Melanoma

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