Squamous Cell Carcinoma of Skin

Primary cutaneous squamous cell carcinoma (SCC) is a malignant tumour that arises from the keratinising cells of the epidermis or its appendages. It is locally invasive and has the potential to metastasise to other organs of the body.¹

• Skin cancers are the most common cancers diagnosed and incidence is rising across the world despite knowledge and education about prevention.
• The incidence of SCC is about 10,000 per year in England and Wales.
• The incidence is rising worldwide.³
• About 20% of non melanoma skin cancers are caused by SCC and 80% by basal cell carcinoma (BCC).
• There is a rising incidence with age.
• The incidence is higher in caucasians.
• Living close to the equator: the rise in UVR exposure produces more cases of SCC in populations in equatorial zones.
• Men are more commonly affected, probably because of greater head and neck exposure to UVR.^4,3

Chronic UVR exposure is the most important risk factor. This helps explain the very high rates of skin cancer in countries like Australia where fair skinned, susceptible people are put at risk by sun exposure.

• External risk factors:
  • Ultraviolet light (therefore increased risk with holidays in the sun, outdoor occupations and leisure pursuits, and using tanning beds)
  • Immunosuppression
  • Chemical carcinogens:⁵
    • Arsenic and chromium
    • Soot (scrotal cancers in chimney sweeps)
    • Tar and pitch oils
  • Human papilloma virus infection
  • Ionising radiation exposure
• Host responses:
  • Susceptibility to ultraviolet light exposure:
    • Fair skin (skin that tans poorly)
    • Blonde or red hair
  • Chronic inflammation:
    • Near chronic ulcers- Marjolin's ulcers
    • Around chronic sinuses (for example osteomyelitis)
    • Lupus vulgaris (chronic form of cutaneous tuberculosis)
  • Genetic conditions (such as xeroderma pigmentosum and albinism)
• Pre-malignant conditions, e.g. Bowen's disease, actinic keratoses. Keratoacanthomas may rarely progress to squamous cell carcinoma.

• Those that are high risk have a high recurrence rate after treatment and may metastasise:
• Histological features: poorly differentiated, perineural invasion, depth greater than 4 mm or extending to subcutaneous tissue (Clark level 5).
• Sites: lip, ears, non-sun-exposed sites, e.g. penis, scrotum and soles of feet; in areas of previous injury e.g. burns, irradiation and chronic ulcers.
• Other factors are lesions greater than 2 cm diameter, immunosuppression and a previously treated lesion.

SCC usually presents as an indurated nodular keratinising or crusted tumour that may ulcerate, or it may present as an ulcer without evidence of keratinisation.¹

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 SCC 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 SCCs appear on the skin of the head and neck.² A useful series of photographs can be found in references from the American Academy of Family Physicians.^6,2The 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.² 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

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 keratosis²
• Pyogenic granuloma
• Seborrhoeic warts (especially if traumatised or infected)
• Plantar warts or veruccas (beware periungal SCC)

Investigation is primarily by visual inspection and removal for histology where necessary.⁷

• 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 (see separate articles on Minor Surgery in Primary Care).
    • For most lesions this can be performed under local anaesthesia.
    • 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).

• Refer a patient presenting with skin lesions suggestive of skin cancer or in whom a biopsy has confirmed skin cancer to a team specialising in skin cancer.
• Refer patients with persistent or slowly evolving unresponsive skin conditions with uncertain diagnosis to a dermatologist.
• Refer urgently patients:
  • Non-healing keratinising or crusted tumours larger than 1 cm with significant induration on palpation. They are commonly found on the face, scalp or back of the hand with a documented expansion over 8 weeks.
  • Who have had an organ transplant and develop new or growing cutaneous lesions as squamous cell carcinoma is common with immunosuppression but may be atypical and aggressive.
  • With histological diagnosis of a squamous cell carcinoma.

For most patients with non melanoma skin cancer (NMSC) no formal staging beyond clinical examination for lymphadenopathy is required.⁷

• There should be two levels of multidisciplinary teams: local hospital skin cancer multidisciplinary teams (LSMDTs) and specialist skin cancer multidisciplinary teams (SSMDTs).
• People with precancerous skin lesions should be either treated entirely by their GP or referred for diagnosis, treatment and follow-up to doctors working in the community who are members of the LSMDT/SSMDT.
• If there is any doubt about the diagnosis, people with precancerous lesions should be referred directly to their local hospital skin cancer specialist. Where appropriate, follow-up of these patients may be undertaken by their own GP.
• All patients with a squamous cell carcinoma or where the diagnosis is uncertain should be referred urgently to a doctor trained in the specialist diagnosis of skin malignancy, normally a dermatologist, who is a member of either an LSMDT or an SSMDT.
• In England the target for patients with SCC referred through the 2-week urgent GP referral route is that they must start their first definitive treatment within 62 days of GP referral. For all other patients with SCC in England the target is that they must start their first definitive treatment within 31 days of the decision to treat.
• Patients with a high risk of recurrence of skin cancer or of new primary cancers should normally be followed up in hospital but should still be instructed in self examination and provided with written and photographic information.

