Malignant melanoma

Overview

•Fitzpatrick skin type I/II (fair skin)

•UV exposure - intermittent intense sun exposure, sunbed use

•Multiple melanocytic naevi / atypical naevi

•Personal or family history of melanoma; CDKN2A mutation

Classification

Melanoma subtypes
FeatureSuperficial spreadingNodularLentigo maligna
FrequencyMost commonSecond most commonLess common
Typical patientAge >40, fairer skinAge >50, fairer skinOlder adults
SiteLegs (women), back (men); intermittent sun exposureHead and neck (chronically exposed)Face, neck, arms; chronic sun exposure
AppearanceFlat pigmented patch, slow radial growth; ABCDE featuresRapidly enlarging dome-shaped nodule, red or black, may bleed/ulcerateSlow-growing flat lesion on chronically sun-exposed skin
Key exam trapClassic ABCDE presentationMay be amelanotic (pink/red); ABCDE criteria less reliableDevelops very slowly - may be overlooked

Feature	Superficial spreading	Nodular	Lentigo maligna
Frequency	Most common	Second most common	Less common
Typical patient	Age >40, fairer skin	Age >50, fairer skin	Older adults
Site	Legs (women), back (men); intermittent sun exposure	Head and neck (chronically exposed)	Face, neck, arms; chronic sun exposure
Appearance	Flat pigmented patch, slow radial growth; ABCDE features	Rapidly enlarging dome-shaped nodule, red or black, may bleed/ulcerate	Slow-growing flat lesion on chronically sun-exposed skin
Key exam trap	Classic ABCDE presentation	May be amelanotic (pink/red); ABCDE criteria less reliable	Develops very slowly - may be overlooked

⚠️
Nodular melanoma does not have a radial growth phase - ABCDE criteria are less reliable. A rapidly enlarging, bleeding, dome-shaped nodule in a fair-skinned patient >50 is nodular melanoma until proven otherwise.

Presentation

•ABCDE criteria:

•A - Asymmetry

•B - Border irregularity (scalloped, notched, ill-defined)

•C - Colour variation (multiple shades of brown, black, red, white, blue)

•D - Diameter >6mm

•E - Evolution (change in size, shape, colour, new itch/bleed/crust)

•Additional red flags: bleeding, ulceration, satellite lesions, regional lymphadenopathy

•Metastatic disease: weight loss, fatigue, hepatomegaly; most common distant sites - liver, lungs, brain, bone

Investigations

•GP role: identify suspicious lesion, apply 2-week-wait criteria, refer urgently - do NOT biopsy in primary care

•Dermoscopy - dermatologist; subsurface visualisation before excision

•Excision biopsy with 2mm margin - gold standard; provides Breslow thickness, mitotic rate, ulceration status, Clark level

•BRAF mutation testing - performed on all confirmed melanomas to guide systemic therapy

•CT chest/abdomen/pelvis ± MRI brain - staging if Breslow >1mm or suspicious lymphadenopathy

•Sentinel lymph node biopsy (SLNB) - offered for Breslow >1mm (or >0.8mm with ulceration); staging and prognostic value

•LDH - elevated in metastatic disease; marker of tumour burden

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Refer urgently (2-week-wait) if any ABCDE feature is present. A lesion with many atypical naevi where the patient may not notice change should still trigger urgent referral if the lesion is suspicious.

Management

•First-line (localised): wide local excision (WLE) - margin guided by Breslow thickness; definitive treatment

•SLNB at time of WLE for Breslow >1mm; if positive, completion lymph node dissection or adjuvant therapy considered

•Adjuvant (resected stage III, any BRAF status): pembrolizumab or nivolumab (anti-PD-1) - reduces recurrence risk

•Adjuvant (resected stage III, BRAF-mutated): dabrafenib + trametinib (BRAF/MEK inhibitor) - alternative option

•Metastatic, BRAF-mutated: vemurafenib or dabrafenib + trametinib - rapid response but resistance often develops

•Metastatic, any BRAF status: pembrolizumab or nivolumab ± ipilimumab (anti-CTLA-4) - durable responses in subset

💡
BRAF mutation (present in ~50% of melanomas) does NOT directly worsen prognosis - it guides therapy choice (BRAF/MEK inhibitors). Surgery remains first-line at all resectable stages.

Prognosis

•Breslow thickness - single most important prognostic factor: depth in mm reflects access to lymphatics/vessels

•Breslow <1mm = excellent prognosis; Breslow >4mm = significantly increased mortality

•Mitotic rate - second most important predictor of mortality (after Breslow thickness)

•Ulceration - independent poor prognostic factor; upstages tumour within T category

•Nodal involvement - positivity upstages to at least stage III; dramatically worsens prognosis

•BRAF mutation - NOT directly prognostic; relevant to therapy choice only

•5-year survival: stage I ~95-99%; stage II ~65-85%; stage III ~40-70%; stage IV ~15-20%

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Prognostic factor ranking: 1. Breslow thickness (most important) 2. Mitotic rate 3. Ulceration 4. Nodal status 5. BRAF mutation status (NOT directly prognostic).