Cutaneous squamous cell carcinoma (SCC) is a common type of keratinocyte cancer, or non-melanoma skin cancer. It is derived from cells within the epidermis that make keratin — the horny protein that makes up skin, hair and nails.
Cutaneous SCC is an invasive disease, referring to cancer cells that have grown beyond the epidermis. SCC can sometimes metastasise and may prove fatal.
Intraepidermal carcinoma (cutaneous SCC in situ) and mucosal SCC are considered elsewhere.
Risk factors for cutaneous SCC include:
More than 90% of cases of SCC are associated with numerous DNA mutations in multiple somatic genes. Mutations in the p53 tumour suppressor gene are caused by exposure to ultraviolet radiation (UV), especially UVB (known as signature 7). Other signature mutations relate to cigarette smoking, ageing and immune suppression (eg, to drugs such as azathioprine). Mutations in signalling pathways affect the epidermal growth factor receptor, RAS, Fyn, and p16INK4a signalling.
Beta-genus human papillomaviruses (wart virus) are thought to play a role in SCC arising in immune-suppressed populations. β-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38 have also been associated with an increased risk of cutaneous SCC in immunocompetent individuals.
Cutaneous SCCs present as enlarging scaly or crusted lumps. They usually arise within pre-existing actinic keratosis or intraepidermal carcinoma.
Cutaneous SCC is nearly always treated surgically. Most cases are excised with a 3–10 mm margin of normal tissue around a visible tumour. A flap or skin graft may be needed to repair the defect.
Other methods of removal include:
Major features
Minor features
White or pale skin colour is an independent but significant risk factor for melanoma across diverse ethnic groups. However, people of all skin colours with a family history of melanoma are at increased risk of developing melanoma due to a genetic predisposition.
In skin of colour, it can be harder to identify melanomas, their growth phase, and their pattern as the surrounding skin may mask or match the colour of the melanoma.
People with skin of colour tend to have:
There is a great deal of evidence to show that very careful sun protection at any time of life reduces the number of SCCs. This is particularly important in ageing, sun-damaged, fair skin; in patients that are immune suppressed; and in those who already have actinic keratoses or previous SCC.
Oral nicotinamide (vitamin B3) in a dose of 500 mg twice daily may reduce the number and severity of SCCs in people at high risk.
Patients with multiple squamous cell carcinomas may be prescribed an oral retinoid (acitretin or isotretinoin). These reduce the number of tumours but have some nuisance side effects.
What is the outlook for cutaneous squamous cell carcinoma?
Most SCCs are cured by treatment. A cure is most likely if treatment is undertaken when the lesion is small. The risk of recurrence or disease-associated death is greater for tumours that are > 20 mm in diameter and/or > 2 mm in thickness at the time of surgical excision.
About 50% of people at high risk of SCC develop a second one within 5 years of the first. They are also at increased risk of other skin cancers, especially melanoma. Regular self-skin examinations and long-term annual skin checks by an experienced health professional are recommended.
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