Melanoma
A deadly form of skin cancer that starts in pigment cells, often looking like an irregular, changing mole, and requires surgical removal before it spreads.
Emergency Management: Hemorrhagic brain metastasis causing increased intracranial pressure or uncal herniation; requires emergent neurosurgical decompression and dexamethasone.
Melanoma is an aggressive form of skin cancer arising from the malignant transformation of melanocytes, the pigment-producing cells of the skin. While it accounts for a minority of skin cancer cases, it is responsible for the vast majority of skin cancer deaths due to its high propensity for early metastasis.
Detailed Overview
The disease is primarily driven by ultraviolet (UV) radiation exposure combined with genetic susceptibility. It frequently presents as a new, unusual, or changing mole (the 'ugly duckling'). Prognosis is heavily dependent on the Breslow depth—the microscopic thickness of the tumor. Early-stage melanoma is highly curable with surgical excision, but metastatic melanoma requires complex systemic therapies, including targeted BRAF inhibitors and immune checkpoint inhibitors.
Epidemiology & Demographics
Incidence is rising globally. In the US, it is the 5th most common cancer. Median age of diagnosis is 65, but it is one of the most common cancers in young adults (ages 25-29). Significantly more common in fair-skinned (Caucasian) populations.
Etiological Mechanism
Result of DNA damage primarily from intermittent, intense ultraviolet (UV) radiation (sunburns) in genetically susceptible individuals.
Primary Causes
UV-induced mutations in key oncogenes (BRAF, NRAS) or tumor suppressor genes (CDKN2A, PTEN).
UV radiation causes pyrimidine dimers and oxidative DNA damage in melanocytes. About 50% of melanomas harbor an activating mutation in the BRAF gene (most commonly V600E), leading to constitutive activation of the MAPK/ERK signaling pathway, driving uncontrolled cellular proliferation. The melanoma progresses from radial growth (superficial spreading within the epidermis) to a vertical growth phase (invading the dermis), gaining the ability to enter lymphatic and blood vessels, leading to metastasis to lymph nodes, lungs, brain, and liver.
Diagnostic Criteria & Guidelines
Diagnosis is definitively established by a full-thickness excisional skin biopsy (with 1-3 mm margins) of the suspicious lesion. The pathology report must detail the Breslow thickness, ulceration status, and mitotic rate. Shave biopsies are contraindicated as they may transect the tumor, destroying critical staging information.
For Stage I/II: Wide Local Excision. Surgical margins depend on Breslow depth (1cm margin for ≤1mm depth; 2cm margin for >1mm depth). Sentinel Lymph Node Biopsy (SLNB) is performed for tumors > 0.8mm or those with ulceration.
Second-Line & Adjunctive Therapy
For Stage III/IV (Systemic Therapy): Immune Checkpoint Inhibitors (Anti-PD-1: Pembrolizumab 200mg IV q3w or Nivolumab; Anti-CTLA-4: Ipilimumab). For BRAF V600 positive tumors: Targeted therapy using BRAF/MEK inhibitors (Dabrafenib 150mg PO BID + Trametinib 2mg PO daily).
Surgical & Procedural Management
Completion Lymph Node Dissection (CLND) is sometimes performed if SLNB is positive. Metastasectomy for isolated, resectable distant metastases (e.g., solitary brain or lung lesion).
Patient Counseling & Advice
Emphasize that a history of melanoma severely increases the risk of developing subsequent primary melanomas. First-degree relatives should also be counseled to undergo professional skin checks due to genetic risk.
Follow-Up & Monitoring Schedule
Total body skin exam by a dermatologist every 3-6 months for the first 1-3 years, then annually for life. For high-risk stages, routine imaging (CT/PET) every 6-12 months for 3-5 years.
Preventive Strategies
Primary prevention involves diligent UV protection starting in childhood. Secondary prevention involves regular skin cancer screenings for high-risk individuals.
Highly dependent on stage at diagnosis. Stage I: >99% 5-year survival. Stage III: 63% 5-year survival. Stage IV: Historically dismal (5%), but with modern immunotherapy and targeted therapy, 5-year survival has remarkably improved to over 30-50%.