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