Definition/General
Introduction:
Squamous cell carcinoma in sputum cytology represents malignant transformation of bronchial epithelium
It is the second most common lung cancer type (25-30%)
Strongly associated with tobacco smoking
Central location makes it detectable by sputum cytology.
Origin:
Originates from bronchial epithelium undergoing squamous metaplasia
Sequential progression from metaplasia to dysplasia to carcinoma
Central airways most commonly affected
Chronic irritation and smoking are major factors
p53 mutations are frequent.
Classification:
Classified by degree of differentiation
Well-differentiated: Clear keratinization and intercellular bridges
Moderately differentiated: Some keratinization present
Poorly differentiated: Minimal keratinization
Keratinizing vs non-keratinizing variants.
Epidemiology:
Strong male predominance (4:1 ratio)
Peak incidence 60-70 years
90% associated with smoking
Higher rates in developing countries
Declining incidence in developed countries
Strong correlation with pack-years of smoking
Higher rates in industrial areas.
Clinical Features
Presentation:
Persistent cough (most common symptom)
Hemoptysis (blood-streaked sputum)
Dyspnea and chest pain
Weight loss and anorexia
Hoarse voice (recurrent laryngeal nerve involvement)
Superior vena cava syndrome
Pneumonia or atelectasis.
Symptoms:
Chronic cough with change in character
Hemoptysis (30-50% of patients)
Chest pain (pleuritic or dull)
Shortness of breath
Fatigue and weakness
Fever (post-obstructive pneumonia)
Wheezing or stridor.
Risk Factors:
Tobacco smoking (most important - 85% of cases)
Passive smoking
Occupational exposures (asbestos, radon)
Air pollution
Chronic lung disease (COPD, pulmonary fibrosis)
Family history of lung cancer
Previous radiation therapy.
Screening:
Low-dose CT screening (high-risk patients)
Sputum cytology (limited sensitivity)
Chest X-ray (often normal early)
Bronchoscopy with biopsy
Smoking cessation counseling
Annual screening in high-risk groups.
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Gross Description
Appearance:
Purulent sputum with thick consistency
Blood-streaked or frankly bloody
Yellow-green or rust-colored
Mucoid to mucopurulent
Foul odor may be present
Increased volume production.
Characteristics:
Thick, viscous consistency
Opaque appearance
May contain necrotic tissue
Inflammatory debris abundant
Poor quality specimens common
Bacterial contamination frequent.
Microscopic Description
Immunohistochemistry
Positive Markers:
p63 (nuclear, strong and diffuse)
CK5/6 (cytoplasmic)
CK14 and CK17
p40 (more specific than p63)
Desmoglein-3
CK34βE12
Involucrin (in keratinizing areas).
Negative Markers:
TTF-1 (negative - distinguishes from adenocarcinoma)
Napsin A (negative)
CK7 (usually negative)
CK20 (negative)
CDX2 (negative)
Chromogranin and synaptophysin (negative).
Diagnostic Utility:
p40 most specific squamous marker
p63 sensitive but less specific
TTF-1 negativity excludes adenocarcinoma
CK5/6 supports squamous differentiation
Combination panel recommended
Helps subtyping of non-small cell lung cancer.
Molecular/Genetic
Differential Diagnosis
Similar Entities:
Adenocarcinoma with squamous features
Adenosquamous carcinoma
Large cell carcinoma
Metastatic squamous carcinoma
Severe squamous dysplasia
Reactive squamous metaplasia.
Distinguishing Features:
Squamous carcinoma: p63+, TTF-1-, keratinization
Adenocarcinoma: TTF-1+, p63-, glandular features
Large cell: No differentiation markers
Metastatic: Clinical correlation, site-specific markers
Dysplasia: Less severe atypia
Reactive: Inflammation, clinical correlation.
Diagnostic Challenges:
Poorly differentiated squamous carcinoma difficult
Distinguishing from large cell carcinoma
Adenosquamous carcinoma components
Metastatic disease consideration
Small cell carcinoma with squamous features
Reactive atypia in smokers.
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
Sputum specimen, [collection method], [volume] ml
Specimen Adequacy
[adequate/inadequate] - [criteria met/not met]
Cellular Findings
Malignant cells identified with [specific features]
Squamous Features
[keratinization present/absent], [other squamous characteristics]
Nuclear Features
[nuclear characteristics described]
Background
[inflammatory/necrotic/hemorrhagic] background
Diagnosis
Malignant cells consistent with squamous cell carcinoma
Differential Diagnosis
Consider [relevant differentials based on morphology]
Recommendations
Bronchoscopy with tissue biopsy for confirmation and subtyping