Squamous cell carcinoma of the skin (spinocellular carcinoma, SCC)

Squamous cell carcinoma, spinalioma, epithelioma spinocellulare, spinocellular carcinoma, keratinizing squamous cell carcinoma of the skin, prickle cell carcinoma, spindle cell carcinoma, verrucous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (SCC) is a malignant epithelial tumor originating from keratinocytes of the stratum spinosum. It exhibits invasive growth potential and may metastasize via lymphatic and less commonly hematogenous routes. It frequently arises from actinic keratoses or other premalignant skin lesions.

In Switzerland, SCC is the second most common skin cancer in fair-skinned individuals after basal cell carcinoma. The incidence is approximately 40–50/100,000/year, with a marked increase among the elderly. Men are affected about twice as often as women. The average age of onset is above 70 years. Immunosuppressed patients (e.g., transplant recipients) have up to a 200-fold increased risk.

Histological subtypes (WHO 2023):

• Classical (keratinizing) SCC
• Spindle cell SCC (aggressive behavior)
• Acantholytic SCC
• Verrucous SCC (favorable prognosis)
• Clear cell SCC
• Mucin-secreting SCC
• Lymphoepithelioma-like SCC
• SCC with horn formation
• Broders grading: G1–G4 depending on the degree of differentiation

Precancerous / in situ lesions:

• Actinic keratosis
• Bowen’s disease (intraepidermal SCC)
• Erythroplasia of Queyrat
• Actinic cheilitis
   

The main cause is chronic UV exposure, particularly UV-B. Additional risk factors include:

• Fair skin phototype (Fitzpatrick I–II)
• Immunosuppression
• Genodermatoses (e.g., xeroderma pigmentosum)
• HPV infection (types 16, 18 in anogenital SCC)
• Chronic inflammatory or scarring dermatoses
• Chemical carcinogens (arsenic, tar, soot)
• Ionizing radiation
• Smoking, alcohol abuse
• Occupational exposure (construction, agriculture, roofing)

Typically presents as a firm, scaly, erythematous plaque or nodule, often hyperkeratotic and exophytic. Ulceration or horn-like keratosis (cutaneous horn) may occur. Lesions are usually painless. Verrucous types have a wart-like surface. Advanced disease may lead to perineural invasion and regional lymph node metastases.

• Clinical examination and detailed history
• Histological confirmation via biopsy
• Dermoscopy
• Once confirmed: full skin examination and regional lymph node palpation
• Staging (UICC 8) using ultrasound, CT/MRI or PET-CT in high-risk cases
• AJCC classification considers tumor size, depth, perineural invasion

80–90 % of cutaneous SCCs occur in UV-exposed areas, particularly the head and neck. Other sites: dorsal hands, forearms, lower legs. Mucosal (oral, genital) and periungual lesions are rarer but more aggressive.

Chronic sun exposure (occupational, tanning beds), history of actinic keratoses or Bowen’s disease, progressive thickening or ulceration of a lesion, rapid enlargement, usually painless. In immunocompromised individuals, often multiple lesions with rapid progression.

Histology shows atypical keratinocyte infiltration from the stratum spinosum. Hallmarks: squamous cell atypia, keratin pearls (squamous eddies), dyskeratosis, high mitotic activity, and potential perineural invasion. Immunohistochemistry:

• BerEP4 negative (differentiates from BCC)
• CAM 5.2 to distinguish from adnexal tumors
• p16/HPV testing for mucosal SCC

• Local tissue destruction
• Recurrence
• Lymphatic and hematogenous metastasis
• Perineural invasion
• Pain in advanced cases
• Secondary malignancies
• Higher recurrence in high-risk cases

Early-stage SCC has an excellent prognosis. Risk of metastasis:

• Tumor <2 mm thick: <1%
• 2–6 mm: ~4%
• 6 mm: up to 16%
  Median survival with metastases is approximately 2 years. With prompt treatment, cure rates >95 % are achievable. Higher recurrence risk in lip, ear, and genital locations or in immunosuppressed patients.

• Consistent sun protection (sunscreen, clothing, behavior)
• Avoidance of artificial UV sources
• Routine skin checks in high-risk individuals
• HPV vaccination (for anogenital SCC prevention)
• Patient education on early signs
• Monitoring of immunosuppressed patients

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