Basal cell carcinomas (BCCs) are slow-growing, locally invasive malignant epidermal skin tumours which are thought to arise from hair follicles. The tumour infiltrates local tissues through the slow irregular growth of subclinical finger-like outgrowths and morbidity results from local tissue invasion and destruction, especially on areas of chronic sun exposure, such as the face, head and neck.
Metastasis is relatively rare with a metastasis rate of 0.0028% to 0.5%. However, there is a 2% incidence of metastasis for tumours larger than 3 cm in diameter, 25% for tumours larger than 5 cm and 50% for tumours larger than 10 cm in diameter.
- BCC predominantly affects Caucasians and is very uncommon in dark-skinned races. BCC is the most common cancer in Europe, Australia and the USA and is showing a worldwide increase in incidence.
- An Australian study showed an incidence for superficial BCCs of 336/100,000 men and 251/100,000 women per annum.
- Inconsistent data collection means that accurate figures for the incidence in the UK are difficult to obtain.The reported incidence of BCC in South Wales is 128 per 100,000 for men and 105 per 100,000 for women.
- There is a regional variation in incidence - eg, approximately 120/100,000 in South West England compared with an incidence for the whole of England of approximately 90/100,000 population.
- Superficial BCCs occur at a younger age than other BCC variants, particularly in women.
- The most significant aetiological factors appear to be genetic predisposition and exposure to ultraviolet (UV) radiation.
- The sun-exposed areas of the head and neck are the most commonly involved sites. Sun exposure in childhood may be especially important.
- Increasing age, male sex, skin types I and II (skin that always burns and never/only sometimes tans), immunosuppression and arsenic exposure are other recognised risk factors. A high dietary fat intake may also be relevant.
- People diagnosed with one BCC are at increased risk of developing further BCCs. The risk of developing a second BCC within three years of the first presentation is approximately 44%.
- The incidence rates of BCC increase with age and, over the age of 55, the age-specific incidence rates are higher in males than in females. This gap between males and females increases with age.
- Multiple BCCs are a feature of basal cell naevus (Gorlin's syndrome):
- Autosomal dominant inheritance.
- Multiple BCCs.
- Pitting of the palms and soles.
- Jaw cysts.
- Spine and rib anomalies.
- Calcification of the falx cerebri.
- Other conditions associated with an increased risk of BCC include xeroderma pigmentosa and albinism.
- The sun-exposed areas of the head and neck are the most commonly involved sites.Approximately 80% occur on the head and neck, with the rest mainly on the trunk and lower limbs.
- Early lesions are often small, translucent or pearly and have raised areas with telangiectasia.
- The classic rodent ulcer has an indurated edge and ulcerated centre. It is slow-growing but can spread deeply to cause considerable destruction.
Types of basal cell carcinoma
- Solitary, shiny, red nodule with large telangiectatic vessels.
- Commonly on the face.
- Cystic, pearly, telangiectasia.
- May be ulcerated.
- Micronodular and microcystic types may infiltrate deeply.
- Often multiple, usually on the upper trunk and shoulders. Equal distribution over the face, trunk and limbs, although the site of predilection seems to vary according to sex (the head in women, the trunk in men).
- Erythematous well-demarcated scaly plaques, often larger than 20 mm at presentation. Central clearing and a thread-like border. A rolled edge can be seen if stretched. The lesion may bleed or weep.
- Slow growth over months or years; usually not aggressive, rarely become invasive and extremely rarely metastasise. Less likely to erode and ulcerate than nodular BCCs.
- May be confused with Bowen's disease or inflammatory dermatoses.
- Particularly responsive to medical rather than surgical treatment.
- Also known as sclerosing or infiltrative BCC.
- Usually found in mid-facial sites.
- More aggressive and have poorly defined borders.
- Characterised by thickened yellowish plaques.
- Often present late and may become very large and then require extensive plastic surgical reconstruction. May infiltrate cutaneous nerves (perineural spread).
- Prone to recurrence after treatment.
- Brown, blue or greyish lesion.
- Nodular or superficial histology.
- Seen more often in individuals with dark skin.
- May resemble malignant melanoma.
- Mixed BCC and squamous cell carcinoma (SCC).
- Potentially more aggressive than other forms of BCC.
- Nodular basal cell carcinoma:
- Superficial BCC:
- Pigmented BCC (see separate article Black and Brown Skin Lesions):
- Morphoeic BCC:
- Scar tissue.
- Localised scleroderma.
The National Institute for Health and Care Excellence (NICE) recommends:
- Consider routine referral for people if they have a skin lesion that raises the suspicion of a BCC.
- Only consider a suspected cancer pathway referral (for an appointment within two weeks) for people with a skin lesion that raises the suspicion of a BCC if there is particular concern that a delay may have a significant impact, because of factors such as lesion site or size.
