CLINICAL REVIEW: Non-Melanoma and Pre-Skin Cancers

The essentials

* Skin malignancies are the commonest and most preventable of cancers.

* Atypical naevus syndrome has a 15 times higher risk of melanoma.

* Basal cell carcinomas are the commonest malignant neoplasm in humans.

* Squamous cell carcinomas can metastasise by lymphatic spread.

* Sun beds emit ultraviolet radiation and cannot be used without risk.

1. Epidemiology of demwtotogical malignancies

Skin malignancies are the most common and the most preventable of all the cancers. About 15 per cent of all GP consultations relate to skin problems, and commonly include atopic eczema, acne and venous leg ulcers, but especially skin cancers and pre-cancers, melanomas and suspicious moles.

Malignant melanoma was dealt with in depth in a recent Clinical Review (GP, 4 March). Copies can be downloaded at GPonline.com.

Incidence of non-melanoma skin cancers

There are at least 40,000 new cases of nonmelanoma skin cancers in the UK each year, and the numbers of cases are doubling every decade. Increasing foreign travel to sunny climates, sunbathing and depletion of the ozone layer mean an increase in exposure to ultraviolet radiation from the sun, the main causative agent. These factors, and the increasing numbers of older people, are contributing to this remarkable rise.

Early recognition and management of a number of pre-cancerous skin conditions could reduce the overall incidence of frank disease.

Actinic or solar keratoses

About 25 per cent of people over the age of 60 in the UK will have at least one actinic keratosis. The chance of transformation to squamous cell carcinoma is less than 1 per cent, but the number of lesions and their site act as an indicator of sun exposure and are a risk factor for skin cancer.

They appear as areas of red, rough skin on exposed sites such as the scalp, forehead and back of the hands, and can be painful. They have a characteristic rough texture.

Males are affected twice as much as women, and numbers increase with age. Risk factors include living at high altitudes, in the tropics, and working outdoors. Caucasian fair skin and immunosuppressant therapy also increase the risk.

Prevention includes sun avoidance and sun protection.

Topical therapy involves the use of creams such as 5% 5- fluorouracil, diclofenac sodium, retinoids and salicylic acid. Cryotherapy, curettage and cautery, ellipse excision and photodynamic therapy are effective, and systemic treatment with retinoids can also be used.

Six-monthly follow-up is suggested in case of evolution towards squamous cell carcinoma (SCC). About 25 per cent of solar keratoses resolve by themselves after 12 months’ regular use of sun-screens and avoidance of ultraviolet light.

Bowen’s disease

Bowen’s disease, or intraepidermal carcinoma in situ produces fixed, flat, red and sometimes scaly patches. These are particularly found on the legs and trunk.

Bowen’s disease usually progresses slowly to invasive SCC. It is necessary to treat all such lesions. Referral to confirm the diagnosis is advisable. Treatments include 5-fluorouracil cream, cryotherapy, curettage and photodynamic therapy.

Actinie keratosis: one quarter of people over the age of 60 will have at least one such lesion present

Key points

* There are at least 40,000 new cases of nonmelanoma skin cancers in the UK each year.

* About 25 per cent of people over 60 years have at least one actinic keratosis.

* About 25 per cent of actinic keratoses resolve by themselves if appropriate advice is followed.

* Bowen’s disease usually progresses slowly to invasive squamous cell carcinoma.

2. Other pre-cancerous conditions

Atypical naevus syndrome

The atypical naevus syndrome is characterised by many and varied naevi.They usually vary in shape, size, colour, edge and pattern of pigmentation.

Often there are 100 or more naevi, and frequently there is at least one naevus 8mm or larger in diameter. The syndrome can occur sporadically or in families.

An atypical naevus is often 5mm or more in diameter, usually with irregular, fuzzy borders. Most lesions are flat. Some have a central papule surrounded by a macular pigmented rim, creating a ‘fried- egg’ appearance, and they have variegated shades of tan and brown. They are most common on the trunk, especially on the upper back. Some of the clinically atypical naevi are dysplastic on histology.

These patients have approximately a 15 times higher risk of developing malignant melanoma than the general population. Moles should be checked and investigated if there is any change in size, shape or colour, inflammation, ooze, bleeding or itching, or if they are larger than 7mm.

Keratoacanthoma

Keratoacanthomas are rapidly growing epidermal tumours that are thought to arise from the hair follicles. They can be regarded as self-healing SCCs and appear as symmetrical keratotic papules or nodules with a thickened base.

Left alone, most will spontaneously involute. However, occasionally they progress to an invasive SCC, so need to be observed.

