Clinical meaning
Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, arising from malignant transformation of epidermal keratinocytes. Pathogenesis involves cumulative UV radiation damage → DNA mutations (particularly p53 tumor suppressor gene) → progression from actinic keratosis (precursor) → SCC in situ (Bowen disease) → invasive SCC → potentially metastatic SCC. UV-B radiation causes direct DNA damage (thymine dimers), while UV-A generates reactive oxygen species. The progression to invasion involves degradation of the basement membrane by matrix metalloproteinases (MMPs), allowing tumor cells to invade the dermis. Unlike basal cell carcinoma, SCC has significant metastatic potential (2-6% overall; up to 30% for high-risk lesions). Staging uses the AJCC TNM system (8th edition): T1 (<2 cm), T2 (2-4 cm), T3 (>4 cm or minor bone/perineural/deep invasion), T4 (axial skeleton, skull base, or extensive invasion). High-risk features requiring Mohs micrographic surgery referral: location on the face (ears, lips, nose, eyelids, temple), size >2 cm, poorly differentiated histology, perineural invasion (PNI), depth beyond subcutaneous fat, immunosuppressed patient, recurrent tumor, and tumor arising in chronic wound/scar/radiation field. Mohs surgery provides the highest cure rate...