Diagnosis

Ask about risk factors evolution, systemic symptoms

TBSE, lymph node exam to look for:

  • ABCDE: Asymmetry, Borders irregularity, Colour variation, Diameter >5mm, Evolution (EFG rule: Elevated, Firm, Growing; helpful in amelanotic or nodular types)
  • Ugly duckling sign
  • Little red riding hood sign
  • Garbe’s rule: If a patient is concerned about an individual cutaneous lesion, do not ignore and biopsy

Dermoscopy:
  • Many algorithms, simplest is 2-step:
    • Melanocytic or not (pigment network)
    • Suspicious or not
  • 7-point checklist (≥3 = melanoma): (*=points)
    • Atypical network**
    • Atypical vascular pattern**
    • Blue-white veil**
    • Atypical dots and / or globules*
    • Atypical streaks*
    • Atypical / Off-centered blotch*
    • Regression pattern*: scar-like area, peppering
    • Other: negative pigment network, shiny white lines (chrysalis / crystalline), structureless area
  • Lentigo maligna melanoma dermoscopy: Annular granular, circle in circle, rhomboidal structures

Excisional biopsy with narrow marings, if not possible, incisional/punch(es) or saucerization

  • Atypical melanocyte (pleomorphic / large nuclei, mitosis, necrosis) with abnormal overall architecture (asymmetric, abnormal nest, no maturation and dispersion), pagetoid spread
  • Lentigo malignant melanoma: Lentiginous proliferation, involvement of adnexa, pagetoid spread ++ solar elastosis

Must report: diagnosis of melanoma + Breslow depth + ulceration + margins. Others extra: Regression, dermal fibrosis, inflammation, melanophages, neovascularization, effacement

Microstaging:
  • Depth (Breslow): from top of granular layer to deepest tumor point. Strongest predictor of survival
  • Depth (Clark)
    • I: Epidermis
    • II: Invasion of papillary dermis
    • III: Fills papillary dermis
    • IV: Invasion of reticular dermis
    • V: Invasion of subcutaneous tissue
  • Mitosis = more aggressive
  • Ulceration
  • Microsatellite: Nests ≥ 0.05mm, ≥ 0.3mm away from tumour with normal dermis between
  • Lymphovascular invasion
  • Perineural invasion
Immunostaining
  • Melanin stain: Fontana masson
  • Immunohistochemical stain: most sensitive stain is S100, most specific is HMB45
  • Nuclear immunohistochemical stain: MITF, SOX-10
  • Desmoplastic melanoma: SOX-10
  • Spindle cell melanoma: S100
  • Melanocyte differentiation antigen: Tyrosinase, HMB45, Melan-A / MART-1
Molecular analysis
  • Comparative genomic hybridization (CGH): useful to differentiate spitz from Spitzoid melanoma (~20% of Spitz nevi have 11p gain)
  • Fluorescent in situ hybridization (FISH): specific chromosomal loci
  • Gene expression profiling (GEP): Prognosticate risk

TNM

T → all T have A and B, based on Breslow

  • Tis → Epidermis only
  • T1 → ≤1.0 mm → a. no ulceration, <0.8mm, b. with ulceration OR ≥ 0.8mm
  • T2 → 1.01–2.0 mm, b. with ulceration
  • T3 → 2.01–4.0 mm, , b. with ulceration
  • T4 → >4.0 mm, , b. with ulceration
  • T2, T3, T4: a. no ulceration, b. with ulceration

N →all N have A, B, C

  • N0 → 0 node
  • N1 → 1 node (A. clinically occult, B. clinically detected) OR C. in-transit, satellite, microsatellite without nodes
  • N2 → 2-3 node → (A. clinically occult, B. clinically detected) OR C. in-transit, satellite, microsatellite with 1 node
  • N3 → ≥ 4 nodes (A. clinically occult, B. clinically detected) OR C. in-transit, satellite, microsatellite with 2 nodes OR any matted nodes
Metastases
  • M0 → No distant metastasis
  • M1 → Any distant metastasis (M1A:skin, soft tissue; M1B: lung; M1C: visceral sites; M1D: CNS) → normal/ elevated serum lactase dehydrogenase
Staging (AJCC) 8th version
  • Stage 0 (Tis): in situ
  • Stage IA-B (T1a → T2a, N0): localized
    • 5-year survival > 90%
  • Stage IIA-C (T2b → T4b, N0): localized
    • 5-year survival 50-80%
  • Stage IIIA-D (Any T, N≥1): regional nodal or intralymphatic metastases
    • 5-year survival 40-75%
  • Stage IV (M1): distant metastases
    • 5-year survival 10-25%