Basal cell naevus syndrome

Basal cell naevus syndrome (Gorlin’s syndrome) is a rare autosomally dominant inherited disorder with wide-set eyes, saddle nose, frontal bossing, prognathism (prominent chin), and skeletal abnormalities. Skin manifestations include pits in the palms and soles, and numerous basal cell carcinomas.

Organoid naevi

The organoid naevus (naevus sebaceous of Jedassahn) represents an area of defective embryogenesis of the pilosebaceous-apocrine unit. It appears at birth, or soon after, as an area of alopecia. Hyperplasia and/or tumours appear around the time of puberty.

Patients often present at a very young age with yellow plaques on the skin. These then become hyperpigmented verrucous papules in which basal cell carcinomas (BCCs) can later develop.

Xeroderma pigmentosum

Xeroderma pigmentosum is a rare disorder transmitted in an autosomal recessive manner. It is characterised by photosensitivity, pigmentary changes, premature skin ageing and malignant tumour development, due to a cellular hypersensitivity to ultraviolet radiation resulting from a defect in the normal DNA repair mechanism.

Mortality is common from metastatic malignant melanoma and SCC.

Patients younger than 20 years have a 1,000-fold increase in incidence of melanoma and nonmelanoma skin cancer.

Kerataacanthoma: most will involute spontaneously

Key points

* Atypical naevus syndrome patients have 100 ormorenaevi.

* Keratoacanthomas occasionally develop into SCCs.

* Xeroderma pigmentosum is a rare disorder characterised by abnormal skin ageing and sensitivity to ultraviolet light.

3. Basal cell carcinomas

Basal cell carcinomas (BCCs) are the commonest malignant neoplasm in humans. If treated correctly, they are also the most curable, but if neglected can be fatal.

BCCs are slow-growing locally invasive malignant epidermal tumours affecting mainly Caucasians.The commonest cause is chronic sun exposure, so are usually found on sun-exposed sites. Metastases are extremely\are, and the main problem is local invasion of tissue that can be destructive and disfiguring.

The classic feature is the raised pearly edge, but they may also be nodular, cystic, ulcerated (rodent ulcer), superficial, morphoeic, keratotic or pigmented. Sometimes diagnosis can only be confirmed by histology. A dermoscope (dermoscope review,page 55) can be a useful aid to diagnosis.

Risk factors include increasing age, male sex, sun exposure, fair white skin that burns easily, a family history and immunodeficiency. Ionising radiation can cause BCCs 15-20 years after exposure. Other factors include a history of exposure to arsenic, coal, industrial tar or paraffin, Gorlin’s syndrome and xeroderma pigmentosum.

If a patient has one BCC, there is a 40 per cent chance of another occurring within three years.

Prognostic factors include tumours more than 2cm across, site, type and margins, histological subtype, previous treatments and being immunocompromised.

Surgical treatment

Surgical options include curettage and cautery. Electrodesiccation is the best treatment for most BCCs. It is especially suitable for small, well defined, primary lesions with non-aggressive histology, when there is a 97 per cent cure rate. Cryosurgery is possible for low-risk BCCs.

Excision of primary BCCs is effective. Combined with curettage before excision, it allows for a more accurate assessment of the margin and can increase cure rate. Recurrent BCCs are more difficult. Mohs’ micrographie surgery can improve cure of recurrent BCCs but is time-consuming, and involves microscopic assessment of samples of the area of excision to ensure adequate margins.

Radiotherapy has good cure rates, but has the problem of accurately of assessing tumour margins. It requires a clinical oncologist and several visits to the radiotherapy department, which can be difficult and worrying for the elderly.

Topical therapy with 5-fluorouracil can be useful for multiple low-risk superficial extrafacial BCCs. Imiquimod is a new agent that may gain a place in treatment.

All BCC patients should have an annual skin examination.

Destructive BCC of the ear: these carcinomas are slow-growing but if left untreated can be disfiguring

Key points

* The commonest cause of BCCs is chronic sun exposure.

* BCCs present with awide range of clinical features, so diagnosis may be difficult.

* Small, well defined, primary lesions have a cure rate of up to 97 per cent.

* Topical therapy can be useful in multiple superficial non- facial BCCs.

4. Squamous cell carcinomas

SCCs are invasive malignant tumours that have the potential to metastasize, tending to spread by lymphatics.They arise from the keratinising cells of the epidermis or its appendages, and are the second most common skin cancers. SCCs are also caused by chronic sun exposure and affect the fairer skinned.

