Squamous Cell Carcinoma of Skin

Skin cancers are the most common cancers diagnosed.¹ After malignant melanoma and basal cell carcinoma (BCC), squamous cell carcinoma (cSCC) is the third most common form of skin cancer. The incidence is rising worldwide² and although not a cause of high mortality considerable cost and morbidity is attached to cSCC and treatment for cSCC.

• The incidence is about 10,000 per year in England and Wales.
• About 20% of nonmelanoma skin cancers are caused by cSCC and 80% by BCC.
• Age. There is a rising incidence with age.
• Race. The incidence is higher in caucasians.
• Living close to the equator. Unsurprisingly the rise in UVR exposure produces more cases of cSCC in populations in equatorial zones.
• Men are more commonly affected. Head and neck exposure to UVR is probably responsible for this.^1,2
• Skin cancers are the most common cancers diagnosed and incidence is rising across the world despite knowledge and education about prevention.

Risk results from a combination of factors which promote cSCC and the host response to these factors.

• An aging population.
• Improvement in awareness and detection.
• Social and environmental factors:
  • Use of tanning beds
  • Holidays 'in the sun'
  • Ozone depletion and climate change
• Other possible contributory factors:
  • More patients who are immunosuppressed
  • Rising incidence of HPV infection

The hallmark of cSCC is malignant transformation of normal epidermal keratinocytes. UVR causes DNA damage by producing pyrimidine dimers. It appears that this causes mutations and loss of function in important tumour suppressor genes such as TP53. Many other genetic defects which cause failure in the skin cells repair and defence mechanisms are being discovered. These combine and contribute to keratinocytes undergoing clonal expansion and progression to invasive cSCC.

History

• A knowledge of risk factors is helpful in identifying individuals at risk. Lifelong sun exposure, occupational history (including exposure to chemicals or radiation), any immunosuppression, past and current medical history are all important to ask about.
• Typically cSCC presents as a non-healing ulcer or growth in one of the higher risk sun-exposed areas.
• A history of pain or any neurological symptoms may indicate involvement of peripheral nerves.

General examination

About 70% of cSCCs appear on the skin of the head and neck.³ A useful series of photographs can be found in references from the American Academy of Family Physicians.^5,3The skin should be thoroughly examined with special attention given to:

• High risk areas of the body. The most high risk areas are:
  • Lower lip
  • Pinna, particularly the upper sun-exposed parts
  • Periauricular parts of forehead and scalp
  The more sun exposed areas differ somewhat between men and women:
  • In men these are face,backs of hands, head and ears particularly.
  • In women these are face, backs of hands, lower legs, anterior neck and chest.
• Areas of skin showing actinic damage.³ Multiple actinic keratoses are associated with an estimated 10% lifetime risk of skin cancer.
• Areas where there are other precancerous lesions such as:
  • Bowenoid change
  • Leukoplakia
  • Erythroplasia of Queyrat
  • Skin around areas of chronic inflammation

Assessment of a specific lesion

After a thorough head and neck examination the appearance of any suspect skin lesion should be described in detail.

• The typical appearance of a cSCC is of a shallow ulcer with rolled (or heaped- up) edges. Often the ulcer is covered with a plaque.
• The exact appearance will naturally vary according to the site and the extent of disease.
• Lesions at high risk of metastasis are:
  • Greater than 2 cm diameter.
  • Lesions at certain sites, particularly external ear and lip.
• Lesions sited where removal may have both prognostic and therapeutic implications are:
  • Those sited near any vital structures.
  • Lesions close to eyes or important neurovascular areas. Perineural invasion occurs in between 10 and 15% of lesions. Cranial nerves should be examined as these (particularly facial and trigeminal nerves) may be involved.
• Regional lymph nodes should be carefully examined. They are involved in around 5% of cases, more often in larger or less well differentiated tumours.

There are a number of important conditions which can produce similar looking skin lesions:

• Keratoacanthoma (can be difficult to differentiate even histologically)
• Basal cell carcinoma
• Malignant melanoma (particularly amelanotic malignant melanomas)
• Solar keratosis³
• Pyogenic granuloma
• Seborrhoeic warts (especially if traumatised or infected)
• Plantar warts or veruccas (beware periungal cSCC)

• Skin biopsy:
  • Excisional biopsy (whole lesion excised):
    • Small lesions which are accessible and not in cosmetically sensitive areas or near to vital structures can be removed completely.
    • For most lesions this can be performed under local anaesthesia.
    • Minor surgery procedures in primary care are preferred by patients.
    • The full thickness of skin should be taken to determine depth of spread.
    • The excision should be well wide of the margins to achieve clearance.
    • Shave biopsies should not be performed.
  • Incisional or punch biopsy (part of lesion excised) is appropriate:
    • If the lesion is large.
    • In cosmetically sensitive areas.
    • When close to vital structures.
    • Further surgery is performed according to histology.
• In advanced stages of disease further investigations to assess the extent of disease may be required:
  • Imaging including CT (bone or soft tissue spread, particularly cervical lymph nodes) and MRI scanning (particularly for head and neck spread, perineural invasion).

• Treatment of precancerous lesions (some carcinoma in situ and actinic keratosis):
  • Topical 5-fluorouracil (Efudex) and imiquimod. Topical NSAIDS have also been used for actinic keratoses.
  • Cryotherapy with liquid nitrogen
  • Curettage and cautery
  Care should be taken not to treat cSCC with these methods as it then becomes impossible to diagnose and assess the adequacy of treatment. Where cSCC is suspected surgical excision and histological diagnosis is required.
• Treatment of cSCC. There are 2 surgical options:
  • Complete or primary surgical excision.
  • Mohs micrographic surgery.⁷
• Radiotherapy. This is reserved for patients unable to have surgical excision.
• Chemotherapy. Results for chemotherapy generally have been disappointing. However epidermal growth factor receptor inhibitors may be useful adjuncts to surgery.

Complications arise from metastasis and local invasion.

The tumour classification and staging systems are designed with the hope of producing prognostic guidelines. However in individual cases, even with similar tumour characteristics, the prognosis can vary with a range of other factors (age, degree of sun exposure, other diseases coexisting with the SCC). The experience of the treating doctors and surgeons have an influence on the accuracy of prognostic prediction.
Broadly speaking:

• Early stage tumours will have a better than 90% 5 year survival.
• Patients with metastatic lymph node disease have around a 30% 5 year survival.

Avoiding sun exposure is the key to prevention.⁸ The American Academy of Dermatology and the American Cancer Society recommend annual skin examination for all patients over age 40 years.³