DermatologyTier 1Disease (DEADMAN)

Cutaneous oncology - melanoma

Description

Malignant proliferation of melanocytes - most lethal common skin cancer despite lower incidence than BCC/SCC
Subtypes: superficial spreading (~70%, commonest), nodular (more aggressive, vertical growth from onset, no radial phase - easily missed), lentigo maligna (chronic sun-damaged skin, elderly, slow radial growth), acral lentiginous (palms/soles/nail bed - not UV-related, relatively commoner in darker skin)
Breslow thickness is the single strongest prognostic factor

Australia has the highest melanoma incidence in the world
Rising incidence with age, but one of the commonest cancers in young adults
Slight male predominance overall; site differs by sex (trunk in men, lower limb in women)

Intermittent intense UV exposure (esp. childhood sunburn) - main driver, more than cumulative dose (contrast with SCC)
BRAF V600 mutation (~40-50%) - actionable, targetable with BRAF/MEK inhibitors
Other driver mutations: NRAS, NF1, KIT (mucosal/acral subtypes)
Risk factors: fair skin (Fitzpatrick I-II), high naevus count, dysplastic naevus syndrome, FHx melanoma (CDKN2A mutation in familial cases), prior melanoma, immunosuppression

Clinical

ABCDE criteria: Asymmetry, Border irregularity, Colour variegation, Diameter >6mm, Evolution (most sensitive single feature)
"Ugly duckling" sign - lesion that looks different from the patient's other naevi
Dermoscopy improves diagnostic accuracy in trained hands

Histology - excisional biopsy is diagnostic standard

Never shave/punch biopsy a suspected melanoma - compromises Breslow thickness measurement, the key staging determinant
Report: Breslow thickness (mm), ulceration (present = worse prognosis, upstages), mitotic rate, margins

AJCC 8th ed staging (T-category by thickness + ulceration)

Ulceration upstages each T-category (e.g. T1b vs T1a)
Sentinel lymph node biopsy - offered for T1b and above (thickness >0.8mm or ulcerated) to stage the regional basin; does not improve overall survival but guides prognosis/adjuvant therapy eligibility

A. Primary excision - wide local excision margins by Breslow thickness

B. Nodal disease

Positive sentinel node - completion lymph node dissection no longer routine (replaced by nodal ultrasound surveillance, per MSLT-II) unless clinically involved nodes
Clinically palpable nodal disease - therapeutic lymph node dissection

C. Adjuvant systemic therapy (resected stage IIB-IV, high recurrence risk)

Anti-PD-1 (nivolumab or pembrolizumab) - now extended to high-risk resected stage IIB/IIC as well as III/IV, ~12 months
BRAF/MEK inhibitor (dabrafenib/trametinib) - alternative for BRAF V600-mutant resected stage III

D. Unresectable/metastatic disease

Combination immune checkpoint inhibition (ipilimumab + nivolumab, or nivolumab + relatlimab) - higher response than monotherapy, more toxicity
BRAF/MEK inhibitor combination - faster response, useful for BRAF-mutant disease with high tumour burden/symptomatic disease pending immunotherapy response
Isolated limb infusion/perfusion or intralesional talimogene laherparepvec (T-VEC) for in-transit/unresectable cutaneous metastases

E. Surveillance

Regular skin checks (self and clinician), risk-stratified imaging surveillance for stage IIB and above

Dysplastic naevus syndrome, high total naevus count
Familial melanoma (CDKN2A, CDK4 mutations) - multiple primary melanomas, pancreatic cancer risk in CDKN2A families
Xeroderma pigmentosum (DNA repair defect)
Immunosuppression (transplant recipients) - higher incidence and more aggressive course

Prognosis tightly linked to Breslow thickness and ulceration at diagnosis - 5-year survival >95% for thin node-negative disease, falling substantially with nodal/distant spread
Metastatic pattern: regional nodes -> skin/subcutaneous (in-transit) -> lung -> liver/brain/bone
Checkpoint inhibitors have transformed metastatic disease prognosis - durable long-term responses now seen in a meaningful minority, a marked shift from pre-2011 outcomes
Lifelong surveillance - risk of second primary melanoma elevated after a first diagnosis

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