Skin & Soft Tissue: Melanoma

Melanoma

Basics

  • Tumor from Basal Melanocytes
  • Highest Skin Cancer Mortality

Risk Factors

  • Sun Exposure
  • History of Melanoma
  • Multiple Atypical Moles or Dysplastic Nevi
  • Genetic Mutations

Presentation

  • Classic “ABCDE” Appearance:
    • Asymmetric
    • Borders Irregular
    • Color Variegation
      • Most Ominous Color: Blue
    • Diameter > 6 mm
    • Evolution Over Time
  • Pigmented Lesion Out of Character with the Patient’s Mole Pattern
  • New Pigmented Lesion After Age 40

Melanoma 1

Location

  • Most Common Site:
    • Men: Back
    • Women: Legs
  • Mets:
    • Most Common Mets: Lung
    • Melanoma is the Most Common Met to the Small Bowel
  • Associated with S-100 Protein (Also Seen in Neurofibroma & Schwannoma)

Types

  • In Situ (Hutchinson’s Freckle)
    • Epidermis Only
  • Lentigo Maligna
    • Least Aggressive Subtype
  • Superficial Spreading
    • Most Common Type
    • Radial Growth Initially, But Can Grow Vertically if Untreated
  • Acral Lentiginous
    • Palms/Soles of Blacks
    • Very Aggressive
    • Subungual: Below Fingernail
  • Nodular
    • Vertical Growth First
    • Most Aggressive

Lentigo Maligna 2

Superficial Spreading 1

Acral Lentiginous 3

Subungual 4

Nodular 5

Prognosis

  • Poor Prognosis:
    • Depth (Not Level of Invasion)
    • Stage
    • LDH
    • Ulceration
    • Mitotic Rate
    • Node Status – Most Important
  • Breslow Thickness
    • Based on Total Depth
  • Clark Level (Not Used Anymore)
    • Based on Level of Invasion
    • I: Epidermis (In Situ)
    • II: Papillary Dermis
    • III: Junction of Papillary/Reticular Dermis
    • IV: Reticular Dermis
    • V: Subcutaneous

Melanoma Clark Level 6

Melanoma – TNM Staging (AJCC 8)

TNM

  T N M
1 ≤ 1.0 mm
1a: < 0.8 mm without Ulceration
1b: ≥ 0.8 mm without Ulceration or ≤ 1.0 mm With Ulceration		 1+ LN 1a: Distant Skin, Soft Tissue or LN
1b: Lung
1c: Visceral Sites
1d: CNS
2 > 1.0 mm 2-3+ LN
3 > 2.0 mm ≥ 4+ LN
4 > 4.0 mm
    • T Stage Sub-Staging:
      • TXa: Without Ulceration
      • TXb: With Ulceration
    • N Stage Sub-Staging:
      • NXa: Clinically Occult
      • NXb: Clinically Detected
      • NXc: Presence of In-Transit, Satellite and/or Microsatellite Metastases
        • N1c: No LN+
        • N2c: 1 LN+
        • N3c: ≥ 2 LN+
    • M Stage Sub-Staging:
      • M1x(0): LDH Not Elevated
      • M1x(1): LDH Elevated

Stage

Stage T N M
I A T1a-b N0 M0
B T2a N0 M0
II A T2b-3a N0 M0
B T3b-4a N0 M0
C T4b N0 M0
III A T1a/b-T2a N1a or N2a M0
B T0 N1b/c M0
T1a/b-T2a N1b/c or N2b M0
T2b-T3a N1a-N2b M0
C T0 N2b-N2c or N3b-N3c M0
T1a-T3a N2c-N3c M0
T3b-T4a N1a-N3c M0
T4b N1a-N2c M0
D T4b N3a-N3c M0
IV   Any T Any N M1

Melanoma – Treatment

Management of Primary Lesion

  • If Previously Diagnosed by Shave-Biopsy with Positive Deep Margin: Need Full Thickness Biopsy to Determine Depth
  • Primary Treatment: Wide Local Excision
  • Margins: Mn
    • In Situ: 0.5-1.0 cm
    • ≤ 1.0 mm Depth: 1.0 cm
    • > 1.0 mm Depth: 1.0-2.0 cm
    • > 2.0 mm Depth: 2.0 cm
  • In General Length to Width Ratio of 3:1 Required to Allow Primary Closure
  • Subungual Melanomas: Amputation of Distal Digit (1 cm Margin)

