Definition/General
Introduction:
Squamous cell carcinoma is a major subtype of non-small cell lung cancer
Represents 25-30% of all lung cancers
Shows keratinization and intercellular bridges
Strong smoking association.
Origin:
Arises from bronchial epithelium
Develops through squamous metaplasia-dysplasia-carcinoma sequence
Central location typical
Associated with tobacco exposure.
Classification:
WHO 2021: Squamous cell carcinoma
Keratinizing type
Non-keratinizing type
Basaloid variant
Part of NSCLC family.
Epidemiology:
Peak incidence 6th-8th decades
Male predominance (3:1)
Strong smoking association
Central location more common
Decreasing incidence with smoking reduction.
Clinical Features
Presentation:
Cough (80%)
Hemoptysis (50%)
Dyspnea
Chest pain
Weight loss
Central airway obstruction
Paraneoplastic syndromes.
Symptoms:
Productive cough
Blood-streaked sputum
Shortness of breath
Chest discomfort
Hoarseness (recurrent laryngeal nerve)
Superior vena cava syndrome.
Risk Factors:
Tobacco smoking (85% cases)
Environmental tobacco smoke
Occupational exposures (asbestos, radon)
Air pollution
Genetic susceptibility
Prior lung disease.
Screening:
Low-dose CT screening (high-risk patients)
Chest X-ray
Sputum cytology
Bronchoscopy
Smoking cessation counseling.
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Gross Description
Appearance:
Gray-white, firm mass
Central location (hilar/perihilar)
Cavitation common
Necrosis and hemorrhage
Obstructs bronchi
Irregular margins.
Characteristics:
Firm consistency
Tan-gray color
Central necrosis
Cavitary lesions
Infiltrative growth
Hilar lymph node enlargement.
Size Location:
Central/hilar location (70%)
Upper lobe predilection
Endobronchial growth
Variable size (2-15 cm)
Mediastinal extension
Chest wall invasion.
Multifocality:
Usually solitary
Synchronous tumors (5%)
Metachronous tumors (field cancerization)
Multifocal squamous dysplasia
Second primary cancers.
Microscopic Description
Histological Features:
Squamous differentiation
Keratinization (individual cell or pearl formation)
Intercellular bridges
Stratified epithelial pattern
Desmoplastic stroma
Invasive growth.
Cellular Characteristics:
Polygonal cells
Eosinophilic cytoplasm
Distinct cell borders
Nuclear pleomorphism
Prominent nucleoli
Mitotic activity variable.
Architectural Patterns:
Nests and sheets
Keratinizing pearls
Individual cell keratinization
Invasive islands
Desmoplastic reaction
Surface ulceration.
Grading Criteria:
Well-differentiated: Extensive keratinization, minimal atypia
Moderately differentiated: Moderate keratinization, moderate atypia
Poorly differentiated: Minimal keratinization, marked atypia
Grade affects prognosis.
Immunohistochemistry
Positive Markers:
p63 - positive (nuclear)
CK5/6 - positive
p40 - positive (specific)
34βE12 - positive
CK14 - positive
Desmoglein-3 - positive.
Negative Markers:
TTF1 - negative (vs adenocarcinoma)
Napsin A - negative
CK7 - variable/negative
CK20 - negative
CDX2 - negative.
Diagnostic Utility:
p40 most specific for squamous differentiation
p63 sensitive but less specific
TTF1 negative helps exclude adenocarcinoma
CK5/6 supports squamous lineage
Combination panel recommended.
Molecular Subtypes:
All SCC: p40+, p63+, TTF1-
Keratinizing type: Strong squamous markers
Non-keratinizing: Same markers, less keratin
Basaloid variant: p63+ with basaloid features.
Molecular/Genetic
Genetic Mutations:
TP53 mutations (80-90%)
PIK3CA mutations (20%)
CDKN2A deletions
SOX2 amplification
FGFR1 amplification
DDR2 mutations.
Molecular Markers:
p53 pathway disruption
PI3K/AKT pathway activation
Cell cycle dysregulation
DNA repair defects
Chromosomal instability
High mutational burden.
Prognostic Significance:
Stage most important
Performance status
Grade influences outcome
Cavitation may predict response
p16 loss: Poor prognosis
PIK3CA mutations: Better response to PI3K inhibitors.
Therapeutic Targets:
Surgery (early stage)
Platinum-based chemotherapy
Radiation therapy
Immunotherapy (anti-PD-1/PD-L1)
FGFR inhibitors
PI3K inhibitors.
Differential Diagnosis
Similar Entities:
Adenocarcinoma with squamous features
Adenosquamous carcinoma
Large cell carcinoma
Metastatic squamous carcinoma
Poorly differentiated carcinoma
Sarcomatoid carcinoma.
Distinguishing Features:
Squamous carcinoma: p40+, TTF1-, keratinization
Adenocarcinoma: TTF1+, Napsin A+
Adenosquamous: Both components present
Large cell: No specific differentiation
Metastatic: Clinical correlation, organ-specific markers.
Diagnostic Challenges:
Poorly differentiated squamous carcinoma
Adenosquamous carcinoma
Basaloid variant
Metastatic vs primary
Small biopsy specimens.
Rare Variants:
Basaloid squamous carcinoma
Spindle cell (sarcomatoid) variant
Clear cell variant
Small cell variant.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[Lobectomy/pneumonectomy/wedge resection] specimen with tumor
Tumor Description
Squamous cell carcinoma measuring [X] cm in [location] with [cavitation present/absent]
Microscopic Features
Invasive squamous cell carcinoma with keratinization, intercellular bridges, and [grade] differentiation
Differentiation Grade
[Well/moderately/poorly] differentiated squamous cell carcinoma
pT Stage
pT[stage] - [staging details]
Lymphovascular Invasion
Lymphovascular invasion: [present/absent]
Margins
Surgical margins: [negative/positive], closest margin [X] mm
Lymph Nodes
[X] of [Y] lymph nodes positive for carcinoma
Immunohistochemistry
p40: Positive, p63: Positive, TTF1: Negative, Napsin A: Negative
Final Diagnosis
Squamous cell carcinoma, [grade], pT[stage]N[stage]M[stage]