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10. Pigmented Skin Lesions MELANOMA

11. Malignant melanoma is a skin cancer due to uncontrolled growth of pigment cells - melanocytes.

12. Melanocytes Normal melanocytes occur in the basal layer of the epidermis They produce melanin Melanin (a protein) protects the skin by absorbing ultraviolet (UV) radiation Melanocytes are found in equal numbers in black and in white skin Melanocytes in black skin produce much more melanin Non-cancerous growth of melanocytes results in moles (benign melanocytic naevi) and freckles Cancerous growth of melanocytes results in melanoma

13. Risk Factors for Melanoma Sun exposure, particularly during childhood Fair skin that burns easily Blistering sunburn, especially when young Previous melanoma Previous non-melanoma skin cancer (BCC, SCC) Family history of melanoma Large numbers of moles (esp if > 100) Abnormal moles (atypical or dysplastic naevi)

14. Epidemiology of Melanoma 3% of all cancers and 10% of skin cancers. Incidence 1:10,000 per annum Incidence is increasing in developed countries Incidence rises with age, rare in children, commonest in over 75s 3rd commonest cancer in young people. In UK 2002 - 1,640 deaths from malignant melanoma Over 65% of deaths from malignant melanoma were in the over 65s. It is commoner in women than in men but men have a worse prognosis.

15. Melanoma in situ Superficial forms of melanoma spread out within the epidermis (horizontal growth). If all the melanoma cells are confined to the epidermis, it is melanoma in situ. Lentigo maligna is a special case of melanoma in situ that occurs around hair follicles on the sun damaged skin of the face or neck. Melanoma in situ is cured by excision

16. Invasive Melanoma When the cancerous cells have grown through the basement membrane into the deeper layer of the skin (the dermis), it is known as invasive melanoma (vertical growth) Nodular melanoma appears to be invasive from the beginning, and has little or no relationship to sun exposure. Metastatic disease increases in likelihood with increasing depth of the melanoma. 15% of people with invasive melanoma will die from it.

17. Where do melanomas occur? Melanoma can arise from otherwise normal appearing skin (50%) Or from within a mole or freckle, which starts to grow larger and change in appearance. Precursor lesions include: –Congenital melanocytic naevus (brown birthmark) –Atypical or dysplastic naevus (funny-looking mole) –Benign melanocytic naevus (normal mole) Melanomas occur anywhere on the skin, not only in sun-exposed areas. Commonest sites: men - back (40%), women - leg (40%). Melanomas can also occur on mucous membranes (lips, genitals). May also occurs in other parts of the body such as the eye, brain, mouth or vagina.

18. Moles (Melanocytic Naevi) Very common May be flat or protruding Vary in colour from pink to black Brown or black coloured moles are also called ‘pigmented naevi’. Mostly round or oval in shape Range in size from 2mm to several cm

19. Moles Most frequently moles arise during childhood or early adult life (acquired melanocytic naevi). Exposure to sunlight increases the number of moles. Teenagers and young adults tend to have the greatest number of moles.

20. Classification Junctional naevi Groups or nests of naevus cells at the junction of the epidermis and dermis. Tend to be flat colourful moles. Dermal/Intradermal naevi Nests of naevus cells in the dermis. These moles are thickened and often protrude from the skin surface (papillomatous naevi). Compound naevi Nests of naevus cells at the epidermal-dermal junction as well as within the dermis. These moles have a central raised area surrounded by flat pigmentation.

21. Junctional Naevus

22. Congenital Melanocytic Naevus Brown or black naevi Present at birth or develop in the first year or so of life Moles that look like birthmarks but were not present at birth may be called ‘congenital naevus-like’ naevi or ‘congenital-type’ naevi. About one baby in 100 has a small or medium sized congenital naevus, so they are quite common. Very large, giant or bathing trunk naevi are very rare.

