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Cutaneous Squamous Cell Carcinoma – Causes and Treatment

Cutaneous squamous cell carcinoma is a malignant skin tumor arising from the keratinocytes of the outer skin layer. It is one of the most common forms of skin cancer and can spread to deeper tissues or lymph nodes if left untreated.

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Things worth knowing about "Cutaneous Squamous Cell Carcinoma"

Cutaneous squamous cell carcinoma is a malignant skin tumor arising from the keratinocytes of the outer skin layer. It is one of the most common forms of skin cancer and can spread to deeper tissues or lymph nodes if left untreated.

What is Cutaneous Squamous Cell Carcinoma?

Cutaneous squamous cell carcinoma (cSCC) is a malignant tumor of the skin originating from keratinocytes – the predominant cells of the outer layer of the skin (epidermis). It is the second most common form of skin cancer after basal cell carcinoma, accounting for approximately 20% of all skin cancers. Unlike basal cell carcinoma, cSCC carries a higher risk of spreading to surrounding tissues and, in some cases, forming distant metastases.

Causes and Risk Factors

The development of cutaneous squamous cell carcinoma is influenced by a combination of genetic mutations and environmental factors.

Chronic UV radiation: Long-term exposure to ultraviolet light from sunlight or tanning beds is the primary risk factor, causing DNA damage in skin cells.
Fair skin type: People with light complexions, fair or red hair, and blue eyes are at significantly higher risk.
Precancerous lesions: Actinic keratoses are considered direct precursors to squamous cell carcinoma.
Immunosuppression: Organ transplant recipients and individuals with HIV infection have a markedly elevated risk.
Chronic wounds and scars: Long-standing inflammation or scar tissue can promote tumor development.
Chemical carcinogens: Exposure to arsenic, polycyclic aromatic hydrocarbons, or certain pesticides increases the risk.
Human papillomavirus (HPV): Certain HPV strains are linked to cSCC development, particularly in immunocompromised individuals.

Symptoms

Cutaneous squamous cell carcinoma most commonly appears on sun-exposed areas such as the face, ears, hands, forearms, and lips. Typical signs include:

Firm, scaly, or crusted skin areas that do not heal
Red, raised nodules or plaques
Ulcers or open sores that persist despite treatment
Wart-like growths with a rough surface
Pain, itching, or tendency to bleed in the affected area

Important: Any skin change that persists for more than a few weeks or continues to grow should be evaluated by a doctor promptly.

Diagnosis

Diagnosis is typically established through the following steps:

Clinical examination: A dermatologist visually inspects the lesion for suspicious features.
Dermoscopy: A handheld magnification tool (dermatoscope) allows closer examination of subsurface skin structures.
Biopsy: A tissue sample (biopsy) is taken and analyzed histologically under a microscope to confirm the presence of cancer cells.
Imaging: If metastatic spread is suspected, ultrasound, CT, or MRI scans may be used to assess lymph nodes and internal organs.

Treatment

Treatment depends on the size, location, and extent of the tumor, as well as the overall health of the patient.

Surgical Treatment

Complete surgical excision with adequate safety margins is the standard treatment. Mohs micrographic surgery allows tissue-sparing removal with simultaneous margin control and is especially recommended for tumors on the face or in cosmetically sensitive areas.

Radiation Therapy

For inoperable tumors or as adjuvant therapy after surgery, radiation therapy can be used to eliminate remaining cancer cells.

Systemic and Targeted Therapies

For locally advanced or metastatic disease, the following options are available:

Checkpoint inhibitors (immunotherapy): Agents such as cemiplimab (a PD-1 inhibitor) are approved for advanced cSCC and demonstrate favorable response rates.
Chemotherapy: Systemic chemotherapy may be considered in cases of extensive metastasis.
Targeted therapy: EGFR inhibitors such as cetuximab are used in selected cases.

Topical and Non-Surgical Approaches

For precancerous lesions such as actinic keratoses, topical agents (e.g., 5-fluorouracil or imiquimod cream), cryotherapy, or photodynamic therapy may be applied.

Prevention and Follow-Up

Consistent sun protection through high-SPF sunscreen, protective clothing, and avoiding midday sun exposure are the most effective preventive measures. After treatment, regular follow-up visits with a dermatologist are essential to detect recurrence or new tumors at an early stage.

References

Que, S.K.T., Zwald, F.O., Schmults, C.D.: Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. Journal of the American Academy of Dermatology, 78(2), 237–247 (2018).
World Health Organization (WHO): Skin cancers. Available at: https://www.who.int/news-room/fact-sheets/detail/skin-cancers (2023).
National Comprehensive Cancer Network (NCCN): NCCN Clinical Practice Guidelines in Oncology – Squamous Cell Skin Cancer, Version 2.2024.

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