What is squamous cell carcinoma?

Squamous Cell Carcinoma: Definition, Types, and Clinical Implications

Squamous cell carcinoma (SCC) is a malignant tumor that arises from keratinizing cells of the epithelium, is locally invasive, and has the potential to metastasize to other organs of the body. 1

Definition and Origin

Squamous cell carcinoma develops from epithelial cells in various body locations:

• Cutaneous SCC: Originates from the keratinizing cells of the epidermis or its appendages 1
• Mucosal SCC: Develops in the oral cavity, pharynx, and larynx 1
• Cervical SCC: Accounts for 70-80% of cervical cancers 1

Epidemiology

• Second most common skin cancer after basal cell carcinoma 1
• Represents approximately 20% of all non-melanoma skin cancers 2
• Incidence is rising in many countries 1
• Diagnosed at a rate of 15-35 per 100,000 people with an annual increase of 2-4% 2
• More common in men, people over 75 years of age, and inhabitants of southern and mid-western USA 2

Risk Factors

Primary Risk Factors:

• Ultraviolet light exposure: Chronic sun exposure is the most common cause of cutaneous SCC 1
• Tobacco use and alcohol consumption: Account for 75-85% of head and neck SCC 1
• Human papillomavirus (HPV) infection: Particularly important in oropharyngeal and cervical SCC 1

Secondary Risk Factors:

• Previous exposure to ionizing radiation or arsenic 1
• Chronic wounds, scars, burns, ulcers, or sinus tracts 1
• Pre-existing lesions such as Bowen's disease (intraepidermal SCC) 1
• Immunosuppression (transplant recipients, lymphoma/leukemia patients) 1, 2
• Chronic inflammatory processes 1
• Genetic conditions (Fanconi anemia, xeroderma pigmentosum, etc.) 1

Clinical Presentation

SCC typically presents as:

• An indurated nodular keratinizing or crusted tumor 1
• May ulcerate or present as an ulcer without keratinization 1
• Can be exophytic (growing outward) or endophytic (with stromal infiltration) 1
• May cause symptoms including pain, bleeding, and functional impairment 1

Histopathological Classification

Cutaneous SCC Subtypes:

• Keratinizing type: Characterized by keratin pearls 1
• Non-keratinizing type: May show individual cell keratinization but no keratin pearls 1
• Adenoid (acantholytic) SCC: Higher risk of recurrence 1
• Adenosquamous (mucin-producing) SCC: Higher risk of recurrence 1
• Verrucous carcinoma: Generally less aggressive 1
• Basosquamous carcinoma: Shows features of both basal and squamous cell carcinoma 1

Grading:

• Based on degree of differentiation (well, moderately, or poorly differentiated) 1
• Broders' grading system is commonly used but does not always correlate reliably with prognosis 1

High-Risk Features

Features associated with higher risk of recurrence or metastasis:

• Tumor diameter greater than 2 cm 1
• Depth of invasion greater than 2-4 mm 1, 2
• Poor histological differentiation 2
• High-risk anatomic locations (face, ears, genitalia, hands, feet) 2
• Perineural involvement 1, 2
• Lymphovascular invasion 1
• Recurrent disease 2
• Immunosuppression 2
• Rapid growth 1
• Neurologic symptoms (pain, paresthesia, motor deficits) 1

Diagnosis

Diagnosis is established histologically through biopsy. A comprehensive histology report should include:

• Pathological pattern and cell morphology
• Degree of differentiation
• Histological grade
• Depth and level of invasion
• Presence or absence of perineural, vascular, or lymphatic invasion
• Status of excision margins 1

Prognosis

Prognosis varies significantly based on location, stage, and risk factors:

• Five-year survival rates range from 25% (hypopharyngeal SCC) to 61% (laryngeal SCC) 1
• Metastatic cutaneous SCC has a mortality rate exceeding 70% 2
• HPV-positive oropharyngeal SCC has a significantly better outcome than HPV-negative disease 1

Management Considerations

Treatment options depend on tumor characteristics, location, and patient factors:

• Surgery: Primary treatment for most SCCs, including Mohs micrographic surgery for high-risk areas 3
• Radiation therapy: Can be used as primary treatment in certain locations or as adjuvant therapy 2
• Systemic therapy: For metastatic or locally advanced disease 2
• Combination approaches: Often needed for high-risk or metastatic disease 2

Prevention

• Sun protection (avoidance, protective clothing, sunscreens) 1
• HPV vaccination 1
• Regular skin examinations, especially for high-risk individuals 1
• Smoking cessation and alcohol moderation 1

Understanding the specific type, location, and risk factors of SCC is crucial for determining appropriate treatment and follow-up to minimize morbidity and mortality.