What Is Squamous Cell Carcinoma ?
What is Squamous Cell Carcinoma?
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.
Who Gets Squamous Cell Carcinoma?
Risk factors for cutaneous SCC include:
- Age and sex: SCCs are particularly prevalent in elderly males. However, they also affect females and younger adults.
- Previous SCC or another form of skin cancer (basal cell carcinoma, melanoma) are a strong predictor for further skin cancers.
- Actinic keratoses
- Outdoor occupation or recreation
- Smoking
- Fair skin, blue eyes, and blond or red hair
- Previous cutaneous injury, thermal burn, disease (eg, cutaneous lupus, epidermolysis bullosa, leg ulcer)
- Inherited syndromes: SCC is a particular problem with xeroderma pigmentosum, albinism, and epidermodysplasia verruciformis
- Other risk factors include ionising radiation, exposure to arsenic, and immune suppression due to disease (eg, chronic lymphocytic leukaemia) or medicines. Organ transplant recipients have an increased risk of developing SCC.
What Causes Squamous Cell Carcinoma?
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.
What are the Clinical Features of Squamous Cell Carcinoma?
Cutaneous SCCs present as enlarging scaly or crusted lumps. They usually arise within pre-existing actinic keratosis or intraepidermal carcinoma.
- They grow over weeks to months
- They may ulcerate
- They are often tender or painful
- Located on sun-exposed sites, particularly the face, lips, ears, hands, forearms and lower legs
- Size varies from a few millimetres to several centimetres in diameter.
What is the treatment for cutaneous squamous cell 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:
- Shave, curettage, and electrocautery for low-risk tumours on trunk and limbs
- Aggressive cryotherapy for very small, thin, low-risk tumours
- Mohs micrographic surgery for large facial lesions with indistinct margins or recurrent tumours
- Radiotherapy for an inoperable tumour, patients unsuitable for surgery, or as adjuvant.
Major features
- Change in size
- Irregular shape
- Irregular colour
Minor features
- Diameter >7 mm
- Inflammation
- Oozing
- Change in sensation
How do Clinical Features vary in different types of Skin?
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:
- Thicker melanomas at diagnosis and higher mortality rates
- Significantly higher rates of melanomas in areas not exposed to the sun, including the subungual, palmar, and plantar surfaces (eg, acral lentiginous melanoma in Pacific Islanders, blacks, and Asians)
- Non-cutaneous melanomas (eg, mucosal melanoma, ocular melanoma).
How can Cutaneous Squamous Cell Carcinoma be prevented?
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.
- Stay indoors or under the shade in the middle of the day
- Wear covering clothing
- Apply high protection factor SPF50+ broad-spectrum sunscreens generously to exposed skin if outdoors
- Avoid indoor tanning (sun beds, solaria)
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.