They appear as non-healing, slowly growing lesions with significant induration on palpation and typically crust or ulcerate.

Risk factors

Risk factors for SCCs are similar to those for BCCs, with males affected twice as much as females. Fair skin, xeroderma pigmentosum and exposure to previous ionising radiation or arsenic are other risk factors.

SCCs can also occur in chronic wounds, scars, burns, and ulcers, and may develop from Bowen’s disease or solar keratoses. Immunodeficiency increases the risk, and there is a small association with HPV. SCCs are more common in the elderly.

SCCs in sun-exposed sites carry a better prognosis than those in non-exposed sites. A worse prognosis occurs with lesions in areas of radiation or thermal injury, or in chronic ulcers or Bowen’s disease.

Lesions greater than 2cm diameter or depth of over 4mm are twice as likely to recur locally and three times as likely to metastasise.The degree of differentiation is also relevant.

The success of curettage and cautery and cryosurgery depend on the experience of the physician, and first-choice treatment may be surgical excision, including Mobs’ micrographie surgery. Radiotherapy is sometimes used for better cosmetic and functional results, such as in lesions on the lip and in advanced tumours.

Metastatic SCCs

Metastatic SCCs require a multi-disciplinary team, and the degree of spread must be established. If there is enlargement of lymph nodes, then fine-needle aspiration or excision biopsy should be performed and, if positive, followed by a regional node dissection. In the absence of lymph node enlargement with a high-risk tumour, high-resolution ultrasound-guided fine needle aspiration cytology may be useful.

About 95 per cent of recurrences and metastases occur within five years, so patients are generally kept under observation for this time.

SCCs are slow-growing and typically crust or ulcerate

Key points

* SCCs appear as non-healing, slowly growing, indurated lesions with ulceration,

* SCCs can occur in chronic wounds, scars, burns, and ulcers.

* Radiotherapy is sometimes used to give better cosmetic and functional results.

* Metastatic SCCs require involvement of a multi-disciplinary team.

5. Patient education and monitoring

UVB and UVA are responsible for skin ageing and skin malignancy. They both also cause redness and sunburn. Sun beds emit ultraviolet radiation and cannot be used without risk.

Patient education and prevention

Patient education and prevention strategies are currently in a state of flux. The chairman of the skin Cancer Prevention Working Party has voiced concerns that ‘there is no such thing as a healthy tan’. This is leading people to avoid the sun completely, and recent evidence suggests that lack of sunlight can lead to vitamin D deficiencies and cause an increase in osteoporosis, prostate cancer and autoimmune disease.

Campaigns such as SunSmart from Cancer UK and Sunsafe (the DoH’s skin cancer prevention campaign) offer helpful advice, but there are concerns about undue dependence on sunscreens because they may encourage excessive exposure. Sunburn in children under 15 years is a major risk factor, and outdoor occupations are also a greater risk. Constant reinforcement of advice to limit exposure is needed.

Monitoring

Total skin examination is the best method of detecting skin malignancy. It can be agreed that annual total skin examination should be practiced in at-risk people such as those with a history of any type of skin cancer, or the atypical naevus syndrome.

Mole mapping is a newer monitoring method for the atypical naevus syndrome, involving whole-body, high-resolution medical photography. Existing moles can be recorded at a specific reference point. Future comparisons allow early detection of subtle changes in size, shape and colour, or any new moles. However, molemapping does not check for SCCs or BCCs.

Computerised dermoscopy provides a closeup image into a mole allowing the layers of skin beneath the surface to be seen. A computer then generates a risk analysis of the likelihood of melanoma.

Computerised dermoscopy helps in monitoring

Key points

* The skin Cancer Prevention Working Party has voiced concerns that ‘there is no such thing as a healthy tan’.

* Campaigns such as SunSmart from Cancer UK and Sunsafe (the DoH’s skin cancer prevention campaign) offer helpful advice.

* Mole mapping is a newer monitoring method for the atypical naevus syndrome.

Further resources

Further reading

Differential Diagnosis in Dermatology by Richard Ashton and Barbara Coppard, by Radcliffe Publishing.

Previously in Clinical Review

You can produce your own re-prints of Clinical Reviews published in the past year by logging on to GPonline.com. Recent issues have covered the following conditions:

* Autism (13 May)

* Acne (6 May)

* Heart failure (29 April)

Contributed by Dr Jane Barnard, a GP with a special interest in dermatology in Yateley, Hampshire, and Dr Christopher Rowland Payne, consultant dermatologist at The London Clinic

Copyright Haymarket Business Publications Ltd. May 20, 2005