoma; Prickle cell carcinoma

Epidemiology

  • Predominant age: Elderly population
  • Predominant sex: Males > Females
  • In the US, there are 200,000 new cases each year.
Incidence
  • The escalating incidence in the US 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 US.

ALERT
Bowen disease (SCC in situ) and frank SCC are 2 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.

Risk Factors

  • 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 solar 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
  • 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)
  • Human papillomavirus (HPV) infection (certain subtypes)
  • Chronic scarring and inflammatory conditions
  • Specific genodermatoses (e.g., xeroderma pigmentosum)
Genetics
  • Persons of Irish or Scottish ancestry have the highest prevalence of SCC.
  • SCC is rare in people of African and Asian descent, although it is the most common form of skin cancer in these populations.
  • Patients with oculocutaneous albinism are at greater risk.

General Prevention

Sun-avoidance measures: Sunscreens, hats, sunglasses with UV protection; tinted windshields and side windows in cars; sun-protective garments

Etiology

  • Exact mechanisms are not established; however, UV radiation damages skin cell nucleic acids (DNA), resulting in a mutant clone of the gene p53. This leads to an uncontrolled growth of skin cells. UV radiation also suppresses the immune response, preventing recovery from this damage.
  • Epidemiologic and experimental evidence suggests the following as causative agents: Sunlight (solar radiation), radiation exposure, tanning parlors, psoralen-UV-A (PUVA) phototherapy exposure, inorganic arsenic exposure, coal tar, and other oil derivatives
  • Immunosuppression by medications or disease such as HIV/AIDS

Commonly Associated Conditions

  • Solar keratosis (some investigators consider a solar keratosis to be an early SCC, although relatively few ultimately are found to develop into an SCC)
  • Actinic cheilitis (solar keratoses of the mucous membranes of the lips) and leukoplakia of lip
  • Keratoacanthoma
  • Cutaneous horn
  • Xeroderma pigmentosum, albinism, and vitiligo
  • Immunosuppression
  • Chronic skin ulcers, pre-existing scars, and thermal burns

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