- Investigation is primarily by visual inspection and removal for histology where necessary.
- All excised specimens should be sent for histopathological examination.
- When non-surgical treatments are used, an incisional biopsy must be sent before treatment for confirmation of the diagnosis.
- Biopsy is also indicated when clinical doubt exists or when the histological subtype of BCC may influence treatment selection and prognosis.
- For most patients with non-melanoma skin cancer (NMSC) no formal staging beyond clinical examination for lymphadenopathy is required.
- CT or MRI scan is indicated in cases where bony involvement is suspected or where the tumour may have invaded major nerves, the orbit or the parotid gland.
NICE recommends that low-risk BCCs be managed in primary care as long as the GP meets the requirements to perform skin surgery within the framework of the Direct Enhanced Services and Local Enhanced Services. There should be no diagnostic uncertainty that the lesion is a primary nodular low-risk BCC and meets the following criteria:
- The patient is not:
- Aged 24 years or younger (that is, a child or young adult).
- Immunosuppressed or has Gorlin's syndrome.
- The lesion:
- Is located below the clavicle (that is, not on the head or neck).
- Is less than 1 cm in diameter with clearly defined margins.
- Is not a recurrent BCC following incomplete excision.
- Is not a persistent BCC that has been incompletely excised according to histology.
- Is not morphoeic, infiltrative or basosquamous in appearance.
- Is not located:
- Over important underlying anatomical structures (for example, major vessels or nerves).
- In an area where primary surgical closure may be difficult (for example, on digits or the front of the shin).
- In an area where difficult excision may lead to a poor cosmetic result.
- At another highly visible anatomical site (for example, the anterior chest or shoulders) where a good cosmetic result is important to the patient.
If the BCC does not meet the above criteria, or there is any diagnostic doubt, following discussion with the patient they should be referred to a member of the local hospital skin cancer multidisciplinary team (LSMDT).
If the lesion is thought to be a superficial BCC, the GP should ensure that the patient is offered the full range of medical treatments (eg, photodynamic therapy (PDT)) and this may require referral to a member of the LSMDT. Incompletely excised BCCs should be discussed with a member of the LSMDT.
Surgery and radiotherapy appear to be the most effective treatments, with surgery showing the lowest failure rates. There is only limited evidence of the effectiveness of other treatment modalities compared with surgery.Recurrent BCC is more difficult to cure than primary lesions.
- Excision with primary closure, flaps and grafts: an excision margin of 4 mm around the tumour is recommended where possible, especially for all high-risk BCCs.
- Tumours which have been incompletely excised, especially high-risk BCC and lesions incompletely excised at the deep margin are at high risk of recurrence and should be re-excised.
- Mohs' micrographic surgery:
- Excision of the BCC 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, especially for recurrent and high-risk aggressive growth pattern BCCs such as morphoeic BCCs.
- High-risk and recurrent tumours are best treated by Mohs' micrographic surgery where this is available.
- Overall cure rates for primary BCC are almost 100% and 95% for recurrent BCC.
- The main problems are the length of the procedure, the need for special equipment and training, the relatively high cost and the limited availability in the UK.
- A Cochrane review found that no reliable conclusions could be made as to whether Mohs' micrographic surgery or surgical excision resulted in a lower recurrence or complication rate for periocular BCC.
Curettage and cautery/electrodesiccation
- Not recommended for recurrent, large, morphoeic tumours or tumours on the face.
- The overall cure rate is over 90% for low-risk BCCs.
- Performed using a curette to remove soft material from the tumour.
- The base of the tumour is then destroyed, using either hyfrecation or cautery.
- Curettage and cautery is a good treatment for low-risk BCC.
- The histology may be difficult to interpret, as the lesion may be incompletely removed and margins of excision cannot be assessed optimally.
- The evidence on the safety of electrochemotherapy for primary BCC has raised no major concerns. However, the evidence on its efficacy is limited in quantity and quality.
- Cryotherapy is well established for treating small low-risk lesions, including superficial BCCs.Histology is not available unless an incisional biopsy is taken first.
- Topical treatment:
- Imiquimod 5% cream:
- Topical Imiquimod appears to be effective in the treatment of primary small superficial BCCs.
- Is an immune response-modifying agent that has been licensed for the treatment of small superficial BCCs.
- Imiquimod has been shown to achieve clearance rates ranging from 70% to 100% but relapse rates appear higher than with other, conventional treatments and there are some difficulties with side-effects (eg, pruritus).
- More effective for superficial than for nodular tumours.
- Topical fluorouracil 5% cream is useful in the management of multiple superficial BCC on the trunk and limbs. Cure rates are in the region of 80%.
