Squamous Cell Carcinoma

What Is Squamous Cell Carcinoma?

Squamous cell carcinoma (SCC) is the second most common form of skin cancer, with over 1 million new cases diagnosed in the United States each year. It develops in squamous cells — the flat cells that make up most of the outer layer of skin (epidermis).

Unlike basal cell carcinoma, SCC carries a real but manageable risk of spreading to nearby lymph nodes or other organs, particularly when diagnosis is delayed or when it arises in high-risk locations. The vast majority of SCCs are cured when treated promptly. Untreated or advanced SCC accounts for the majority of the approximately 15,000 skin cancer deaths that are not melanoma each year in the US.

Symptoms

SCC often develops from precancerous lesions called actinic keratoses (rough, scaly patches caused by sun damage). Signs of SCC include:

• Firm, red nodule: On the face, lips, ears, neck, hands, or forearms
• Flat, crusty lesion with a depressed center that may bleed
• Wart-like growth that may crust or bleed
• Open sore that doesn't heal, or heals and then returns
• Rough, scaly patch on the lip that may evolve into an open sore
• Red sore or rough patch inside the mouth
• Wart-like growth on or in the anus or genitals

SCC in situ (Bowen's disease) is a superficial, early form that hasn't yet invaded deeper skin layers — it looks like a red, scaly, well-defined patch and is highly curable.

Causes & Risk Factors

Like basal cell carcinoma, SCC is primarily caused by cumulative UV radiation damage to the DNA of squamous cells. Risk factors include:

• Chronic sun exposure: Decades of outdoor work or recreation, particularly in sunny climates
• History of actinic keratoses: AKs are direct precursors to SCC
• Fair skin and light coloring
• Personal or family history of skin cancer
• Immunosuppression: Transplant patients on immunosuppressive drugs have up to 100× the normal risk of SCC
• Human papillomavirus (HPV): Certain HPV strains are associated with SCC in the genital area and under fingernails
• Chronic wounds or scars: SCC can arise in areas of chronic inflammation or injury (Marjolin's ulcer)
• Chemical exposure: Arsenic, industrial chemicals
• Radiation therapy: Prior therapeutic radiation to the skin

Diagnosis

Diagnosis follows the same path as other skin cancers:

1. Clinical and dermoscopic examination by a dermatologist
2. Biopsy: A shave, punch, or excisional biopsy is sent for pathologic review
3. Staging evaluation: For high-risk or advanced lesions, imaging (ultrasound, CT) may be used to assess lymph node involvement

High-risk features that increase the likelihood of recurrence or spread include: location on the ear, lip, or scalp; diameter greater than 2cm; depth greater than 2mm; poorly differentiated cells on pathology; perineural invasion; immunosuppressed patient.

Treatment Options

• Surgical excision: Standard treatment for most SCCs, with margins guided by tumor size and risk category. Cure rates exceed 95% for low-risk tumors.
• Mohs micrographic surgery: Preferred for high-risk or recurrent SCCs, especially on the face, ears, and lips. Offers the highest cure rate while preserving maximum healthy tissue.
• Electrodessication and curettage (ED&C): Appropriate for small, low-risk, superficial SCCs on the trunk and extremities
• Radiation therapy: For patients who cannot undergo surgery, or as adjuvant treatment for high-risk features
• Topical treatments: 5-fluorouracil or imiquimod for SCC in situ (Bowen's disease)
• Systemic therapy: For metastatic SCC, anti-PD-1 immunotherapy (cemiplimab) has shown significant efficacy

Prevention

• Daily broad-spectrum SPF 30+ sunscreen, reapplied every two hours when outdoors
• Protective clothing and hats
• Avoid peak UV hours (10 AM–4 PM)
• Treat actinic keratoses promptly — AKs that progress to SCC are preventable
• Monthly self-checks and annual full-body skin exams
• For high-risk patients (transplant recipients, history of multiple SCCs): more frequent monitoring, possibly every 3–6 months

When to See a Doctor

Any scaly, rough, or persistent lesion on sun-exposed skin deserves evaluation — especially if it has been present for more than a few weeks without healing. SCC arising from a longstanding actinic keratosis can be subtle at first.

See a dermatologist promptly if:

• A lesion bleeds easily or won't heal
• A previously treated AK changes or grows
• Any new bump, sore, or scaly patch appears on sun-damaged skin
• You notice swollen lymph nodes near a skin lesion

References

1. Rogers HW, Weinstock MA, Feldman SR, Coldiron BM. Incidence estimate of nonmelanoma skin cancer (keratinocyte carcinomas) in the US population, 2012. JAMA Dermatology. 2015;151(10):1081–1086. doi:10.1001/jamadermatol.2015.1187
2. American Academy of Dermatology Association. Squamous cell carcinoma: Overview. aad.org
3. Que SKT, Zwald FO, Schmults CD. Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. Journal of the American Academy of Dermatology. 2018;78(2):237–247. doi:10.1016/j.jaad.2017.08.059
4. Alam M, Ratner D. Cutaneous squamous-cell carcinoma. New England Journal of Medicine. 2001;344(13):975–983. doi:10.1056/NEJM200103293441306
5. Migden MR, Rischin D, Schmults CD, et al. PD-1 blockade with cemiplimab in advanced cutaneous squamous-cell carcinoma. New England Journal of Medicine. 2018;379(4):341–351. doi:10.1056/NEJMoa1805131
6. National Comprehensive Cancer Network. Squamous Cell Skin Cancer (Version 2.2024). nccn.org
7. Karia PS, Han J, Schmults CD. Cutaneous squamous cell carcinoma: estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. Journal of the American Academy of Dermatology. 2013;68(6):957–966. doi:10.1016/j.jaad.2012.11.037