Key Facts

Melanoma is the 5th most common cancer in the UK. Early detection and excision are curative. Advanced melanoma treatment has been revolutionised by immunotherapy and targeted therapy.

Epidemiology

• UK: ~16,000 new cases/year; ~2,300 deaths/year
• 5th most common cancer in UK; incidence rising steeply
• Median age at diagnosis: ~60 years
• More common in fair-skinned individuals (Fitzpatrick I–II)
• Intermittent intense UV exposure (sunburn) is a stronger risk factor than cumulative exposure

Aetiology

• UV radiation: strongest modifiable risk factor; both UVA and UVB
• Multiple naevi (>100): increased risk
• Dysplastic naevi: atypical mole syndrome increases risk
• Family history: ~10% familial; CDKN2A mutations
• Fair skin: Fitzpatrick types I–II
• Immunosuppression: transplant recipients, HIV
• Previous melanoma: 5–8% lifetime risk of second primary

Pathophysiology

• UV-induced DNA damage (cyclobutane pyrimidine dimers) → oncogenic mutations
• BRAF V600E mutation: ~50% of cutaneous melanoma — constitutive MAPK pathway activation
• NRAS mutations: ~20%
• Radial growth phase → vertical growth phase (invasion) → metastasis
• Immune evasion: PD-L1 upregulation on tumour cells → inhibits T-cell killing

Subtypes

• Superficial spreading (~70%): most common; irregular border, colour variation; radial growth initially
• Nodular (~15%): raised, often uniformly dark or amelanotic; vertical growth from onset (aggressive)
• Lentigo maligna (~10%): face of elderly; slow radial growth; large irregular tan-brown macule
• Acral lentiginous (~5%): palms, soles, nail bed; more common in darker skin types; Hutchinson's sign (nail fold pigmentation)

ABCDE Criteria

• Asymmetry
• Border irregularity
• Colour variation (brown, black, red, white, blue)
• Diameter >6mm
• Evolution (change in any feature)

7-Point Checklist (Glasgow/NICE)

• Major (2 points each): change in size, shape, colour
• Minor (1 point each): diameter ≥7mm, inflammation, oozing/bleeding, change in sensation
• Score ≥3: urgent 2-week wait referral

Red Flags

• Rapidly growing pigmented lesion
• New pigmented lesion in older adult
• Hutchinson's sign (periungual pigmentation)
• Amelanotic (non-pigmented) melanoma — easily missed

Diagnosis

• Dermoscopy: performed by trained clinician; improves diagnostic accuracy by 30%
• Excision biopsy: ALWAYS excise completely with 2mm clinical margin — do NOT incisional biopsy (except large lentigo maligna or acral)
• Histopathology: Breslow thickness, ulceration, mitotic rate, margins, lymphovascular invasion

Staging Investigations (if ≥Stage IIB or node-positive)

• CT thorax/abdomen/pelvis: staging
• MRI brain: if neurological symptoms or stage III–IV
• PET-CT: if advanced disease
• Sentinel lymph node biopsy: if Breslow ≥0.8mm or ulcerated; prognostic staging
• BRAF mutation testing: all stage III–IV melanoma (guides targeted therapy)
• LDH: prognostic marker in advanced disease

Surgical

• Wide local excision with margins based on Breslow thickness:
  • In situ: 5mm
  • ≤1mm: 1cm
  • 1.01–2mm: 1–2cm
  • 2.01–4mm: 2cm

  • 4mm: 2–3cm

• SLNB: if Breslow ≥0.8mm or ulcerated — prognostic; completion lymph node dissection not routinely recommended (DeCOG-SLT, MSLT-II trials)

Adjuvant (Stage III — node-positive)

• Nivolumab (anti-PD-1): 12 months; CheckMate 238 trial — 70% RFS at 4 years
• Pembrolizumab: 12 months; KEYNOTE-054 trial
• Dabrafenib + trametinib: if BRAF V600+ — COMBI-AD trial

Advanced/Metastatic (Stage IV)

• Immunotherapy: nivolumab + ipilimumab (CheckMate 067 — 52% 5-year OS); or single-agent anti-PD-1
• Targeted therapy (BRAF V600+): dabrafenib 150mg BD + trametinib 2mg OD (COMBI-d/v trials — 70% response rate)
• Radiotherapy: brain metastases (stereotactic), symptomatic bony metastases

Follow-Up (NICE NG14)

• Stage IA: discharge with written self-monitoring advice
• Stage IB–IIA: 2–3 monthly for 3 years, then 6-monthly to 5 years
• Stage IIB+: more frequent; include imaging surveillance

Referral Criteria

• 2-week wait: any suspicious pigmented lesion (7-point score ≥3)
• Skin cancer MDT: all confirmed melanoma
• Specialist oncology: stage III–IV for systemic therapy

• Stage I: 5-year survival ~95%
• Stage II: 5-year survival ~65–85%
• Stage III (node-positive): 5-year survival ~40–70%
• Stage IV (metastatic): 5-year survival ~25% (improving with immunotherapy)
• Breslow thickness: strongest prognostic factor (<1mm excellent; >4mm poor)
• Ulceration: independent poor prognostic factor
• Immunotherapy has transformed stage IV prognosis: ipilimumab + nivolumab 5-year OS ~52%

Breslow Thickness and Excision Margins

Melanoma Staging (AJCC 8th Edition)

Landmark Trials in Melanoma