Squamous Cell Carcinoma, Cutaneous

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Description

  • Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer after basal cell carcinoma (BCC), with >1 million cases diagnosed annually in the United States.
  • Arises from epidermal keratinocytes and accounts for the majority of nonmelanoma skin cancer–related deaths

Epidemiology

Historically, cSCC has been thought to account for 20% of nonmelanoma skin cancers, thus is considered to be the second most common malignancy after BCC. However, recent data indicate that the ratio of BCC to SCC is 1 in the U.S. Medicare population.

Incidence

  • The average age for incidence is around 60 years, more common in men.
  • Incidence increases the closer the person gets to the equator or higher altitude.

Prevalence

>1 million cases of cSCC are diagnosed annually in the United States.

Etiology and Pathophysiology

  • cSCC arises from malignant transformation of keratinocytes in the epidermis, primarily due to cumulative ultraviolet (UV) radiation exposure.
  • UV radiation induces DNA damage and results in mutations in tumor suppressor genes (e.g., TP53) and proto-oncogenes.
  • In immunosuppressed individuals, mutated keratinocytes escape detection and proliferate.

Genetics

Some hereditary disorders have genes that are associated with cSCC. They include:

  • Xeroderma pigmentosum
  • Oculocutaneous albinism
  • Epidermodysplasia verruciformis
  • Genes mutated include: CDKN2A, NOTCH1, Ras, and TP53

Risk Factors

  • Cumulative UV exposure
  • Fair skin types (Fitzpatrick I to III)
  • Gender (more common in men)
  • Increasing age (average age of onset is the mid-60s)
  • Preexisting lesions of actinic keratosis (AK)
  • Immunosuppression
    • Solid organ transplantation
    • HIV/AIDS, non-Hodgkin lymphoma, and chronic lymphocytic leukemia
  • Chronic skin conditions
    • Burn scars, hidradenitis suppurativa, chronic osteomyelitis, discoid lupus erythematosus, lichen planus, lichen sclerosis et atrophicus, and xeroderma pigmentosum
  • Inherited genetic conditions
    • Albinism, epidermolysis bullosa, xeroderma pigmentosum
  • Prior history of ionizing radiation exposure
  • Arsenic exposure
  • Ulcers
  • Bowen disease (squamous cell carcinoma [SCC] in situ)
  • Erythroplasia of Queyrat (SCC in situ of the penis)
  • HPV infection (6, 11, 16, 18)
  • Treatment with BRAF inhibitors (vemurafenib and dabrafenib)

General Prevention

  • Protect skin from sun exposure.
  • Wear sunscreen, hats, and UV-protective clothing.
  • The U.S. Preventive Services Task Force (USPSTF) recommends counseling about minimizing exposure to UV radiation for people aged 6 months to 24 years with fair skin types to decrease their risk of skin cancer (1).

Commonly Associated Conditions

AK is the precursor of cSCC, Bowen disease, and erythroplasia of Querat.

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