Squamous Cell Carcinoma

Overview

Cutaneous squamous cell carcinoma (SCC) is the second most common form of skin cancer, after basal cell carcinoma. It arises from the uncontrolled proliferation of atypical keratinocytes in the epidermis and may invade surrounding tissues if left untreated. SCC accounts for approximately 20 to 25 percent of all non-melanoma skin cancers.

SCC can develop de novo on sun-damaged skin or may arise from precancerous lesions such as actinic keratoses or Bowen disease (squamous cell carcinoma in situ). While most cutaneous SCCs are detected and treated at an early stage with excellent outcomes, a small proportion may behave aggressively, invading deeper structures or metastasising to regional lymph nodes or distant sites.

Causes and Risk Factors

The primary causative factor for cutaneous SCC is cumulative exposure to ultraviolet (UV) radiation, which induces DNA damage in keratinocytes over time. Both UVA and UVB radiation contribute to carcinogenesis, with UVB playing a particularly significant role in causing direct DNA mutations.

Recognised risk factors for cutaneous SCC include:

• Chronic cumulative sun exposure, particularly in outdoor workers and individuals with a history of repeated sunburns.
• Fair skin, light hair, and blue or green eyes, although SCC can occur in individuals of any skin type.
• Advancing age, with incidence increasing significantly after the age of 50.
• Immunosuppression, including organ transplant recipients on long-term immunosuppressive therapy, who have a markedly elevated risk of developing SCC.
• Pre-existing actinic keratoses or Bowen disease, which represent precursor lesions that may progress to invasive SCC.
• Chronic wounds, scars, or areas of chronic inflammation, which may give rise to SCC (Marjolin ulcer).
• Previous history of skin cancer, including basal cell carcinoma or melanoma.
• Exposure to ionising radiation, arsenic, or certain industrial chemicals.
• Human papillomavirus (HPV) infection, which is implicated in SCC arising in certain anatomical sites.

Signs and Symptoms

Cutaneous SCC typically presents as a firm, pink or red, scaly or crusted nodule or plaque on sun-exposed skin. The most common sites include the face, ears, scalp, neck, forearms, and dorsal hands. The clinical appearance can vary depending on the subtype and stage of the tumour.

Common presentations include:

• A firm, flesh-coloured or reddish nodule that may enlarge over weeks to months.
• A scaly, crusted, or keratotic plaque that does not heal or recurs after treatment.
• An ulcerated lesion with raised, rolled, or indurated borders.
• A rapidly growing, tender, or bleeding skin lesion on a sun-exposed area.
• A cutaneous horn, which is a conical projection of keratin that may overlie an SCC at its base.

Diagnosis

Diagnosis of cutaneous SCC is confirmed through histopathological examination of a tissue biopsy. A dermatologist may perform an incisional, punch, or shave biopsy to obtain a representative sample of the lesion. Dermoscopy is often used as an adjunctive tool to assess the clinical features and guide biopsy decisions.

The histological report provides important information regarding the tumour subtype, depth of invasion, degree of differentiation, and the presence or absence of perineural or lymphovascular involvement, all of which influence treatment planning and prognosis.

Treatment Options

Treatment selection depends on the size, location, depth, and histological subtype of the tumour, as well as patient-specific factors such as immune status and comorbidities.

Surgical Excision

Standard surgical excision with predetermined margins is the most common treatment for cutaneous SCC. The excised tissue is examined histologically to confirm complete removal. Mohs micrographic surgery, which involves the sequential removal and microscopic examination of tissue layers, is indicated for high-risk SCCs, recurrent tumours, and lesions in cosmetically or functionally sensitive areas such as the face, ears, and hands.

Non-Surgical Treatments

For in situ disease (Bowen disease) or superficial, low-risk SCCs, non-surgical options may include cryotherapy, curettage and electrodesiccation, topical therapies (such as 5-fluorouracil or imiquimod), and photodynamic therapy. Radiation therapy may be considered for patients who are not surgical candidates or as adjuvant treatment following excision of high-risk tumours.

Advanced Disease

For locally advanced or metastatic SCC that is not amenable to surgery or radiation, systemic immunotherapy with checkpoint inhibitors (such as cemiplimab or pembrolizumab) has demonstrated significant efficacy and represents an important advancement in the management of advanced cutaneous SCC.

When to Seek Medical Attention

Medical evaluation is recommended for any new, enlarging, non-healing, bleeding, or ulcerating skin lesion, particularly on sun-exposed areas. Individuals with a history of significant sun exposure, prior skin cancer, immunosuppression, or multiple actinic keratoses are at increased risk and should undergo regular skin examinations. Early detection and treatment of SCC significantly improves outcomes and reduces the risk of local recurrence or metastasis.