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

3. 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

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

5. Junctional Compound Intradermal Melanocytic naevi

6. 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)

7. 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)

8. 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

10. Naevi Strongest risk factor for melanoma Strongest risk factor for melanoma Odds ratios between 2 to 20 Odds ratios between 2 to 20 Stable risk across all continents despite different UV exposure Stable risk across all continents despite different UV exposure Atypical naevi significant risk factor for melanoma Atypical naevi significant risk factor for melanoma Site also important. Legs for females and trunk for males 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 50 to 60% of all melanomas grow from a mole but also can appear on normal skin with no pre-existing mole

11. 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.

12. Recreational sun exposure and melanoma at different sites

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

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

15. 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

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

17. Diagnosis improved with dermatoscopy

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20. 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

21. 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

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

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

24. Pyogenic granuloma ??? Urgent surgery Histology Amelanotic melanoma

25. 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

26. 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.

27. Age Specific Melanoma Incidence and Mortality by Gender

28. Risk of melanoma and family history Familial clustering of melanoma occur in around 1% of melanoma cases Familial clustering of melanoma occur in around 1% of melanoma cases One parent affected: RR 2.40(2.10-2.72) One parent affected: RR 2.40(2.10-2.72) One sibling affected: RR 2.98(2.54-3.47) One sibling affected: RR 2.98(2.54-3.47) One parent plus one sibling: RR 8.92(4.25-15.31) One parent plus one sibling: RR 8.92(4.25-15.31) One parent multiple MMs: RR 61.78( 5.82-227) One parent multiple MMs: RR 61.78( 5.82-227)

29. Melanoma and germline mutations CDKN2A the most common gene altered in melanoma families Can affect the p16 and the p14 protein Can affect the p16 and the p14 protein CDK4 mutations are rare CDK4 mutations are rare CDKN2A accounts for up to 25% of melanoma families CDKN2A accounts for up to 25% of melanoma families p16 involved in cell cycle and senescence p16 involved in cell cycle and senescence

30. Genes et Naevus 60% of the variation in naevus number is determined by genetic factors 60% of the variation in naevus number is determined by genetic factors Twin studies. St Thomas. More than 2000 twins Twin studies. St Thomas. More than 2000 twins Why is there such a great variation in naevi number in Caucasian populations? Why is there such a great variation in naevi number in Caucasian populations? Why do genes disappear with age? Why do genes disappear with age?

31. 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 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 Less wrinkles, less solar lentigines and fewer solar keratoses What is the significance of this? What is the significance of this?

32. Telomeres Telomeres-DNA sequence at the end of telomeres Telomeres-DNA sequence at the end of telomeres Non coding DNA Non coding DNA Biological clock which shortens with age Biological clock which shortens with age The speed of telomere shortening with age varies between individuals which is in part genetically determined 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 Smoking, obesity and chronic diseases can shorten telomere further

33. Telomere length in relation to naevus counts

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

35. Naevus marker of reduced senescence Naevus may therefore be a good marker of reduced ageing 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 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 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 May provide a survival advantage in the selective gene pool

36. Vit D and sun exposure Is Vitamin D deficiency relevant? Is Vitamin D deficiency relevant? Vitamin D protects against osteoporosis, cancer, inflammatory and autoimmune disorders Vitamin D protects against osteoporosis, cancer, inflammatory and autoimmune disorders 1400 Caucasian females: 10% had Vit D serum levels below 30 nmol/L 1400 Caucasian females: 10% had Vit D serum levels below 30 nmol/L Skin type 1 and 2 more prone to Vit D deficiency Skin type 1 and 2 more prone to Vit D deficiency Vitamin D may also increase melanoma survival Vitamin D may also increase melanoma survival Need to be more cautious when recommending sun avoidance Need to be more cautious when recommending sun avoidance