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- Epidemiology
- Only 2% of skin cancer
- Responsible for most skin cancer-related deaths
- Higher incidence in sun-rich countries like Australia compared to Europe
- Paradoxically common in Northern Europe
- Average age at onset ~50
- Risk factors
- Excessive UV exposure
- Especially high doses over short period, in contrast to non-melanoma skin cancer
- Fitzpatrick skin type I and II
- Easily burns
- Almost never suntans
- Often have freckles
- Precancerous lesions
- Dysplastic nevi
- Dysplastic nevus syndrome – 100% risk of developing melanoma
- Lentigo maligna
- Congenital nevi
- Indoor tanning
- Sunburns in childhood (> 3)
- Positive family history
- Immunosuppression
- Familial genetic mutations
- BRAF (most common)
- NRAS
- p16 family
- Pathology
- BRAF mutation is found in 50%
- Breslow depth, mitotic rate and presence of ulceration on histology are important prognostic factors
- 2 growth phases:
- Radial/horizontal growth phase
- Tumor grows horizontally along epidermis
- No capacity to metastasize
- Vertical growth phase
- Tumor grows vertically into the dermis
- Can metastasize
- Subtypes
- Superficial spreading melanoma
- 60% of all cases
- Slow radial growth phase, mostly superficial spreading
- Nodular melanoma
- 20% of all cases
- Reddish-brownish-blackish nodule
- Can be ulcerated
- Has no radial growth phase, only vertical
- Poorer prognosis
- Lentigo maligna melanoma
- 10% of cases
- Originates from lentigo maligna in elderly
- Slow radial growth phase
- Lesion is often a large and irregularly shaped patch
- Acral lentiginous melanoma
- 5% of cases
- Slow radial growth phase
- Occurs on nailbeds, palms and soles of dark-skinned and Asian persons
- Unrelated to UV exposure
- Amelanotic melanoma
- Clinical features
- Pruritic, bleeding skin lesion
- On the back or chest in men
- On extremities in women
- Diagnosis
- Presumptive clinical diagnoses made with ABCDE criteria – these help distinguish between naevi and melanoma
- Asymmetry
- Border irregular
- Colour irregular
- Diameter enlarged (> 5 mm)
- Evolution (changes over time)
- Ugly duckling sign
- The lesion looks different from other nevi on the same patient
- Dermoscope
- Histopathological
- Gives definitive diagnosis
- Full-thickness biopsy with 1 – 2 mm safety margin
- Shows atypical melanocytes and atypical architecture
- Important to look for BRAF mutation in the biopsy
- Prognosis
- Breslow depth – from the top of the stratum granulosum to the deepest invasive cell
- Presence of ulceration
- Number of mitoses
- Clark level
- The subtype
- Presence of metastasis
- Usually metastasizes to liver, lung, brain, bone
- Can metastasize into unusual locations like the heart and gallbladder
- Metastases are black
- Localized disease – cancer confined to primary site
- 84% of cases
- 98% 5-year survival
- Regional disease – cancer spread to regional lymph nodes
- 9% of cases
- 63% 5-year survival
- Metastatic disease – cancer has metastasized
- 4% of cases
- 22% 5-year survival
- Staging
- TNM
- T = Based on Breslow depth
- “a” – if there is no ulceration
- “b” – if there is ulceration
- N – lymph node
- Any melanoma with lymph node involvement is stage III
- M – metastasis
- Any melanoma with metastasis is stage IV
- Treatment
- Immediate complete excision upon clinical suspicion is the gold standard
- A sufficiently large safety margin (1 – 2 cm, depending on Breslow stage) must be used
- Non-surgical treatment
- For stage III and stage IV melanoma
- Immune checkpoint inhibitors
- Commonly used for advanced disease
- Anti-CTLA-4 antibodies (Ipilimumab)
- Anti-PD-1 antibodies (Nivolumab, Pembrolizumab)
- Inhibitors of mutated proteins
- BRAF inhibitor – dabrafenib, trametinib
- MEK inhibitor – trametinib
- Chemotherapy is not used