Updated: 12/12/2020

Melanoma

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Questions
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Key Images
https://upload.medbullets.com/topic/114065/images/melanoma 2.jpg
https://upload.medbullets.com/topic/114065/images/acral_lentiginous_melanoma.jpg
https://upload.medbullets.com/topic/114065/images/nodularmelanoma.jpg
https://upload.medbullets.com/topic/114065/images/lentigomaligna 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
  • Surgical
    • wide local excision
      • indication
        • mainstay of treatment for primary cutaneous melanoma
Complications
  • Metastatic melanoma
    • lung
    • brain
    • liver
    • bone
    • intestines
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(M1.ON.14.19) A 63-year-old male has been referred to the dermatologist for evaluation of a concerning skin lesion (pictured in Figure A). The man first noticed the lesion years ago, but believes it has changed in the last 2 months. He notes it is changing color and has become itchy. He is very concerned because his mother was diagnosed with basal cell carcinoma in her 60s. As the dermatologist, which of the following factors is most important for prognosis of this lesion? Tested Concept

QID: 103812
FIGURES:
1

Depth of invasion of the lesion

84%

(147/174)

2

Number of dysplastic cells within the lesion

7%

(13/174)

3

Patient's age

1%

(1/174)

4

Pruritic lesion

0%

(0/174)

5

Patient's family history

6%

(10/174)

M 4 D

Select Answer to see Preferred Response

(M1.ON.13.1) A 52-year-old Caucasian male presents to your office with an 8 mm dark lesion on his back. The lesion, as seen below, has irregular borders and marked internal color variation. Upon excisional biopsy, the presence of which of the following would best estimate the risk of metastasis in this patient’s lesion: Tested Concept

QID: 101307
FIGURES:
1

Palisading nuclei

9%

(2/23)

2

Keratin pearls

0%

(0/23)

3

Vertical tumor growth

70%

(16/23)

4

Cellular atypia

13%

(3/23)

5

Increased production of melanosomes

9%

(2/23)

M 4 E

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(M1.ON.13.1) A 61-year-old Caucasian male presents to your office complaining of morning headaches of 6 weeks duration. A head MRI reveals a likely metastasis of unknown origin in the supratentorial region of the brain. On biopsy, the neoplastic mass is shown to have a mutation in BRAF, a protein kinase, in which a glutamic acid is substituted for valine at position 600 of the protein. Where did this metastasis most likely originate? Tested Concept

QID: 101301
1

Stomach

7%

(11/156)

2

Breast

12%

(18/156)

3

Bone

19%

(29/156)

4

Skin

60%

(93/156)

5

Brain

2%

(3/156)

M 1 D

Select Answer to see Preferred Response

Evidence (5)
Topic COMMENTS (11)
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