3.3.4 Squamous Cell Carcinoma

Epidermoid carcinoma, keratinocyte tumor

The incidence is about 30-50 /100,000 per year in Europe. Incidence is 387/100,000/year in Australia.

Squamous cell carcinoma is a malignant keratinocytic tumour that starts in the epidermis and potentially can invade into deeper layers and metastatize.

Squamous cell carcinoma arises on previously damaged skin: UV (which causes mutations in the p53 tumour suppressor gene; especially UVB), ionizing radiation, arsenic, tar, soot, scars, HPV (β-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38). Lesions tend to arise from precursors lesions: actinic keratoses, scars, chronic ulcers. Predisposing factors are skin types I and II, occupations with marked UV exposure (farmers, mountaineers, sailors, roofers and construction workers).

Lesions are hyperkeratotic, irregular papules or nodules, sometimes crusted and ulcerated, more commonly occurring on sun-exposed areas.

According to dermatopathologic findings, the grading is related to differention of tumor cells with final complete de-differentiation (Broder’s classification).

Histologically, they can be classified as well differentiated, moderately, poorly differentiated or anaplastic cutaneous SCC.

Cutaneous SCC can be classified as low-risk or high-risk, depending on the chance of tumour recurrence and metastasis. High-risk SCC have diameter greater than or equal to 2 cm, located in high-risk area, arising in immune suppressed patient, have a histological thickness greater than 2 mm, poor differentiated histology, or with the invasion of the subcutaneous tissue, nerves and blood vessels.

Dermoscopy can aid in diagnosing, classification, and follow-up; high frequency ultrasound and optical coherence tomography allow to determine depth, length and shape of tumor; reflectance confocal microcopy is used for diagnosis.

Histology shows hyperkeratosis, strands of epithelium extending into dermis, atypia, mitoses, inflammatory infiltrate, dyskeratosis, single cell necrosis (apoptosis with eosinophilic cytoplasm), and keratin pearls. Degree of differentiation varies from grade I (well-differentiated, risk of metastasis 1-2%), to grade IV (poorly differentiated with high risk).

Tumours on tongue, vulva, penis and anus have greater risk of metastasis. Prognosis is worse in immunosuppressed patients.

Local tissue destruction and metastasis are the main complications.

Squamous cell carcinoma must be differentiated from actinic keratoses, Bowen’s disease, basal cell carcinoma, keratoacanthoma, verruca vulgaris, hypertrophic lichen planus and tumors of skin adnexal structures.

Treatment depends on size and localization. Surgical excision should be done with histologically proven margins: other options are cryosurgery, radiotherapy, radiofrequency therapy with bleomycin, immune modulators (check point inhibitors) and specific targeted therapies.