Melanoma

• 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
    • Non-pigmented nodule
• 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