Updated: 8/17/2019

Melanoma

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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
      • 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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Questions (5)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.ON.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? Review Topic

QID: 103812
FIGURES:
1

Depth of invasion of the lesion

84%

(139/166)

2

Number of dysplastic cells within the lesion

8%

(13/166)

3

Patient's age

1%

(1/166)

4

Pruritic lesion

0%

(0/166)

5

Patient's family history

6%

(10/166)

M1

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SUBMIT RESPONSE 1

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(M1.ON.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: Review Topic

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)

M1

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SUBMIT RESPONSE 3

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(M1.ON.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? Review Topic

QID: 101301
1

Stomach

6%

(9/145)

2

Breast

12%

(17/145)

3

Bone

18%

(26/145)

4

Skin

61%

(89/145)

5

Brain

1%

(2/145)

M1

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SUBMIT RESPONSE 4
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