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

Epidemiology²

• Skin cancers are the most common cancers diagnosed and incidence is rising across the world despite knowledge and education about prevention.
• Squamous cell carcinoma (SCC) is the second most common skin cancer (behind basal cell carcinoma (BCC)).¹ The incidence is rising worldwide.³
• The incidence of SCC is about 10,000 per year in England and Wales. The incidence is higher in Caucasians.
• About 20% of non-melanoma skin cancers (NMSCs) are caused by SCC and 80% by BCC.
• There is a rising incidence with age. Men are more commonly affected, probably because of greater head and neck exposure to ultraviolet radiation (UVR).^3,4

Risk factors

Chronic UVR exposure is the most important risk factor. This helps to explain the very high rates of skin cancer in countries like Australia, where fair-skinned, susceptible people are put at risk by sun exposure. The rise in UVR exposure produces more cases of SCC in populations in equatorial zones.

• UV light (therefore there is increased risk with holidays in the sun, outdoor occupations and leisure pursuits, and using tanning beds).
• Susceptibility to UV light exposure: fair skin (skin that tans poorly), blonde or red hair.
• Chemical carcinogens: arsenic and chromium, soot (scrotal cancers in chimney sweeps), tar and pitch oils.⁵
• Human papillomavirus infection.
• Ionising radiation exposure.
• Immunodeficiency.
• Chronic inflammation: near chronic ulcers, around chronic sinuses (e.g. osteomyelitis), lupus vulgaris (chronic form of cutaneous tuberculosis).
• Genetic conditions, e.g. xeroderma pigmentosum and albinism.
• Pre-malignant conditions, e.g. Bowen's disease, areas of skin showing actinic damage.² Multiple actinic keratoses are associated with an estimated 10% lifetime risk of skin cancer. Keratoacanthomas may rarely progress to SCC.

Presentation^2,6

Squamous cell carcinoma (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

• Typically, SCC presents as a non-healing ulcer or growth in one of the higher-risk sun-exposed areas. About 70% of SCCs appear on the skin of the head and neck.²
• The clinical appearance is very variable:
  • A small nodule enlarges and the centre becomes necrotic and sloughs, developing into an ulcer. The tumour therefore usually presents as an ulcerated lesion with hard, raised edges.
  • Slow-growing ulcer or reddish skin plaque.
  • Bleeding may occur from the tumour.
• SCC may give rise to local metastases or spread to local lymph nodes.¹

Differential diagnosis

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 (BCC).
• Malignant melanoma (particularly amelanotic malignant melanomas).
• Solar keratosis.²
• Pyogenic granuloma.
• Seborrhoeic warts (especially if traumatised or infected).
• Plantar warts or veruccas (beware periungual squamous cell carcinoma (SCC)).

Investigations

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 article Minor Surgery in Primary Care - Basic Procedures).
  • 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.

Further investigations:

• In advanced stages of disease, further investigations to assess the extent of disease may be required:
  • Imaging including CT scanning (bone or soft tissue spread, particularly cervical lymph nodes) and MRI scanning (particularly for head and neck spread, perineural invasion).
  • Clinically enlarged nodes should be examined histologically, e.g. by fine needle aspiration or excisional biopsy.¹

Referral⁸

• 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 patients urgently:
  • Who have 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 eight weeks.
  • Who have had an organ transplant and develop new or growing cutaneous lesions, as squamous cell carcinoma (SCC) is common with immunosuppression but may be atypical and aggressive.
  • With histological diagnosis of an SCC.

Staging

For most patients with NMSC, no formal staging beyond clinical examination for lymphadenopathy is required.⁷

Management⁷

• 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 either be 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 (SCC) 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. However, there is little evidence comparing the efficacy of different interventions for primary cutaneous SCCs.⁹ Where the other nonsurgical treatments exclude histological confirmation of the diagnosis, an incisional biopsy for confirmation of the diagnosis should usually be obtained before treatment. Other surgical and nonsurgical 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 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 SCCs is limited, recurrence rates are high, there is a risk of metastasis and retreatment may be necessary.¹⁰
• 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 (BCCs).
• Radiotherapy:
  • Is a useful treatment for patients who cannot be, 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.

Factors affecting metastatic potential of cutaneous squamous cell carcinoma¹

• Site: tumour location in order of increasing metastatic potential:
  • Squamous cell carcinoma (SCC) arising at sun-exposed sites excluding the lip and ear.
  • SCC of the lip.
  • SCC of the ear.
  • Tumours arising in non sun-exposed sites (e.g. the 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.

Prognosis

• 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 co-existing with the squamous cell carcinoma (SCC).
• With increasing depth of invasion of the primary tumour, the risk of nodal metastasis increases and survival decreases.¹¹
• Early-stage tumours will have better than 90% 5-year survival.
• Patients with metastatic lymph node disease have around 30% 5-year survival.

Prevention¹²

• Avoiding sun exposure is the key to prevention.¹²
• 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 the age of 40 years.²

Document references

1. Multi-professional Guidelines for the Management of the Patient with Primary Cutaneous Squamous Cell Carcinoma, British Association of Dermatologists (2009)
2. Jerant AF, Johnson JT, Sheridan CD, et al; Early detection and treatment of skin cancer. Am Fam Physician. 2000 Jul 15;62(2):357-68, 375-6, 381-2. [abstract]
3. Foo CC, Lee JS, Guilanno V, et al; Squamous cell carcinoma and Bowen's disease of the skin in Singapore. Ann Acad Med Singapore. 2007 Mar;36(3):189-93. [abstract]
4. Massari LP, Kastelan M, Gruber F; Epidermal malignant tumors: pathogenesis, influence of UV light and apoptosis. Coll Antropol. 2007 Jan;31 Suppl 1:83-5. [abstract]
5. Zhang A, Feng H, Yang G, et al; Unventilated indoor coal-fired stoves in Guizhou province, China: cellular and genetic damage in villagers exposed to arsenic in food and air. Environ Health Perspect. 2007 Apr;115(4):653-8. Epub 2007 Jan 9. [abstract]
6. Rose LC; Recognizing neoplastic skin lesions: a photo guide. Am Fam Physician. 1998 Sep 15;58(4):873-84, 887-8. [abstract]
7. NICE Guidance on Cancer Services; Improving Outcomes for People with Skin Tumours including Melanoma, NICE (Update, May 2010)
8. Referral for suspected cancer, NICE Clinical Guideline (2005)
9. Lansbury L, Leonardi-Bee J, Perkins W, et al; Interventions for non-metastatic squamous cell carcinoma of the skin. Cochrane Database Syst Rev. 2010 Apr 14;(4):CD007869. [abstract]
10. Photodynamic therapy for non-melanoma skin tumours (including premalignant and primary non-metastatic skin lesions), NICE Interventional Procedure Guideline (2006)
11. Meyers AD; Head and Neck Squamous Cell Carcinoma, Medscape, Mar 2011
12. Kibarian MA, Hruza GJ; Nonmelanoma skin cancer. Risks, treatment options, and tips on prevention. Postgrad Med. 1995 Dec;98(6):39-40, 45-8, 55-6 passim. [abstract]

Internet and further reading

• Squamous cell carcinoma of the skin, DermNet NZ

Acknowledgements