Clinical meaning
Cutaneous melanoma arises from malignant transformation of melanocytes, the pigment-producing cells in the stratum basale of the epidermis. Melanoma accounts for only 4% of skin cancers but causes 80% of skin cancer deaths due to its aggressive metastatic potential.
Melanoma subtypes include: superficial spreading melanoma (70% — most common, radial growth phase with lateral spread before vertical invasion), nodular melanoma (15% — most aggressive, lacks radial growth phase, presents as rapidly growing raised nodule with early vertical invasion), lentigo maligna melanoma (10% — arises on chronically sun-damaged skin in elderly, face/neck, slow progression from lentigo maligna in situ), and acral lentiginous melanoma (5% in Caucasians, most common subtype in darker-skinned individuals — palms, soles, nail beds; Bob Marley died of undiagnosed acral melanoma).
Breslow depth is the SINGLE MOST IMPORTANT prognostic factor — it measures tumor thickness in millimeters from the granular layer of the epidermis to the deepest point of tumor invasion. The 2018 AJCC 8th edition staging uses Breslow depth thresholds: T1 (≤1.0 mm), T2 (1.01-2.0 mm), T3 (2.01-4.0 mm), T4 (>4.0 mm). Ulceration upstages the T classification (e.g., T1b = ≤1.0 mm with ulceration, has worse prognosis than T2a = 1.01-2.0 mm without ulceration).
Clark level (depth of invasion by anatomical layer — epidermis through subcutis) has been largely replaced by Breslow depth for staging but remains relevant for thin melanomas (≤1.0 mm).
Sentinel lymph node biopsy (SLNB) is recommended for melanomas >0.8 mm Breslow depth or ≤0.8 mm with ulceration or high mitotic rate, as it provides the most accurate N staging and guides adjuvant therapy decisions. BRAF mutation testing is performed on stage III/IV melanomas because ~50% harbor BRAF V600E mutations, making them candidates for targeted therapy (vemurafenib, dabrafenib) and combination therapy (BRAF + MEK inhibitor).