Clinical meaning
Skin cancer is the most common malignancy worldwide, with three primary types: basal cell carcinoma (BCC — 80% of skin cancers), squamous cell carcinoma (SCC — 16%), and melanoma (4% but responsible for 75% of skin cancer deaths). BCC arises from basal keratinocytes in the epidermis, driven by aberrant Hedgehog signaling pathway activation (PTCH1 gene mutations). It is locally invasive but almost never metastasizes (<0.1%). Classic subtypes include nodular (pearly, translucent papule with telangiectasia and rolled borders — most common), superficial (thin, scaly erythematous patch), morpheaform/sclerosing (waxy, scar-like plaque — most aggressive subtype, difficult to determine margins), and pigmented (brown/black — can mimic melanoma). SCC arises from malignant transformation of epidermal keratinocytes, typically in a stepwise progression from actinic keratosis (precancerous) → SCC in situ (Bowen disease) → invasive SCC. Risk factors include cumulative UV exposure, immunosuppression (organ transplant recipients have 65-250x increased SCC risk), and HPV infection. SCC has 2-5% metastatic potential, higher in immunosuppressed patients and certain anatomic locations (lip, ear, non-sun-exposed sites). Melanoma arises from malignant melanocytes and is classified by subtype: superficial spreading (most common — 70%), nodular (most aggressive — rapid vertical growth), lentigo maligna (sun-damaged skin in elderly), and acral lentiginous (palms, soles, nails — most common type in dark-skinned individuals, often diagnosed late). Melanoma staging uses the AJCC TNM system with Breslow depth (tumor thickness in mm) as the most important prognostic factor: <1 mm = 95% 5-year survival; >4 mm = 45%. The ABCDE criteria guide clinical screening: Asymmetry, Border irregularity, Color variation, Diameter >6 mm, and Evolution (changing).