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Updated: May 3 2022


Images 2.jpg melanoma.jpg
  • Snapshot
    • A 46-year old woman presents to her primary care physician for a dark spot on the back of her right hand. She states that the spot first appeared about 2 years ago and has slowly been growing. It does not burn, itch, or sting. She has a history of regular suntanning and minimal sunscreen use. On exam, there is a 2-cm, asymmetric, thin, brownish-blue plaque with somewhat ill-defined borders and an irregular pattern of coloration.
  • Introduction
    • Overview
      • malignant tumor of melanocytes
        • most commonly affects the skin
          • other sites of involvement
            • brain
            • uvea
            • intestines
            • mucosa
        • melanocytes are of neural crest cell origin
        • 4 types of cutaneous invasive melanoma
          • superficial spreading (most common)
            • usually seen in sunexposed areas
          • nodular (second most common)
            • usually seen in men and often associated with ulceration
          • acral
            • most commonly seen in Asians, Hispanics, and patients from African descent
          • lentigo maligna (invasive melanoma)
            • typically seen in elderly patients
    • Epidemiology
      • incidence
        • most commonly seen between the ages of 40-60
      • risk factors
        • dysplastic nevi
        • multiple nevi
        • ultraviolet radiation exposure
        • fair-skin color
        • immunsuppresion
    • Pathophysiology
      • Clark model of pathogenesis
        • melanocytes proliferate to form a benign nevus
        • genetic mutations (e.g., BRAF) lead to the nevus to become dysplastic (pre-malignant)
          • radial growth → vertical growth
            • can eventually metastasize
          • BRAF mutation
            • seen in ~50% of patients with metastatic cutaneous melanoma
            • secondary to a valine-to-glutamic acid substitution at codone 600 (V600E)
    • Prognosis
      • prognostic favorable
        • favorable
          • localized disease with the tumor being ≤ 1 mm deep
        • negative
          • metastatic disease
  • Presentation
    • Physical exam
      • pigmented skin lesion
        • ABCDEs
          • Asymmetric
          • Border irregularity
          • Color variation
          • Diameter ≥ 6 mm
          • Evolution over time
  • Studies
    • Serum labs
      • S-100 tumor marker
    • Invasive studies
      • excisional biopsy
        • indication
          • preferred biopsy method to confirm the diagnosis
        • findings
          • atypical melanocytes and architectural disorder
            • atypical
              • larger than normal melanocytes
              • large hyperchromatic nuclei
              • irregular nuclear shape
              • abnormal chromatin pattern
            • architectural disorder
              • asymmetry
              • nests of melanocytes of varying sizes and shapes
  • Differential
    • Actinic keratosis
      • differentiating factors
        • secondary to proliferation of atypical epiderminal keratinocytes
        • lesions are small, rough papules that are erythematous or brownish
    • Basal cell carcinoma
      • differentiating factors
        • lesions are waxy, pink, and pearly
          • can have central crusting or ulceration
        • histology demonstrates palisading nuclei
  • Treatment
    • Medical
      • vemurafenib
        • indication
          • BRAF kinase inhibitor that can be considered in patients with metastatic or unresectable melanoma with BRAF V600E mutations
            • typically given with cobimetinib
        • can lead to T cell mediated destruction of malignant melanocyte
    • Surgical
      • wide local excision
        • indication
          • mainstay of treatment for primary cutaneous melanoma
  • Complications
    • Metastatic melanoma
      • lung
      • brain
      • liver
      • bone
      • intestines
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