Melanoma

Melanoma 

Updated: 03/10/2023

© Jun Wang, MD, PhD

General features
  • Malignancy of melanocytes, predominantly in skin
  • May involve eyes, ears, GI tract, leptomeninges, mucous membranes
  • Majority of skin cancer deaths
  • More common in older population
  • Strong association with UV light (sun or artificial) exposure
  • Melanoma in situ: Atypical melanocytes limited in epidermis
  • Invasive melanoma: Atypical melanocytes invade into dermis and beyond
  • Prognostic factors: depth of invasion (Clark’s levels or Breslow thickness), nodal status, etc
    • Thin: < 1 mm
    • Moderate: 1-4 mm
    • Thick: > 4 mm
Risk factors
  • Excessive UV light exposure, including indoor tanning
  • Living closer to the equator or at a higher elevation
  • History of sunburn
  • Fair skin
  • Multiple nevi or dysplastic nevi
  • Family history of melanoma
  • Weakened immune system
Pathogenesis
  • Complex
Pro-growth signaling pathway: RAS/BRAF, PI3K-ATK/PTEN, Gain of function
Cell cycle control: CDKN2A (p14, p16) Loss of function, cKIT (over-expression)
Telomerase activity: TERT promoters, Gain of function
Clinical features
Periungual extension of brown-black pigmentation onto the proximal and lateral nail folds
May be seen associated with benign melanocytic nevi, subungual hematomas, Bowen’s disease
Pathological features
Epithelioid: polygonal cells
Spindled: elongated nuclei
  • Two phases of growth
Radial phase: horizontal spread of tumor cells
Vertical phase: downward invasion
  • Four major subtypes of melanoma
Superficial spread: Slight elevated, or flat growth
Lentigo maligna: Usually flat growth
Acral lentiginous: Acral skin, more common in people with darker skin
Nodular: Rapid growth, aggressive clinical course, smooth nodules covered by normal epidermis, well demarcated nodules of malignant melanocytes,

Marker
  • Positive: S100, HMB45, melan A, tyrosinase
  • Negative: cytokeratin
Differential diagnosis
  • Non melanocytic: Morphology and negative reactivity to HMB45, MelanA and S100
  • Granular cell tumor: Negative for HMB45 and MelanA
  • Amelanotic melanoma: resemble pyogenic granuloma, positive for S100, HMB45
  • Nevi: normal maturation, symmetry, no atypia, no Pagetoid spread, no necrosis
  • Paget’s disease: Positive for CK7 and CAM5.2, Negative for HMB45, MelanA and S100
Management
  • Surgery
  • Immune therapy: Antibodies against CTLA4 and PD1
  • Targeted therapy: BRAF w/ or w/o MEK inhibitor; KIT inhibitor
  • Chemotherapy
  • Interferon alpha



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