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Mladeži u dečjem uzrastu: dogma i fakat

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.

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Mladeži u dečjem uzrastu: dogma i fakat

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  1. Mladeži u dečjem uzrastu: dogma i fakat Marko B. Lens, MD PhD FRCS

  2. 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

  3. Naevi and age Heterogeneity between naevi induction and involution processes

  4. Melanocytic naevi Junctional Compound Intradermal

  5. 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)

  6. 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)

  7. Atypical mole syndrome • 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

  8. Naevi • 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

  9. 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.

  10. Recreational sun exposure and melanoma at different sites

  11. Figure 1 Naevus counts equal or above 50 and risk of melanoma

  12. Risk of melanoma in relation to naevi above 5 mm in diameter

  13. 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

  14. Managing uncertainty: cannot identify lesion Correct Diagnosis Correct Management No Diagnosis Incorrect Management Avoid removing any lesion where you are uncertain of the diagnosis

  15. Diagnosis improved with dermatoscopy

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  18. 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

  19. 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

  20. Management: Basic Principles • Send everything for histological examination • See and understand the histology report • Know how to manage the histology report

  21. Melanocytic skin lesions: Dermatological techniques • Ellipse excision • Curettage &cautery • Shave excision

  22. Pyogenic granuloma ??? • Urgent surgery • Histology • Amelanotic melanoma

  23. Melanoma in children • Melanoma in children is rare • Only 0.3% to 0.4% of all melanomas occur in prepubertal 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

  24. 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.

  25. Age Specific Melanoma Incidence and Mortality by Gender

  26. Risk of melanoma and family history • 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)

  27. Melanoma and germline mutations 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

  28. Genes et Naevus • 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?

  29. Naevus and ageing • 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?

  30. Telomeres • 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

  31. Telomere length in relation to naevus counts

  32. Theory of antagonistic pleiotropy • p53 (“Guardian of the genome”) • Skin cancerogenisis Versus skin ageing (cell senescence)

  33. Naevus marker of reduced senescence • 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

  34. Vit D and sun exposure • 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

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