Definition/General
Introduction:
Inflammatory changes in sputum cytology represent non-neoplastic reactive changes in respiratory epithelium
They result from various irritants and inflammatory stimuli
Accurate recognition is crucial to avoid misdiagnosis of malignancy
These changes are reversible with removal of inciting factors.
Origin:
Inflammatory changes arise from chronic irritation of respiratory mucosa
Common causes include smoking
Air pollution
Occupational exposures
Chronic infections
Allergic reactions
Chemical irritants
Gastroesophageal reflux.
Classification:
Classified by inflammatory pattern and cellular changes
Acute inflammatory changes
Chronic inflammatory changes
Reactive epithelial changes
Squamous metaplasia
Dysplastic changes
Repair and regeneration.
Epidemiology:
Most common finding in sputum cytology
Higher prevalence in smokers
Urban populations show increased incidence
Occupational exposures contribute significantly
Age-related increase
Gender differences related to smoking patterns.
Clinical Features
Presentation:
Chronic cough (most common symptom)
Sputum production
Shortness of breath
Chest tightness
Wheezing
Recurrent respiratory infections
Voice changes.
Symptoms:
Persistent cough for >3 weeks
Change in sputum characteristics
Dyspnea on exertion
Chest discomfort
Throat irritation
Hoarse voice
Exercise intolerance.
Risk Factors:
Smoking (most important)
Air pollution exposure
Occupational irritants
Chronic respiratory infections
Gastroesophageal reflux
Allergic conditions
Immunocompromised state.
Screening:
Clinical history and examination
Chest imaging
Pulmonary function tests
Sputum cytology
Bronchoscopy if indicated
Environmental assessment.
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Gross Description
Appearance:
Variable sputum appearance
Clear to white (allergic)
Yellow-green (infectious component)
Blood-streaked (severe irritation)
Thick, tenacious
Frothy (chronic changes).
Characteristics:
Mucoid to mucopurulent
Increased viscosity
Variable volume
Seasonal variations
Related to exposures
May contain debris.
Size Location:
Variable daily volume (5-100 mL)
Upper and lower respiratory tract
Diffuse involvement
Bilateral changes
Regional variations based on exposure.
Multifocality:
Generalized inflammatory response
Focal areas of severe change
Progressive involvement
Reversible changes
Chronic vs acute patterns.
Microscopic Description
Histological Features:
Reactive epithelial changes
Nuclear enlargement and pleomorphism
Prominent nucleoli
Increased mitotic activity
Squamous metaplasia
Inflammatory cell infiltrate
Ciliocytophthoria.
Cellular Characteristics:
Enlarged nuclei with smooth contours
Increased nuclear-cytoplasmic ratio
Prominent nucleoli
Abundant cytoplasm
Well-defined cell borders
Ciliated cell changes
Goblet cell hyperplasia.
Architectural Patterns:
Epithelial hyperplasia
Squamous metaplasia
Loss of cilia
Goblet cell proliferation
Basal cell hyperplasia
Reserve cell hyperplasia.
Grading Criteria:
Mild reactive changes: Minimal nuclear atypia
Moderate changes: Nuclear enlargement and pleomorphism
Severe changes: Marked atypia but benign features
Dysplastic changes: Precancerous alterations.
Immunohistochemistry
Positive Markers:
Cytokeratins (CK5/6, CK7, CK20)
p63 (basal cells)
TTF-1 (pneumocytes)
Surfactant proteins
Ki-67 (proliferation)
p53 (may be positive).
Negative Markers:
Malignancy-specific markers
Viral inclusions
Fungal stains
Mycobacterial stains
High-grade dysplasia markers.
Diagnostic Utility:
Helps distinguish reactive from neoplastic changes
Cell type identification
Proliferation assessment
Degree of atypia
Exclude malignancy
Monitor progression.
Molecular Subtypes:
Smoking-related changes
Infection-related changes
Allergic inflammatory changes
Chemical irritant changes
Radiation-induced changes
Drug-induced changes.
Molecular/Genetic
Genetic Mutations:
p53 alterations (in severe dysplasia)
EGFR upregulation
Inflammatory pathway genes
DNA repair gene changes
Cyclooxygenase upregulation
Antioxidant enzyme changes.
Molecular Markers:
Inflammatory cytokines
Growth factors
Oxidative stress markers
DNA damage markers
Repair pathway activation
Telomerase activity.
Prognostic Significance:
Most changes are reversible
Severe dysplasia may progress
Chronic irritation increases cancer risk
Early intervention prevents progression
Monitoring required
Risk stratification needed.
Therapeutic Targets:
Anti-inflammatory agents
Antioxidants
Mucolytics
Bronchodilators
Smoking cessation
Environmental control.
Differential Diagnosis
Similar Entities:
Squamous cell carcinoma (malignant features)
Adenocarcinoma (glandular atypia)
Dysplasia (precancerous changes)
Viral cytopathic effects
Chemical pneumonitis.
Distinguishing Features:
Reactive: Smooth nuclear contours
Reactive: Uniform chromatin
Malignancy: Irregular nuclear contours
Malignancy: Coarse chromatin
Dysplasia: Progressive atypia
Viral: Inclusion bodies.
Diagnostic Challenges:
Distinguishing severe reactive changes from dysplasia
Atypical squamous metaplasia
Radiation effects
Chemotherapy effects
Infectious complications.
Rare Variants:
Radiation pneumonitis
Drug-induced pneumonitis
Hypersensitivity pneumonitis
Organizing pneumonia
Eosinophilic pneumonia.
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, [volume] mL, [appearance], adequate for evaluation
Diagnosis
Inflammatory changes - [mild/moderate/severe] reactive changes
Cellular Changes
Shows [reactive epithelial changes] with [inflammatory pattern]
Microscopic Findings
Reactive changes showing [nuclear enlargement] and [cytoplasmic changes]
Inflammatory Pattern
Inflammatory pattern: [neutrophilic/lymphocytic/eosinophilic/mixed]
Squamous Metaplasia
Squamous metaplasia: [present/absent], [mild/moderate/severe]
Atypia Assessment
Atypia: [reactive/dysplastic], no malignant cells identified
Clinical Correlation
Clinical correlation with [exposures] and [symptoms] recommended
Final Diagnosis
Sputum cytology: Reactive inflammatory changes