Management options⁷

The standard effective treatment is complete surgical excision and all excised specimens should be sent for histopathological examination. Where the other non-surgical treatments exclude histological confirmation of the diagnosis, an incisional biopsy for confirmation of the diagnosis should usually be obtained before treatment. Other surgical and non-surgical procedures include:

• Curettage and cautery/electrodesiccation:
  • Performed using a curette to remove soft material from the tumour. The base of the tumour is then destroyed, using either hyfrecation or cautery.
  • This may be used to treat small (less than 1 cm) in situ SCCs and precancerous lesions.
  • It is safe and well tolerated, and usually produces a good cosmetic outcome.
  • It is suitable for patients with multiple lesions.
  • The histology may be difficult to interpret as the lesion may be incompletely removed and margins of excision cannot be assessed optimally.
• Cryotherapy/cryosurgery:
  • Is a cost-effective treatment and is well established for small in situ SCCs and precancerous lesions.
  • Histology is not available unless an incisional biopsy is taken first.
• Topical treatment:
  • Imiquimod 5% cream is a effective in treating actinic keratosis.
  • Fluorouracil (Efudix® 5% cream) is licensed for ‘superficial malignant and precancerous skin lesions’.
  • Diclofenac 3% gel is licensed for the treatment of actinic keratoses.
• Photodynamic therapy (PDT):
  • Involves the use of light therapy in combination with a topical photosensitising agent to destroy cancer cells.
  • Is used in the treatment of in situ SCCs and actinic keratosis.
  • Evidence of efficacy for treating invasive squamous cell carcinomas is limited, recurrence rates are high, there is a risk of metastasis and retreatment may be necessary.⁹
• Mohs micrographic surgery:
  • Is a precise technique in which excision of the skin lesion is carried out in stages and each stage checked histologically.
  • It is advocated for use in cases where it is critical to obtain a clear margin while preserving the maximum amount of normal surrounding tissue.
  • This procedure is more often used in the treatment of basal cell carcinomas.
• Radiotherapy:
  • Is a useful treatment for patients who cannot or prefer not to be treated by surgery.
  • The cure rates are over 90% for most skin lesions, but the long-term cosmetic outcome, particularly for young patients, is inferior to that following other treatments.
  • The same area cannot be treated twice and so, if there is a recurrence, surgery is required, which may be more difficult than if the lesion had been removed surgically to start with.
  • Radiotherapy can also be used in cases when the margins of excision appear to be incomplete on histopathological examination.
  • Radiotherapy is curative for some cases of advanced inoperable disease.
  • Radiotherapy also has a role in the palliative treatment of patients with large, inoperable and recurrent SCC, or if there are inoperable metastases in lymph nodes or elsewhere.
  • Radiotherapy has a role in adjuvant treatment of extracapsular nodal disease following neck dissection.

• Site: tumour location in order of increasing metastatic potential:
  • SCC arising at sun-exposed sites excluding lip and ear.
  • SCC of the lip.
  • SCC of the ear.
  • Tumours arising in non-sun-exposed sites (e.g. perineum, sacrum, sole of foot).
  • SCC arising in areas of radiation or thermal injury, chronic draining sinuses, chronic ulcers, chronic inflammation or Bowen's disease.
• Diameter: tumours greater than 2 cm in diameter are twice as likely to recur locally and three times as likely to metastasise.
• Depth: tumours greater than 4 mm in depth (excluding surface layers of keratin) or extending down to the subcutaneous tissue (Clark level V) are more likely to recur and metastasise compared with thinner tumours.
• Histological differentiation: poorly differentiated tumours have a poorer prognosis, with more than double the local recurrence rate and triple the metastatic rate of better differentiated SCC.
• Tumours with perineural involvement are more likely to recur and to metastasise.
• Host immunosuppression: tumours arising in patients who are immunosuppressed have a poorer prognosis.
• Previous treatment and treatment modality: the risk of local recurrence depends upon the treatment modality:
  • Locally recurrent disease itself is a risk factor for metastatic disease.
  • Local recurrence rates are considerably less with Mohs' micrographic surgery than with any other treatment modality.

• In individual cases, even with similar tumour characteristics, the prognosis can vary with a range of other factors, e.g. age, degree of sun exposure, other diseases coexisting with the SCC.
• 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.¹⁰
• Secondary prevention by early detection and effective management is also very important.
• The American Academy of Dermatology and the American Cancer Society have recommended annual skin examination for all patients over age 40 years.²