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tanning beds confers an increased
risk for melanoma , particularly in younger patients . 10
Clinical and epidemiological evidence suggests that UVR exposure early in life is particularly relevant to the risk of melanoma . Patients who experienced childhood sunburn on five or more occasions have a twofold relative risk of melanoma . 11
It is not fully understood why intense , intermittent UVR exposure
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US National Cancer Institute / bit . ly / 3K6hcl9 |
Box 3 . Phenotypic traits that are risk factors for melanoma
• Light skin phototype .
• Red hair .
• Blue eye colour .
• Freckling .
Box 4 . Indications for hereditary melanoma susceptibility testing
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contributes most significantly to the risk of melanoma , while chronic , suberythemogenic UVR is more strongly associated with keratinocytic skin cancers .
Phenotypic traits
Phenotypic traits that reflect skin sen-
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• Families with three or more relatives with melanoma .
• Individuals with three of more primary melanomas .
• Individuals aged 40 or younger with a diagnosis of melanoma . 19
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sitivity to sunlight are well-recognised |
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risk factors for melanoma ( see box 3 ); these confer a two to fourfold increased risk for melanoma . 12 |
Immunosuppression
Immunosuppressed patients are at
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High naevus count
Some naevi are precursors to mela-
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Figure 1 . Melanoma of the skin . |
increased risk of melanoma . These include organ transplant recipients , patients with lymphoma and those |
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noma ; however , most ( about 75 %) of |
with HIV . 26 |
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melanomas arise as a new and independent lesion with no evidence of an associated naevus . 13 , 14 It is the presence of naevi , particularly in high numbers , that is a marker of overall melanoma risk .
The total count of naevi that confers increased risk of melanoma is generally considered to be at least 50-100 naevi . 15 In these individuals , the associated relative risk of mela-
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Jonathan Trobe , MD / CC BY 3.0 / bit . ly / 3IoBSUl |
PATHOGENESIS
BOTH UVA and UVB radiation are implicated in the pathogenesis of melanoma . It has been proposed that UVB radiation induces direct , melanin-independent DNA damage in melanocytes , while UVA drives pigment-dependent oxidative DNA damage that contributes to the formation of melanoma . 27
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noma has been reported to be at least |
The mitogen-activated protein |
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five , and up to 15 . 16 |
kinase ( MAPK ) pathway and microph- |
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Family history of melanoma
About 10 % of people diagnosed with
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thalmia-associated transcription factor have been identified as having a key role in melanoma pathogenesis . |
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melanoma have a family history of the condition . 17 However , only a minority of these patients will have a true inher- |
MAPKs are involved in directing cellular responses to a diverse array of stimuli , and microphthalmia-associ- |
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ited risk ; it is estimated that fewer than 10 % of melanomas are familial . 17 Similar heavy UVR exposure among family |
ated transcription factor regulates the differentiation and development of melanocytes and retinal pigment epi- |
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members who also share susceptible |
thelium . The MAPK pathway is acti- |
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skin phototypes may account for some |
vated in almost all melanomas , with |
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apparent familial risk . Multiple genes contribute to the predisposition to melanoma . 18 Genetic testing may be warranted |
Figure 2 . Melanoma of the iris . |
different variations associated with particular melanoma subtypes . 28 The most common alterations include BRAF and NRAS in cutaneous and |
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where it is strongly suspected that |
conjunctival melanomas , KIT in acral |
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an inherited mutation is contrib- |
and mucosal melanoma and GNAQ |
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uting to the risk of melanoma in a |
and GNA11 in uveal melanoma . 29-31 |
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family . Box 4 lists the indications |
Characterisation of the MAPK |
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for hereditary melanoma suscepti- |
pathway and BRAF mutations has |
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bility testing in Australia . |
informed the development of targeted |
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Mutations in both tumour sup- |
treatments for patients with meta- |
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pressor genes and oncogenes are |
static melanoma containing the BRAF |
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associated with familial melanoma . |
V600 mutation , which can signifi- |
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Pathogenic variants in the CDKN2A |
cantly prolong survival . |
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gene are the most common cause in cases of familial melanomas . 20
Personal history of melanoma
Patients with a prior history of mel-
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Are atypical / dysplastic naevi melanoma precursors ?
Mutations in BRAF can also occur in
naevi . The mutation burden increases from benign lesions through to mela-
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anoma are at greater risk of further |
nomas , with dysplastic naevi demon- |
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primary melanomas ( both cutaneous and non-cutaneous variants ). 21 The risk of developing a second mela- |
strating an intermediate genetic signature . 32 However , the theory that dysplastic naevi represent precursor |
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noma is highest in the 12 months after |
lesions to melanomas has not been |
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the original diagnosis ; the increased |
proven . While progression from nae- |
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risk persists long-term and these |
vus to melanoma can occur , and has |
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patients are at higher lifelong risk of further melanomas . 22 It has been estimated that the risk of a second melanoma ranges from 2-11 % at five years after initial diagnosis . 22 , 23 This risk is similar for patients with in situ or invasive melanoma . 22
The risk of further primary melanoma may , in part , be dependent on patient factors . Individuals with high naevus counts or a history of
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Figure 3 . Malignant melanoma on the head of an elderly man .
for a second primary lesion . 24 Some research suggests that the age at diagnosis and the site of the initial melanoma may influence future risk . A population-based study showed that patients younger than 30 at
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head or neck , had a greater risk of further primary melanomas , compared with other patients . 25
Age
The incidence of melanoma increases
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The median age at diagnosis is 59 in women and 64 in men . 1 However , it is important to note that melanoma is the most common cancer in young people ( aged 15-29 ) in Australia and should not be considered |
been documented in some lesions , very few dysplastic naevi will develop into melanoma . Studies have shown that naevus-associated melanomas develop at similar rates in common naevi as they do in dysplastic or atypical naevi . 33
DIAGNOSIS
MELANOMA survival is strongly correlated with tumour thick-
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dysplastic naevi are at greater risk |
diagnosis , with melanoma on the |
with advancing age ( see figure 3 ). |
a disease of the ageing . 1 |
ness at diagnosis . Thin , or |
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