Despite its increased incidence, melanoma remains relatively rare in the UK, with reported crude incidence rates of about 15 per 100,000 of the population. Mass screening is therefore not cost-effective and effort should be targeted towards identifying patients at increased risk.
Phenotypic risk factors for melanoma include fair skin, the presence of freckles, red or blonde hair and green or blue eyes.1 However, these are common in the general population and the associated RR is only of the order of two to three times greater.
More significant risk factors are large numbers of benign melanocytic naevi,2 multiple atypical naevi and sporadic or familial atypical mole syndrome. These patients may benefit from surveillance, which can detect melanoma earlier.
The significance of mole numbers
Total body mole counts of white patients with no family or personal history of melanoma have shown that the mean number of moles rises rapidly in the second decade of life and peaks in the third decade.3
Naevi regress with time, so that by the eighth decade, the numbers are similar to those seen in prepubertal children. The counts are persistently higher in females compared with males. Several studies have shown that the risk of melanoma is directly related to the number of benign naevi.2,4,5
One study showed that dividing subjects into groups with 10, 50 and 100 naevi was a useful means of melanoma risk assessment, the risk approximately doubling with each increase.6 Site-specific mole counts (on limb or trunk) are also associated with a high risk of melanoma, and mole count at one site of the body correlates with the total mole count.7,8
Researchers have found that asking patients in primary care to count trunk moles could be a feasible way of identifying patients at high risk of developing melanoma.9 However, even if screening in the UK were restricted to individuals with more than 100 benign naevi, it would still be necessary to examine approximately 650 patients to detect one melanoma.
The risk of melanoma is also strongly related to the presence of clinically atypical naevi, particularly if multiple.10-13 Atypical naevi are usually flat, larger than average and have ill-defined blurred margins, variable pigment and, sometimes, an irregular shape (figure 1). Small numbers occur in approximately 10 per cent of the population, but a useful breakpoint for significant increased risk of melanoma is five or more. A personal or family history of melanoma further increases risk, the latter being the stronger risk factor.14
Not all clinically atypical naevi will be histologically ‘dysplastic’, but the more clinically atypical the naevi, the more likely they are to show histological atypia. Atypical naevi may remain unchanged or even regress over time, but a small proportion may progress to melanoma. They are therefore not only a marker of increased risk of melanoma, but also potential precursor lesions.
Atypical mole syndrome
Atypical mole syndrome (AMS) is a clinical diagnosis typified by excess numbers of naevi (usually 100 or more) that are atypical in appearance and have an abnormal distribution (buttocks, ears, hands, feet and scalp).15
Increased numbers of banal naevi have usually appeared by the age of five to 10 years. Slightly pink, larger naevi appear later, particularly on the scalp, and are most easily found on the anterior scalp margin. The phenotype is usually fully established by the age of 20. The tendency to produce naevi is exaggerated, so new naevi continue to develop until late in life.
AMS may occur sporadically in one individual or in an autosomal-dominant fashion within the family. A scoring system has been proposed to define the phenotype (see box 1),16 a score of three or more indicating the presence of AMS. In the UK, about 2 per cent of the normal population are reported to have AMS.16 These patients develop melanomas at a young age and are at increased risk of multiple primaries.
Melanoma risk depends mainly on a personal and/or family history of melanoma and on this basis researchers have defined four groups demonstrating the variability in risk (see box 2).17
Eight to 10 per cent of newly diagnosed patients will report a first-degree relative with melanoma and this confers about a twofold increased risk of melanoma. Hereditary melanoma is defined as a family in which two first-degree relatives are diagnosed with melanoma or families with three or more melanoma patients, irrespective of relationship.
The risk of melanoma is significantly increased in these families, so it is important to identify them, although familial melanoma is rare, accounting for only 1 per cent of cases. Patients with familial melanoma have a lower mean age at diagnosis and a greater tendency to develop multiple primaries; most have atypical naevi.
The major susceptibility genes for familial melanoma are the tumour suppressor gene CDKN2A and more rarely, the oncogene CDK4.18 The probability of identifying a mutation in these genes is less than 5 per cent in families with two affected first-degree relatives, but is of the order of 20 per cent if there are three or more, rising to 60 per cent if six or more relatives are affected. In patients who develop multiple primary melanomas, the probability of finding a mutation is 10-15 per cent.
Surveillance and follow-up
Photographic surveillance has proved invaluable for monitoring patients with multiple naevi.19 More recently, dermoscopic assessment and follow-up of naevi has increased in popularity. In Australia, it has been shown that GPs can improve their diagnosis of melanoma using dermoscopy after a short training period,20 although at least initially, dermoscopy can lead to an increase in the number of excisions of benign naevi.
Dermoscopic images can also be digitally recorded and stored for future comparison, and sequential dermoscopic imaging has proved effective in detecting very early melanomas before clinical changes become obvious.21
Primary care is an excellent setting for opportunistic screening and identification of high-risk patients because up to 90 per cent of people will consult their GP over a two-year period.
A useful approach is to take a rough count of the number of naevi and to note the presence and numbers of any clinically atypical naevi. If there is a high naevus count, look for any atypical distribution and if the AMS phenotype is suspected, calculate likelihood using the AMS scoring system. Finally, take a personal and family history of melanoma.
High-risk groups should be educated about the signs and symptoms of melanoma and given advice about sun protection measures. They should also be encouraged to examine their naevi at regular intervals and report any suspected change.
Those deemed to be very high risk should be offered regular surveillance. If familial melanoma is suspected, consider referral for a dermatological opinion and screening of family members.
|Dr Joy Osborne is an associate specialist in dermatology at Leicester Royal Infirmary. Competing interests: None declared.|
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Originally published in the March 2009 edition of MIMS Oncology & Palliative Care.