- Imiquimod 5% cream:
- PDT appears to be effective for the treatment of superficial BCC and nodular BCC.
- Involves the use of light therapy in combination with a topical photosensitising agent to destroy cancer cells.
- Its use has been well described in the treatment of superficial BCC. Evidence of efficacy is adequate to support its use.
- The average clearance rate for superficial BCC is about 85% but is lower in nodular BCC.
- Advantages of PDT include a low rate of adverse effects and a good cosmetic outcome.
- The disadvantages are that the patient has to be available for a period of at least 3-4 hours for treatment, and that the photosensitiser and equipment are relatively expensive.
- There is currently little information available on long-term cure rates.
- The best indications for radiotherapy are BCC with incomplete excision, recurrent BCC, nodular BCC of the head and neck under 2 cm and BCC with invasion of bone or cartilage.
- Useful treatment for patients with NMSC 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, especially for young patients, is worse than for other treatments.
- The same area cannot be treated twice and so surgery is required for any recurrence.
- Radiotherapy can also be used in cases when the margins of excision appear to be incomplete on histopathological examination.
- It should not be used to treat patients with Gorlin's syndrome because of the carcinogenic potential of low-dose irradiation at the margins of the treated areas.
Sometimes, especially in the very elderly and debilitated, it may be appropriate to provide no treatment (given the slow growth and low risk of many superficial BCCs) or palliative (debulking or radiotherapy) treatment if the tumour is symptomatic.
Dr Hayley Willacy draws your attention to a study that was released at the British Association of Dermatologists’ Annual Conference - July 2017. The researchers issued a warning about the dangers of using unlabelled herbal treatments, after potent steroids were detected in samples of several such products. The dangers of these products are two-fold - firstly that it is claimed that they treat a disease which they don't, leaving it unchecked, and secondly that they are poorly labelled, and often contain ingredients that should only be used on advice from a doctor.
- Mortality is low because BCCs rarely metastasise.
- Recurrent tumours have poorer cure rates than primary tumours.
- Following development of a BCC, patients are at significantly increased risk of developing subsequent BCCs at other sites.
- High-risk groups for the development of further BCC include patients with truncal BCC and those presenting with tumour clusters.
- Patients with BCC also have an increased risk of developing SCC and malignant melanoma.
- There may also be a small increased risk of other malignancies, such as cancer of the lung, thyroid, mouth, breast and cervix and also non-Hodgkin's lymphoma.
- Education on sun avoidance:
- Avoid UV exposure in susceptible individuals, particularly children and adolescents.
- Stay out of the sun between 10 am and 4 pm.
- Use high-factor sunscreens.
- Wear wide-brimmed hats, long-sleeved shirts and trousers.
- Education of patients to seek early assessment if further lesions develop. Earlier treatment is more effective.
- Oral retinoid treatment may prevent or delay the development of new BCCs.
Further reading and references
; DermIS (Dermatology Information System)
; DermIS (Dermatology Information System)
; British Association of Dermatologists (2008)
; Metastatic Basal cell carcinoma: a case report and review of the literature. Eplasty. 2011 Apr 2911:ic8.
; Basal cell carcinoma: histological classification and body-site distribution. Br J Dermatol. 2006 Aug155(2):401-7.
; European Dermatology Forum (2012)
; NICE Guidance (May 2010 update)
; Basal cell carcinoma. BMJ. 2003 Oct 4327(7418):794-8.
; Variations of basal cell carcinomas according to gender, age, location and histopathological subtype. Br J Dermatol. 2002 Jul147(1):41-7.
; DermIS (Dermatology Information System)
; National Cancer Institute (USA)
; NICE Clinical Guideline (2015 - last updated July 2017)
; Interventions for basal cell carcinoma of the skin. Cochrane Database Syst Rev. 2007 Jan 24(1):CD003412.
; Mohs micrographic surgery versus surgical excision for periocular basal cell carcinoma. Cochrane Database Syst Rev. 2014 Dec 1212:CD007041. doi: 10.1002/14651858.CD007041.pub4.
; NICE Interventional Procedure Guidance, February 2014
; Imiquimod: new indication. Basal cell carcinoma: inferior to other treatments. Prescrire Int. 2006 Aug15(84):130-1.
; NICE Interventional Procedure Guidance, February 2006
; S.A. Chan and D.A. Thompson, Birmingham Skin Centre, Birmingham, U.K. (2017)
; Genetics and risk factors for basal cell carcinoma. Br J Dermatol. 2006 May154 Suppl 1:5-7.
Cancer is no doubt a pretty complex disease, so it's obvious that it is going to require a pretty complex cure, but how would this cure be? Would it be nanobots, a machine capable of somehow...michael51065
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