Related Subjects:
|Nikolsky's sign
|Koebner phenomenon
|Erythema Multiforme
|Pyoderma gangrenosum
|Erythema Nodosum
|Dermatitis Herpetiformis
|Lichen Planus
|Acanthosis Nigricans
|Acne Rosacea
|Acne Vulgaris
|Alopecia
|Vitiligo
|Urticaria
|Basal Cell Carcinoma
|Malignant Melanoma
|Squamous Cell Carcinoma
|Mycosis Fungoides (Sezary Syndrome)
|Xeroderma pigmentosum
|Bullous Pemphigoid
|Pemphigus Vulgaris
|Seborrheic Dermatitis
|Pityriasis/Tinea versicolor infections
|Pityriasis rosea
|Scabies
|Dermatomyositis
|Toxic Epidermal Necrolysis
|Stevens-Johnson Syndrome
|Atopic Eczema/Atopic Dermatitis
|Psoriasis
⚠️ Any lesion suspicious for melanoma → check regional lymph nodes, perform a brief systemic exam, and refer urgently via the 2-week wait suspected cancer pathway.
📖 About Malignant Melanoma
- Malignant melanoma is a malignancy of melanocytes, the pigment-producing cells derived from neural crest.
- Accounts for ~2,300 deaths annually in the UK. Early diagnosis is critical: thin melanomas (<1 mm) have >95% cure rate.
- Incidence is rising, with ~50% of melanomas arising de novo rather than in pre-existing naevi.
- Melanocytes are present in the epidermis, uveal tract, mucous membranes, inner ear, and leptomeninges → rare sites of melanoma include eye, oral cavity, and CNS.
🧬 Background Pathophysiology & Molecular Biology
- Cell of origin: melanocytes are neural crest-derived pigment cells producing melanin in melanosomes.
- UV radiation: causes DNA damage (cyclobutane pyrimidine dimers) leading to mutations in oncogenes and tumour suppressor genes.
- Genetic mutations:
- BRAF V600E/K mutations (~50%) → constitutive MAPK/ERK pathway activation → uncontrolled proliferation
- NRAS mutations (~15–20%) → MAPK and PI3K pathway activation
- c-KIT mutations → more common in acral and mucosal melanoma
- Loss-of-function mutations in CDKN2A (p16) → loss of cell cycle control
- Immune evasion: melanoma expresses PD-L1 and CTLA-4 ligands to inhibit cytotoxic T-cell activity → basis for checkpoint inhibitor therapy.
- Tumour microenvironment: includes stromal fibroblasts, regulatory T-cells, tumour-associated macrophages, and angiogenesis → supports invasion and metastasis.
- Metastatic spread: occurs via lymphatics (regional nodes) and hematogenous routes (lung, liver, brain, bone).
⚡ Risk Factors
- Genetic predisposition: familial melanoma, CDKN2A mutations, dysplastic naevus syndrome
- UV exposure: intermittent sunburn, tanning bed use
- Phenotypic: fair skin, freckles, red/blonde hair, light eye colour, poor tanning ability
- Large number of melanocytic naevi (>50), atypical naevi, congenital naevi
- Older age and male sex (poorer prognosis)
- Rare syndromes: xeroderma pigmentosum, immunosuppression (organ transplant, HIV)
👀 Clinical Features
- New or changing pigmented lesion, often irregular in shape, colour, or elevation
- ABCDE features:
- A – Asymmetry: one half ≠ other half
- B – Border: irregular, scalloped, or poorly defined
- C – Colour: variegated: brown, black, pink, blue, red
- D – Diameter: >6 mm (can be smaller)
- E – Evolution: rapid changes, ulceration, bleeding, or new nodularity
- May present as nodular, acral, lentigo maligna, or superficial spreading subtypes
- Regional lymph node enlargement may occur with metastasis
📏 Breslow Depth & Prognosis
- Measured from epidermal granular layer to deepest malignant cell
- Predicts risk of metastasis and survival
- Adjunctive prognostic features: ulceration, mitotic rate, lymphovascular invasion
🔬 Investigations
- Excisional biopsy for diagnosis and Breslow measurement
- Wide local excision (WLE) guided by depth
- Sentinel lymph node biopsy for tumours ≥1 mm or thinner high-risk tumours
- Staging imaging for advanced disease: CT, PET-CT, MRI, or ultrasound
- Blood tests: LDH, liver function tests, full blood count if systemic disease suspected
💊 Management Overview
- Wide local excision with margins determined by Breslow thickness
- Sentinel node biopsy where indicated
- Adjuvant therapy for high-risk or stage III–IV disease:
- Checkpoint inhibitors (anti-PD-1: nivolumab, pembrolizumab; anti-CTLA-4: ipilimumab)
- BRAF + MEK inhibitors for BRAF-mutant tumours (dabrafenib + trametinib, vemurafenib + cobimetinib)
- Radiotherapy or palliative surgery for unresectable metastases
- Experimental therapies: vaccines, novel immunotherapies in trials
📚 Key UK Guidance References
