Cutaneous squamous cell carcinoma is the second most common skin cancer in fair-skinned populations, with an estimated 1.8 million US cases diagnosed annually (Rogers 2015 incidence study). It arises from epidermal keratinocytes after cumulative ultraviolet damage, and most lesions concentrate on chronically sun-exposed skin: the face, ears, scalp, dorsa of the hands, and lower lip.
Cutaneous squamous cell carcinoma (cSCC) (ICD-10: C44) is a malignancy of epidermal keratinocytes characterized by atypical squamous proliferation that invades the dermis. It is the second most common non-melanoma skin cancer after basal cell carcinoma, accounting for approximately 20-25% of cutaneous malignancies in fair-skinned populations. Cumulative ultraviolet radiation drives the disease through characteristic UV-signature mutations in tumor-suppressor genes — TP53 (over 90% of cases), NOTCH1, CDKN2A — accumulated over decades of sun exposure. Most cSCCs arise within fields of actinic keratosis, the recognized precursor lesion that progresses to invasive SCC at a rate of 0.1-1% per lesion per year.
The key symptoms of Squamous Cell Carcinoma are: A scaly, hyperkeratotic, often tender nodule or plaque on sun-exposed skin that enlarges over weeks to months, sometimes with a thick crust or ulcerated surface., A non-healing sore that bleeds with minimal trauma, scabs over, partially heals, and breaks down again — any such lesion present beyond 4-6 weeks warrants biopsy., An indurated, firm, fixed nodule with a rough or warty surface, often arising within a field of pre-existing actinic keratoses or chronic sun-damaged skin., A rapidly enlarging dome-shaped nodule with a central keratin-filled crater (keratoacanthoma) — clinically resembles a low-grade SCC and is now classified as such., A red, scaly, well-demarcated patch on the trunk, scalp, or genitalia that resembles eczema or psoriasis but does not respond to topical steroids — typical of SCC in situ (Bowen disease)., Pain, tenderness, or burning at the lesion site, particularly when there is perineural invasion of cutaneous sensory branches., Numbness, paresthesia, or muscle weakness adjacent to a long-standing facial SCC — perineural invasion of branches of the trigeminal or facial nerves is a critical red flag..
Diagnosis of cutaneous squamous cell carcinoma begins with clinical inspection and dermatoscopy. Dermatoscopic features include white scales, looped or coiled vessels, blood spots, central white-yellow structureless areas, and ulceration — these reach over 90% accuracy in trained hands. Skin biopsy is mandatory for any suspicious lesion. Punch biopsy (4 mm) provides full-thickness tissue including depth, which is essential for AJCC and Brigham and Women's Hospital staging. Shave biopsy is acceptable for clearly superficial lesions but may underestimate depth. Histology identifies the variant (conventional, acantholytic, desmoplastic, verrucous, in situ) and grade (well, moderately, poorly differentiated). High-risk features that drive treatment intensification include diameter over 2 cm, depth over 6 mm or invasion beyond subcutaneous fat, perineural invasion of nerves over 0.1 mm, location on the ear or lip, immunosuppression, recurrent disease, and poor differentiation. Per the NCCN Squamous Cell Skin Cancer Guidelines, high-risk lesions warrant Mohs micrographic surgery and may require sentinel lymph node biopsy or imaging. MRI of the affected region assesses perineural spread, depth, and bone involvement in high-risk tumors. CT and PET/CT are used for nodal staging in clinically advanced disease. Ultrasound of regional nodal basins detects clinically silent metastases in high-risk lesions. Genomic profiling and circulating tumor DNA testing are emerging tools in advanced disease. The differential diagnosis includes basal cell carcinoma, keratoacanthoma (now classified as a variant of SCC), actinic keratosis, seborrheic keratosis, amelanotic melanoma, Merkel cell carcinoma, and benign keratoses. Histology resolves uncertainty in all cases.
Prognosis depends heavily on stage and risk classification. Low-risk early-stage cSCC carries a 5-year cure rate over 95% with appropriate surgical treatment, and overall mortality remains under 1%. High-risk cSCC (over 2 cm, deep invasion, perineural involvement, ear or lip location, immunosuppression) has a 5-year local recurrence rate of 10-25% and a metastatic risk of 5-15%. Patients with regional nodal involvement have 5-year survival of 25-40%; distant metastatic disease falls to 10-20% historically, though cemiplimab now achieves durable responses in roughly half of treated patients (median response duration over 24 months in EMPOWER-CSCC-1). Brigham and Women's Hospital T2b/T3 tumors carry 50% 5-year recurrence and metastatic risks combined; the Karia 2013 staging study formalized these predictors. Transplant recipients face dramatically worse outcomes, with multiple aggressive tumors and 8% mortality from cSCC despite optimal care. The dominant long-term issue for most patients is recurrence and second-primary cSCC — 30-50% of patients develop a new NMSC within 5 years. Lifelong dermatologic surveillance, strict photoprotection, and chemoprevention with nicotinamide or acitretin are the standard of care.
Any persistent, scaly, non-healing, or rapidly enlarging skin lesion warrants dermatologist evaluation. Mohs micrographic surgeons should manage high-risk cSCC on the face, head, neck, ear, and lip, as well as recurrent disease, tumors over 2 cm, and lesions with aggressive histology. Multidisciplinary head-and-neck cancer teams and medical oncologists coordinate care for advanced or metastatic disease, particularly when systemic immunotherapy is indicated.
Find specialists →Wound healing after Mohs or excisional surgery takes 2-4 weeks for primary closure and 4-8 weeks for skin grafts or local flaps. Sutures are removed at 5-7 days on the face and 10-14 days on the trunk. Scar maturation continues for 6-12 months. Adjuvant radiation typically completes over 5-6 weeks with side effects (skin reaction, fatigue) lasting 2-4 weeks beyond the last treatment. Cemiplimab and pembrolizumab responses appear over 2-4 months and may continue beyond 24 months in responders. Return to daily activities is usually within 1-2 weeks after outpatient surgery; major reconstructive procedures require 4-8 weeks.
Regular exercise (150 minutes weekly of moderate activity) supports general health. Outdoor exercise should pair with strict photoprotection — long sleeves, wide-brimmed hat, sunscreen, and timing outside peak UV hours. Indoor activity (swimming pools with sun protection, gyms) avoids UV entirely. Resume normal activity 1-2 weeks after outpatient surgery; 4-6 weeks after reconstructive surgery.
Look for board certification in dermatology and, for high-risk facial cSCC, fellowship training in Mohs micrographic surgery (American College of Mohs Surgery certification). For advanced disease, seek NCI-designated cancer centers offering cemiplimab and pembrolizumab access plus clinical trials. Transplant recipients should receive specialized transplant dermatology follow-up every 3-6 months.
Medically reviewed by AIHealz Medical Editorial Board · May 13, 2026
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