Non-melanoma Cancer of the skin

Non-melanoma skin cancers are the most common malignant tumors of the skin and primarily include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Basal cell carcinoma is the most frequently occurring type and is generally slow-growing with a low metastatic potential. Squamous cell carcinoma is more aggressive and has the potential to invade locally and metastasize to regional lymph nodes and distant sites.

The primary cause of non-melanoma skin cancers is prolonged exposure to ultraviolet (UV) radiation. Early detection and treatment are associated with excellent outcomes, particularly when lesions are identified before local invasion or metastasis occurs.

Epidemiology

Non-melanoma skin cancers are among the most common cancers worldwide. They occur more frequently in individuals with prolonged sun exposure and in populations with lighter skin pigmentation. People with albinism are at particularly high risk because of reduced skin pigmentation and increased susceptibility to ultraviolet radiation damage.

Risk factors

Risk factors for non-melanoma skin cancers include:

• Excessive exposure to ultraviolet radiation.

• Light-colored skin.

• Albinism.

• Previous burn scars.

• Chronic skin injury.

• Immunosuppression.

• HIV infection.

• Organ transplantation.

• Increasing age.

• Previous history of skin cancer.

Pathophysiology

Basal cell carcinoma

Basal cell carcinoma arises from basal cells of the epidermis. It is characterized by slow growth and local tissue invasion but rarely metastasizes.

Squamous cell carcinoma

Squamous cell carcinoma originates from keratinizing epidermal cells. It is more aggressive than basal cell carcinoma and may invade deeper tissues, involve regional lymph nodes, and metastasize to distant organs.

Chronic ultraviolet radiation exposure causes cumulative DNA damage, resulting in malignant transformation of skin cells.

Clinical presentation

Patients commonly present with a persistent skin lesion on sun-exposed areas. Lesions may gradually enlarge, ulcerate, bleed, or fail to heal despite treatment.

Symptoms

• Persistent skin lesion.

• Non-healing ulcer.

• Slowly enlarging skin growth.

• Bleeding skin lesion.

• Pain in advanced disease.

• Symptoms related to local invasion.

• Symptoms related to metastatic disease in advanced squamous cell carcinoma.

Clinical signs

• New skin growth on exposed skin.

• Non-healing ulcer.

• Nodular lesion.

• Ulcerated lesion.

• Crusted skin lesion.

• Changes in the appearance of existing skin lesions.

• Lesions arising within old burn scars.

• Regional lymphadenopathy in advanced disease.

• Signs of bone involvement in advanced disease.

Differential diagnosis

Conditions that may mimic non-melanoma skin cancers include:

• Chronic skin ulcers.

• Actinic keratosis.

• Keratoacanthoma.

• Cutaneous tuberculosis.

• Chronic fungal infections.

• Pyogenic granuloma.

• Viral warts.

• Chronic traumatic ulcers.

• Hypertrophic scars.

• Keloids.

• Melanoma.

• Kaposi sarcoma.

Diagnostic criteria

Non-melanoma skin cancer should be suspected in patients with:

• A new skin growth on sun-exposed skin.

• A persistent non-healing ulcer.

• Progressive changes in the appearance of a skin lesion.

• A lesion arising in an old burn scar.

• A lesion that bleeds, enlarges, or recurs after treatment.

Definitive diagnosis requires histopathological confirmation.

Investigations

Small lesions

• No additional investigations may be required before definitive excision.

Imaging investigations

• Local X-ray if bone involvement is suspected.

• Chest X-ray (CXR).

• Computed tomography (CT) scan for suspected nodal or bone involvement.

• Magnetic resonance imaging (MRI) for suspected nodal or bone involvement.

• Positron emission tomography/computed tomography (PET/CT) when indicated.

Histopathological investigations

• Biopsy of the lesion.

• Excisional biopsy is preferred whenever feasible.

Management

Management depends on tumor type, size, anatomical location, depth of invasion, nodal involvement, and patient factors.

Surgery remains the primary treatment for most patients.

Non-pharmacological treatment

Surgical treatment

The primary treatment is:

• Wide local excision with negative surgical margins.

Additional procedures may include:

• Skin grafting following excision when required.

Locally destructive procedures

Selected lesions may be managed using:

• Curettage.

• Cryotherapy.

Palliative surgery

In advanced disease:

• Amputation may be considered for palliation in selected patients.

Radiotherapy

Radiotherapy is indicated for:

• Positive surgical margins.

• High-grade disease.

• Inoperable tumors.

Radical radiotherapy

• External beam radiotherapy (EBRT) 60–66 Gy in 30–33 fractions.

Palliative radiotherapy

• 30 Gy in 10 fractions.

Pharmacological treatment

Topical therapy

For very superficial lesions or carcinoma in situ:

5-Fluorouracil topical cream

• Apply topically every 12–24 hours.

Systemic therapy

Systemic chemotherapy may be used:

• For palliation in advanced disease.

• As a radiosensitizer during radiotherapy.

Management according to underlying cause

Basal cell carcinoma

• Wide local excision with negative margins.

• Curettage or cryotherapy for selected lesions.

• Radiotherapy for inoperable disease or positive margins.

Squamous cell carcinoma

• Wide local excision with negative margins.

• Assessment for regional lymph node involvement.

• Radiotherapy for high-grade disease, positive margins, or inoperable tumors.

• Palliative treatment for advanced metastatic disease.

Skin cancer associated with albinism

• Early diagnosis and treatment.

• Strict avoidance of ultraviolet exposure.

• Regular skin surveillance.

Skin cancer associated with immunosuppression

• Prompt evaluation of suspicious lesions.

• Early definitive treatment.

• Close follow-up due to increased risk of recurrence.

Referral

Patients should be referred to a specialist center when:

• Histological confirmation of malignancy is obtained.

• Lesions are large or locally advanced.

• Bone involvement is suspected.

• Regional lymph node involvement is present.

• Reconstructive surgery is required.

• Radiotherapy is indicated.

• Metastatic disease is suspected.

Urgent referral is recommended for patients with rapidly growing lesions, suspected squamous cell carcinoma, or evidence of metastatic spread.

Complications

• Local tissue destruction.

• Cosmetic deformity.

• Chronic ulceration.

• Secondary infection.

• Bone invasion.

• Regional lymph node metastasis.

• Distant metastasis, particularly in squamous cell carcinoma.

• Recurrence after treatment.

• Functional impairment depending on tumor location.

Prognosis

The prognosis is generally excellent when lesions are detected and treated early. Basal cell carcinoma rarely metastasizes and has a high cure rate with complete excision. Squamous cell carcinoma has a higher risk of recurrence and metastasis, particularly in advanced disease, immunosuppressed patients, and tumors arising from chronic scars or burns.

Prevention

• Avoid excessive ultraviolet radiation exposure.

• Use protective clothing and sun protection measures.

• Regular self-examination of the skin.

• Early evaluation of suspicious skin lesions.

• Prompt treatment of premalignant and early malignant lesions.

• Regular screening of high-risk individuals.

• Strict sun protection for individuals with albinism.

• Early management of chronic wounds and burn scars.

• Regular follow-up for immunocompromised patients.