23. Types of congenital melanocytic naevus Typically multi-shaded, oval, fairly uniform pigmented patches Most grow with the child but become proportionally smaller and less obvious with time. May darken, become bumpy or hairy especially at puberty. Rarely fade away or disappear. Congenital melanocytic naevi in adults are classed as ‘small’ ( 1.5 10cm) ‘Giant’ congenital naevi are greater than 20cm in diameter. Often found on the buttocks (‘bathing trunk’ naevi) Café-au-lait macule - a flat tan mark, usually oval (inherited). Multiple café-au-lait macules may be a sign of neurofibromatosis. Speckled lentiginous naevus (naevus spilus) has dark spots scattered on a flat tan background.

24. Risk of Melanoma The risk of melanoma in a small or medium-sized congenital melanocytic naevus is very small (< 1%) Melanoma never arises from café-au-lait macules Melanoma is more likely in the giant naevi (~ 5% over a lifetime) especially in those that lie across the spine

25. Congenital Melanocytic Naevus

26. Café au lait Macule

27. Giant Melanocytic Naevus

28. Speckled Melanocytic Naevus

29. Atypical Naevi Melanocytic naevi with unusual features eg indistinct edge, larger size. May resemble Malignant Melanomoa but are benign Sometimes called dysplastic naevi, active junctional naevi, B-K moles and Clark's naevi. May be familial or sporadic. The inherited form is usually part of a syndrome - Familial Atypical Mole and Melanoma (FAMM) syndrome (formerly dysplastic naevus syndrome). –One or more first-degree or second-degree relative with malignant melanoma –A large number of naevi (often more than 50) some of which are atypical naevi –Naevi that show certain histological features.

30. Atypical Naevi Fair-skinned individuals with light coloured hair and freckles are most at risk of getting atypical naevi, especially if they have been frequently exposed to the sun or have a family history of atypical naevi. Atypical naevi may develop at any time but most develop during the first 15 years of life.

31. Atypical Naevi People with one to four atypical naevi have a slightly higher risk than the general population of developing malignant melanoma People with FAMM syndrome are significantly more at risk of developing melanoma. Atypical naevi are harmless (benign) and do not need to be removed. However, it is not always easy to tell whether a lesion is an atypical naevus or a melanoma, so if in doubt, it should be removed by excision biopsy.

32. Atypical Naevus

34. Glasgow 7-point Checklist Major features –Change in size –Irregular shape –Irregular colour Minor features –Diameter >7mm –Inflammation –Oozing –Change in sensation

35. ABCDE of Melanoma A.Asymmetry B.Border - irregularity C.Colour - variation D.Diameter - over 6 mm E.Evolving - (enlarging, changing)

36. Types of Melanoma Flat patches (horizontal slow growth) –Superficial spreading melanoma (SSM) –Lentigo maligna melanoma (sun damaged skin of face, scalp and neck) –Acral lentiginous melanoma (on soles of feet, palms of hands or under the nails – the subungual melanoma) Nodules (vertical rapid growth) –Nodular melanoma –Mucosal melanoma (arising on lips, eyelids, vulva, penis, anus) –Desmoplastic melanoma (fibrous tumour with a tendency to grow down nerves) Combinations occur e.g. nodular melanoma arising within a superficial spreading melanoma.

37. Typical Superficial Spreading Melanoma

38. Superficial Spreading Melanoma with regression

39. Amelanotic Melanoma

40. Lentigo Maligna

41. Lentigo Maligna Melanoma

42. Lentigo Maligna Sun-exposed areas of the face and neck Elderly Slow growing Often quite large (>20mm). Pre-cancerous Conversion to a lentigo maligna melanoma occurs in ~ 5% of patients Identifying lesions that require referral is not easy – but see ABCDE

43. Nodular Melanoma in Lentigo Maligna

44. Acral Lentiginous Melanoma

45. Subungual Melanoma

46. Amelanotic Subungual Melanoma

47. Nodular Melanoma

50. Diagnosis Excision biopsy with a 2 to 3-mm margin Breslow depth - thickness of the melanoma in mm Clark's level - describe which layer of the skin has been breached. Clark’s level 1 refers to melanoma in situ. Invasive melanoma may reach Clark's level 2 (thin) to 5 (reaching the subcutaneous fat layer). Systematic search for metastasis

51. Prognosis Death is unlikely if a melanoma has a Breslow thickness of less than 1mm 50% dead within 5 years if >4mm