Learning Objectives

  • Review basic epidemiology of melanoma
  • Review molecular mechanisms of melanoma
  • Discuss risk factors for melanoma
  • Review how to evaluate and stage patients
  • Overview of management of melanoma


  • 1:25 Americans will get some kind of melanoma in their lifetime
  • 1:52 Americans will get an invasive melanoma in their lifetime
  • Estimated to be 96,480 newly diagnosed cases of invasive melanoma in the U.S. in 2019
    • 95,830 cases of melanoma in situ
  • Between 9,000-10,000 deaths annually

Hallmarks of Cancer

  • Self-sufficiency of growth signals
  • Insensitivity to anti-growth signals
  • Evading apoptosis
  • Limitless replicative potential
  • Sustained angiogenesis
  • Tissue invasion and metastasis

Ref: Hanahan and Weinberg. Cell 2000. Vol 100

Hallmarks of Cancer - Updated

  • Deregulating Cellular Energetics
  • Genome Instability and Mutation
  • Avoiding Immune Destruction
  • Tumor-promoting Inflammation

Ref: Hanahan and Weinberg. Cell 2011.

Melanoma Pathogenesis

Oncogenes and Tumor Suppressors

Oncogenes in Melanoma

Oncogene-Induced Senescence

Why don’t all melanocytes undergo oncogene-induced senescence?

Risk Factors for Melanoma - Genetics

Susceptibility to Cutaneous Malignant Melanoma (CMM)

  • There are numerous loci that have been identified that predispose patients to melanoma Several familial syndromes have been described
    • E.g. in 1978, Clark et al pointed out distinctive clinical and histologic features of the moles that are precursors of familial malignant melanomas

CMM - BK Mole Syndrome

  • B-K Mole Syndrome (named after family names of 2 of the patients)
    • Aka FAMMM (Familial Atypical Mole-malignant Melanoma)
  • Penetrance
    • 58% to 92% by 80 years of age and varies with geography

CMM Genetics

  • CMM1 has been mapped to chromosome 1p36.
  • CMM2 – CDKN2A (9p21)
  • CMM3 – CDK4 (12q14)
  • CMM4 – mapped to chromosome 1p22
  • CMM5 – MC1R (16q24)
  • CMM6 – XRCC3 (14q32)
  • CMM7 – mapped to chromosome 20q11
  • CMM8 – MITF (3p13)
  • CMM9 – TERT (5p15)
  • CMM10 – POT1 (7q31)

Predominantly Somatic Mutations in Purple

CMM Mutations in Yellow

Diagnosis and Work Up


  • Ideally, a patient with a lesion suspicious for melanoma should have a narrow excisional biopsy
  • This biopsy can be performed with a variety of techniques
    • Elliptical excision
    • Punch biopsy
    • Saucerization