Management of Lymph Nodes

  • Consider Systemic Immunotherapy for any Stage III Disease
  • Clinically Palpable Lymph Nodes: FNA (Fine Needle Aspiration)
    • Resect if Positive (Goal is to Clear, Not to Stage)
  • Sentinel Lymph Node Biopsy (SLNB)
    • Indications: ≥ T1b (≥ 0.8 mm or Ulcerating)
    • Indications for Node Retrieval:
      • Dye: All Nodes That Have Taken Up Dye
      • Radiotracer: All Nodes with > 10% Highest Ex-Vivo Count
      • Any Firm Node, Regardless of Dye/Radiotracer
    • Most Commonly Sent for Permanent Pathology – Frozen Section Generally Abandoned Due to Low Sensitivity
  • Completion Lymphadenectomy:
    • Axillary Lymph Node Dissection (ALND)
      • Indications: Positive SLNB or Axillary Nodes with No Primary
      • Include Level III Nodes for Melanoma
    • Groin Dissection
      • Superficial Groin (Inguinofemoral) Dissection
        • Indications: SLNB Positive
        • Femoral Triangle Borders:
          • Lateral: Sartorius
          • Medial: Adductor Longus
          • Superior: Inguinal Ligament
      • Deep Inguinal (Iliac-Obturator) Dissection
        • Indications:
          • Positive Cloquet’s Lymph Node – Within Femoral Canal (Bridge Between Superficial & Deep Nodal Basins)
          • > 4 Positive Lymph Nodes on Superficial Dissection
          • Enlarged Ileo-Obturator Lymph Nodes on Preoperative Imaging
          • Clinically Palpable or Extracapsular Invasion of Femoral Lymph Nodes
        • Procedure:
          • Divide Inguinal Ligament Medially (Avoid Femoral Vessels)
          • Start at Common Iliac Vessels and Extend Caudally
          • Suture Inguinal Ligament to Lacunar Ligament to Close Femoral Canal
          • Close Residual Defects with Mesh or Sartorius Flap
  • If Sentinel LN+ May Consider US Observation:
    • Observation with US & Completion LN Dissection Have Similar Melanoma-Specific Survival
    • US Schedule:
      • Every 4 Months for 2 Years
      • Then Every 6 Months for 3 Years
      • Then Annually

Management of Metastases

  • Limited (Resectable): Systemic Therapy & Resect
  • Disseminated (Unresectable): Systemic Therapy

Systemic Therapies

  • Immunotherapy:
    • Nivolumab: Monoclonal Antibody (mAb) Against PD-1
    • Pembrolizumab: Monoclonal Antibody (mAb) Against PD-1
    • Ipilimumab: Monoclonal Antibody (mAb) Against CTLA-4
  • Molecular Targeted Therapy for BRAF V600-Activating Mutations:
    • Dabrafenib (BRAF Inhibitor) & Trametinib (MEK Inhibitor)
    • Vemurafenib (BRAF Inhibitor) & Cobimetinib (MEK Inhibitor)
    • Encorafenib (BRAF Inhibitor) & Binimetinib (MEK Inhibitor)

Axillary Lymph Node Levels 7

Superficial Groin Dissection 8

Mnemonics

Melanoma Margins

  • ≤ 1 mm: 1 cm
  • 1-2 mm: 1-2 cm
  • > 2 mm: 2 cm

References

  1. National Cancer Institute. Wikimedia Commons. (License: Public Domain)
  2. Bari O, Cohen P R (February 13, 2017) Tumoral Melanosis Associated with Pembrolizumab-Treated Metastatic Melanoma. Cureus 9(2): e1026. (License: CC BY-3.0)
  3. Xavier-Júnior, J.C.C., Munhoz, T., Souza, V. et al.Focal invasiveness in complete histological analyses of a large acral lentiginous melanoma. Diagn Pathol 10, 73 (2015). (License: CC BY-4.0)
  4. Wawjak. Wikimedia Commons. (License: CC BY-4.0)
  5. Ox6adb015. Wikimedia Commons. (License: CC BY-SA-3.0)
  6. Leilabadi SN, Chen A, Tsai S, Soundararajan V, Silberman H, Wong AK. Update and Review on the Surgical Management of Primary Cutaneous Melanoma. Healthcare (Basel). 2014 Jun 10;2(2):234-49. (License: CC BY-3.0)
  7. Lu Q, Hua J, Kassir MM, Delproposto Z, Dai Y, Sun J, Haacke M, Hu J. Imaging lymphatic system in breast cancer patients with magnetic resonance lymphangiography. PLoS One. 2013 Jul 5;8(7):e69701. (License: CC BY-4.0)
  8. Sotelo R, Cabrera M, Carmona O, de Andrade R, Martin O, Fernandez G. Robotic bilateral inguinal lymphadenectomy in penile cancer, development of a technique without robot repositioning: a case report. Ecancermedicalscience. 2013 Sep 26;7:356.(License: CC BY-3.0)