Transcript Mladezi u decjem uzrastu: savremen pristup dijagnostici i lecenju

Mladeži u dečjem uzrastu:
dogma i fakat
Marko B. Lens, MD PhD FRCS
Naevi (Moles)
• Melanocytic lesions of the skin
• Children may present a variable spectrum of
melanocytic skin lesions and the great majority
of them is benign.
• Naevi can be congenital or acquired developing
in childhood and early adulthood
• New lesions rare after age of 30 to 35, unless
belong to very moley family
• Naeviinvolutes with age
Naevi and age
Heterogeneity between naevi induction and involution processes
Melanocytic naevi
Junctional
Compound
Intradermal
Other types of melanocytic
naevi
• Dysplastc inaevus (nevus of Clark):
usually a compound nevus with cellular
and architectural dysplasia. Larger then
normal moles and tend to have irregular
colour and borders.
• Blue naevus
• Spitz naevus – a distinct variant of
intradermal nevus, usually in a child. They
are raised and reddish (non-pigmented)
Other types of melanocytic
naevi
• Giant hairy naevus
(with an associated lifetime risk of
melanoma in 4%-10% of patients)
• Naevus of Ito and Naevus of Ota
(congenital, flat brownish lesions on the
face or shoulder)
Atypical mole syndrome
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More than 100 naevi
Naevi on breasts, buttocks, fingers, feet, scalp
Affects 2% of normal population
10 to 20 time increased risk of melanoma
Up to 15% of melanoma cases
Refer to a dermatologist
No need to excise lesions for the purpose of
confirming dysplasia or as a prophylaxis
Naevi
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Strongest risk factor for melanoma
Odds ratios between 2 to 20
Stable risk across all continents despite different UV
exposure
Atypical naevi significant risk factor for melanoma
Site also important. Legs for females and trunk for
males
50 to 60% of all melanomas grow from a mole but also
can appear on normal skin with no pre-existing mole
Sun and melanocytic naevi
(MN)
• Total sun exposure and tendency to burn are
independent risk factors for MN incidence.
• Lifetime number of sunburns and the severity of
sunburns are significantly related to the presence of
largeacquired MN.
• Reducing the total number of hoursof sun exposure is
particularly relevant in sun-sensitive childrenand may
restrain the development of MN, whereas avoiding
sunburnin young children might prevent large MN,
subsequently reducingthe risk of melanoma.
Recreational sun exposure and melanoma at different sites
Naevus counts equal or above 50 and risk of melanoma
Risk of melanoma in relation to naevi above 5 mm in diameter
Suspicious naevi
• Change in weeks or months
• Not years
• Irregular in colour and/or shape with recent
change
• Bleeding and crusting lately
• Itching not very specific
• Geographical border
• Regression (blueish/grey veil)
• The “odd” one out
Managing uncertainty: cannot identify lesion
Correct
Diagnosis
No Diagnosis
Correct
Management
Incorrect
Management
Avoid removing any lesion where you are uncertain
of the diagnosis
Diagnosis improved with
dermatoscopy
75
76
Management of naevi
 Does it need removing?
 Can you reassure the patient?
 Should you remove it?
 Can you remove it?
 Consider site, size, experience & patient
Management of naevi: Basic principles
 Not everything needs to be removed
 Diagnosis and reassurance may be enough
 Stable and unchanging, reassure
 Draw & measure lesion, review after 6-12
weeks
 Advise patient to return if any change
 Time as a diagnostic tool
Management: Basic Principles
 Send everything for histological
examination
 See and understand the histology report
 Know how to manage the histology report
Melanocytic skin lesions:
Dermatological techniques
 Ellipse excision
 Curettage &cautery
 Shave excision
Pyogenic granuloma ???
 Urgent surgery
 Histology
 Amelanotic melanoma
Melanoma in children
 Melanoma in children is rare
 Only 0.3% to 0.4% of all melanomas occur in prepubertal
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age
1.3% to 2% occur in patients younger than 20 years
The incidence of MM in children is estimated to be 0.7 per
million per year in children aged 0 to 9 years, whereas it is
13.2 per million per year in people aged between 15 and 19
years
This incidence is continuing to rise.
Recent data suggest an increasing incidence even in young
age
Pediatric melanoma Versus Adult
melanoma
 Lymph node metastases were more prevalent in
young patients with melanoma compared with
adult (thickness-matched) control patients
 5- and 10-year survival rates were similar.
 Higher percentage of young melanoma patients
have positive family histories and have atypical
nevi suggest that a stronger predisposing genetic
component may be operant in this group.
Age Specific Melanoma Incidence and
Mortality by Gender
Rate per 100,000
120
100
80
M mort
F mort
M inc
F inc
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40
20
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Age
50
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Risk of melanoma and family history
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Familial clustering of melanoma occur in around 1% of
melanoma cases
One parent affected:
RR 2.40(2.10-2.72)
One sibling affected:
RR 2.98(2.54-3.47)
One parent plus one sibling:
RR 8.92(4.25-15.31)
One parent multiple MMs:
RR 61.78( 5.82-227)
Melanoma and germline mutations
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CDKN2A the most common gene altered in
melanoma families
Can affect the p16 and the p14 protein
CDK4 mutations are rare
CDKN2A accounts for up to 25% of melanoma
families
p16 involved in cell cycle and senescence
Genes et Naevus
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60% of the variation in naevus number is determined
by genetic factors
Twin studies. St Thomas. More than 2000 twins
Why is there such a great variation in naevi number in
Caucasian populations?
Why do genes disappear with age?
Naevus and ageing
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It had been noted in our research in familial
melanoma that patients with multiple atypical
naevi were less likely to have sun damage
Less wrinkles, less solar lentigines and fewer
solar keratoses
What is the significance of this?
Telomeres
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Telomeres-DNA sequence at the end of
telomeres
Non coding DNA
Biological clock which shortens with age
The speed of telomere shortening with age
varies between individuals which is in part
genetically determined
Smoking, obesity and chronic diseases can
shorten telomere further
Telomere length in relation to
naevus counts
Age adjusted Trf length
7.3
7.25
7.2
7.15
7.1
7.05
7
6.95
0 - 25
26 - 50
51 - 100
Naevus count
> 100
Theory of antagonistic pleiotropy
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p53 (“Guardian of the genome”)
Skin cancerogenisis Versus skin ageing (cell
senescence)
Naevus marker of reduced
senescence
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Naevus may therefore be a good marker of reduced
ageing
This may be relevant for tissues other than skin and we
are now looking at bones and other tissues
This may explain why large number of naevi has
remained such a common trait in the normal
population
May provide a survival advantage in the selective gene
pool
Vit D and sun exposure
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Is Vitamin D deficiency relevant?
Vitamin D protects against osteoporosis, cancer,
inflammatory and autoimmune disorders
1400 Caucasian females: 10% had Vit D serum levels
below 30 nmol/L
Skin type 1 and 2 more prone to Vit D deficiency
Vitamin D may also increase melanoma survival
Need to be more cautious when recommending sun
avoidance