Malignant tumour that arises from supra-basal keratinocytes
Aetiology
Major Risk Factors
Factor | Role |
Chronic UV exposure (UVB) | DNA damage (p53 mutation) |
Actinic keratosis | Precancerous lesion |
Immunosuppression | Aggressive behavior |
Chronic wounds/scars | Marjolin ulcer |
Ionizing radiation | Carcinogenesis |
HPV infection | Anogenital & periungual SCC |
Chemical carcinogens | Arsenic, tar |
Pathophysiology
- UV radiation → DNA damage in keratinocytes
- Mutation of tumor suppressor genes (p53, NOTCH)
- Progression:
- Normal skin → Actinic keratosis → SCC in situ → invasive SCC
- Failure of immune surveillance enhances tumor progression
Growth and spread
- Locally invasive
- Low but definite risk of metastases
- Poor prognosis once metastatic
Clinical presentation
Typical Lesions
- Firm, hyperkeratotic papule, plaque, or nodule
- May ulcerate → crateriform or ulcerative lesion
- Often erythematous with scale or crust
- Lesions may be tender or painful

Common Sites
- Sun-exposed areas
- Face
- Scalp (balding)
- Ears
- Dorsum of hands
- Lips (lower lip)
- Anogenital region (HPV-related)
Investigations
Histopathology (Gold standard)
- Invasive cords and nests of atypical squamous cells
- Keratin pearly horn formation (well-differentiated SCC)
- Cellular atypia and mitoses

Grading
Grade | Features |
Well-differentiated | Prominent keratinization |
Moderately differentiated | Less keratinization |
Poorly differentiated | Minimal keratinization, aggressive |
Management
- Usually complete surgical excision (+ biopsy) with a wide margin
- May be treated topically if smaller and not invasive