Melanoma
Exam Tips
- In UK OSCEs, combine ABCDE with the weighted 7-point checklist and explicitly mention the ugly duckling sign.
- State clearly: if melanoma is suspected, do not biopsy in primary care; arrange urgent suspected-cancer referral (2WW).
- Nodular and amelanotic melanoma are common diagnostic traps because they may not fit classic ABCDE pigmentation patterns.
- Quote prognosis using Breslow thickness and nodal status rather than lesion diameter alone.
- For management viva questions, include MDT staging, surgery first for localized disease, and mutation-guided/immunotherapy options for advanced disease.
- Use image-based revision for subtype recognition (DermNet melanoma subtype image sets are high-yield for spot diagnosis practice).
Definition
Melanoma is a malignant neoplasm of melanocytes, most often arising in the skin, with potential to invade the dermis and metastasize via lymphatic and haematogenous routes. It is classified clinically as in situ (epidermis only), invasive (dermal invasion), or metastatic disease, and includes major subtypes such as superficial spreading, nodular, lentigo maligna melanoma, and acral lentiginous melanoma.
Pathophysiology
Melanoma develops through accumulation of UV-related and non-UV genetic damage in melanocytes, leading to dysregulated MAPK/PI3K signalling (commonly involving BRAF, NRAS, or KIT pathways). Many lesions show an initial radial growth phase within the epidermis, then transition to vertical growth with dermal invasion; this increases access to lymphovascular channels and metastatic potential. Tumour thickness (Breslow depth), ulceration, and nodal involvement are key biological markers of aggressive behaviour and prognosis.
Risk Factors
- Previous melanoma, other skin cancer, or atypical/dysplastic naevi
- Family history of melanoma
- Fair skin phenotype (Fitzpatrick I-II), easy burning, red/blonde hair, light eyes, high freckle density
- History of intense intermittent UV exposure and blistering sunburn (especially childhood)
- Large number of naevi or large congenital melanocytic naevus
- Sunbed/tanning bed use (risk increased with repeated sessions, especially >=10)
- Older age (incidence rises with age, peak in elderly groups)
- Outdoor occupational UV exposure
- Immunosuppression
- Inherited cancer-predisposition syndromes (for example xeroderma pigmentosum)
Clinical Features
Symptoms
- Changing pigmented lesion (size, shape, colour, evolving appearance)
- Itch, irritation, tenderness, or altered sensation in a lesion
- Bleeding, crusting, or ulceration
- New rapidly growing nodule (including pink/red amelanotic lesions)
- Systemic features in advanced disease: weight loss, fatigue, cough, headache, night sweats
Signs
- ABCDE pattern: asymmetry, border irregularity, colour variegation, diameter >6 mm, evolution
- Weighted 7-point checklist features: major (change in size, irregular shape, irregular colour); minor (diameter >=7 mm, inflammation, oozing, change in sensation)
- Ugly duckling sign (lesion that looks different from patient’s other moles)
- Superficial spreading melanoma: asymmetrical flat patch/plaque with irregular border and pigmentation
- Nodular melanoma: raised atypical nodule, may ulcerate/bleed; can be amelanotic and lack classic ABCDE cues
- Lentigo maligna melanoma: irregularly pigmented macule/patch on chronically sun-damaged head/neck skin
- Acral lentiginous melanoma: enlarging irregular pigmented lesion on sole/palm/nail unit
- Regional lymphadenopathy on nodal examination in suspicious/advanced cases
- Image reference: review DermNet image atlases for superficial spreading, nodular, lentigo maligna, acral lentiginous, and amelanotic melanoma patterns
Investigations
Management
Lifestyle Modifications
- Strict photoprotection: shade, protective clothing, broad-spectrum sunscreen, avoid midday sun and sunbeds
- Teach skin self-examination (ABCDE + ugly duckling) and prompt re-presentation for change
- Counsel first-degree relatives on melanoma risk awareness and sun-safety behaviours
Pharmacological Treatment
Immune checkpoint inhibitors (adjuvant/unresectable/metastatic, specialist use)
- Pembrolizumab 200 mg IV every 3 weeks or 400 mg every 6 weeks
- Nivolumab 240 mg IV every 2 weeks or 480 mg every 4 weeks
- Ipilimumab 3 mg/kg IV every 3 weeks for 4 doses (commonly in combination protocols)
Use via oncology MDT protocols only. Major safety issues: immune-related colitis, hepatitis, pneumonitis, nephritis, endocrinopathies, severe dermatological toxicity; monitor organ function and withhold/stop for significant toxicity. Avoid live vaccines during significant immunosuppression from toxicity management.
BRAF/MEK targeted therapy for BRAF V600-mutant melanoma
- Dabrafenib 150 mg orally twice daily + trametinib 2 mg orally once daily
- Vemurafenib 960 mg orally twice daily (often combined with cobimetinib 60 mg once daily on days 1-21 of each 28-day cycle)
- Encorafenib 450 mg orally once daily + binimetinib 45 mg orally twice daily
Only if mutation-positive. Key cautions: pyrexia syndrome (especially dabrafenib combinations), cardiomyopathy, ocular toxicity, hepatotoxicity, QT prolongation/photosensitivity (notably vemurafenib), and major CYP-mediated interactions.
Surgical / Interventional
- No routine incisional/shave biopsy in primary care when melanoma is suspected; urgent specialist pathway referral
- Definitive wide local excision after diagnostic biopsy, with margin based on Breslow depth (typical UK practice: in situ 5 mm; <=1 mm 1 cm; 1.01-2 mm 1-2 cm; >2 mm 2 cm)
- Sentinel lymph node biopsy discussion for appropriate intermediate-thickness lesions
- Therapeutic lymph node dissection or metastasectomy in selected patients after MDT review
Complications
- Local recurrence and in-transit metastases
- Regional nodal spread
- Distant metastases (lung, liver, brain, bone, skin/subcutis)
- Neurological complications from brain metastases (seizures, focal deficits, raised ICP)
- Treatment-related severe immune toxicities (checkpoint inhibitors) or targeted-therapy toxicities (e. g, pyrexia, cardiotoxicity, ocular events)
Prognosis
Outcome is stage-dependent and strongly linked to Breslow thickness and nodal status. Early disease has excellent survival (stage I around near-100% 5-year survival), whereas metastatic stage IV disease has markedly poorer survival (around 30% 5-year survival in population data). Most recurrences occur within 3 years, but late relapse can occur; in situ melanoma is usually cured with complete excision.
Sources & References
🏥BMJ Best Practice(6)
💊BNF Drug References(5)
- Binimetinib [Specialist drug][management.pharmacological]
- Cobimetinib [Specialist drug][management.pharmacological]
- Nivolumab with relatlimab [Specialist drug][management.pharmacological]
- Talimogene laherparepvec [Specialist drug][management.pharmacological]
- Vemurafenib [Specialist drug][management.pharmacological]
✅NICE Guidelines(1)
- Melanoma[overview]
📖Textbook References(3)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1677, 1678)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1622, 1623)[context]
- [Williams, Bailey and Love's Short Practice of Surgery] Norman Williams, Christopher Bulstrode, P Ronan O'Connell - Bailey & Love's Short Practice of Surgery 26E (2013, CRC Press) - libgen.li.pdf(pp. 148)[context]