Definition/General

Introduction:
-Pleural empyema is purulent infection of the pleural space
-It contains frank pus with high bacterial load
-Characterized by thick, viscous fluid with neutrophilic predominance
-Represents complicated parapneumonic effusion
-Requires urgent drainage and antibiotic therapy.
Origin:
-Results from bacterial invasion of pleural space
-Most commonly from pneumonia extension (60% cases)
-Post-surgical complications (thoracic surgery)
-Chest trauma with secondary infection
-Hematogenous spread from distant infection sites.
Classification:
-Classified as complicated parapneumonic effusion
-Stage 1: Simple parapneumonic (sterile)
-Stage 2: Complicated parapneumonic (fibrinopurulent)
-Stage 3: Frank empyema (organizing stage)
-Based on Light criteria for empyema.
Epidemiology:
-Incidence 2-10 per 100,000 population annually
-Male predominance (2:1 ratio)
-Bimodal age distribution: children <5 years and adults >65 years
-Mortality 5-15% with treatment
-Higher prevalence in immunocompromised patients.

Clinical Features

Presentation:
-High-grade fever with chills and rigors
-Severe chest pain (sharp, stabbing)
-Marked dyspnea and tachypnea
-Productive cough with purulent sputum
-Night sweats and malaise
-Sepsis syndrome may develop.
Symptoms:
-Fever >38.5°C (90% cases)
-Severe pleuritic chest pain (85% cases)
-Dyspnea and tachypnea (80% cases)
-Productive cough (70% cases)
-Night sweats (60% cases)
-Weight loss and anorexia (50% cases)
-Fatigue and weakness.
Risk Factors:
-Pneumonia (most common predisposing factor)
-Immunocompromised state
-Diabetes mellitus
-Chronic lung disease
-Alcohol abuse
-Post-thoracic surgery
-Chest trauma
-Intravenous drug use.
Screening:
-Chest X-ray shows pleural opacity
-CT thorax for loculation assessment
-Ultrasound-guided thoracentesis
-Blood cultures (positive in 20-30%)
-Procalcitonin and inflammatory markers elevated.

Master Pleural Empyema Pathology with RxDx

Access 100+ pathology videos and expert guidance with the RxDx app

Gross Description

Appearance:
-Pleural fluid is thick, viscous, and purulent
-Yellow-green to gray-brown color
-Foul odor may be present (anaerobic bacteria)
-Opaque and turbid appearance
-May contain fibrin clots and debris.
Characteristics:
-pH <7.30 (usually <7.20)
-Glucose <60 mg/dL (often <30 mg/dL)
-LDH >1000 U/L
-Protein >3 g/dL
-Low complement levels
-Gram stain positive in 60-80% cases.
Size Location:
-Usually unilateral (90% cases)
-Right-sided slightly more common
-Loculated due to fibrin deposition
-Multi-loculated in advanced cases
-May form pleural peel in chronic cases.
Multifocality:
-Typically unilateral involvement
-Multiple loculations common
-Pleural thickening and adhesions
-Trapped lung in chronic cases
-Bronchopleural fistula may develop (5-10% cases).

Microscopic Description

Histological Features:
-Pleural fluid shows massive neutrophilic infiltration (>75% neutrophils)
-Very high cell count (>50,000 cells/μL)
-Degenerative neutrophils with nuclear fragmentation
-Abundant cellular debris
-Bacteria visible on gram stain.
Cellular Characteristics:
-Mature neutrophils with multi-lobed nuclei
-Degenerative changes: pyknosis, karyorrhexis
-Toxic granulation in neutrophils
-Reactive mesothelial cells (if viable)
-Macrophages with phagocytosed debris.
Architectural Patterns:
-Sheets of neutrophils
-Inflammatory cell aggregates
-Fibrin strands and clots
-Necrotic background with debris
-Bacterial colonies (when visible)
-Reactive mesothelial proliferation (minimal).
Grading Criteria:
-Empyema criteria: Gross pus
-pH <7.30
-Glucose <60 mg/dL
-LDH >1000 U/L
-Positive gram stain/culture
-Neutrophil count >75% of total cells.

Immunohistochemistry

Positive Markers:
-Myeloperoxidase (MPO) positive in neutrophils
-CD15 positive in neutrophils
-Lysozyme positive in macrophages
-CD68 positive in macrophages
-Calretinin in reactive mesothelial cells (if present).
Negative Markers:
-Cytokeratins (except mesothelial cells)
-CEA, TTF-1 to exclude adenocarcinoma
-CD20, CD3 (lymphoid markers)
-S-100 to exclude melanoma
-PSA to exclude prostate metastases.
Diagnostic Utility:
-IHC rarely needed for empyema diagnosis
-Morphology and gram stain usually diagnostic
-May help distinguish from necrotizing malignancy
-Neutrophil markers confirm inflammatory nature
-Bacterial culture most important for diagnosis.
Molecular Subtypes:
-No molecular subtypes
-Bacterial species identification by culture/PCR
-Antibiotic resistance patterns
-16S rRNA sequencing for difficult organisms
-MALDI-TOF for rapid bacterial identification.

Molecular/Genetic

Genetic Mutations:
-No genetic mutations in host cells
-Bacterial DNA detection by PCR
-Resistance genes in bacteria (MRSA, ESBL)
-Virulence factors in pathogenic bacteria
-16S rRNA gene for bacterial identification.
Molecular Markers:
-Procalcitonin markedly elevated
-C-reactive protein >200 mg/L
-Interleukin-6, TNF-alpha elevated
-Lactate levels increased in pleural fluid
-Complement levels decreased.
Prognostic Significance:
-Early drainage improves prognosis
-Multi-drug resistant organisms worsen outcomes
-Delayed treatment leads to organizing empyema
-Comorbidities affect prognosis
-Complete drainage prevents recurrence.
Therapeutic Targets:
-Broad-spectrum antibiotics initially
-Culture-guided therapy after sensitivity
-Pleural drainage: chest tube/VATS
-Fibrinolytic therapy (streptokinase, urokinase)
-Decortication in organizing empyema.

Differential Diagnosis

Similar Entities:
-Complicated parapneumonic effusion (pre-empyema)
-Necrotizing pneumonia with pleural extension
-Malignant pleural effusion with secondary infection
-Fungal empyema (immunocompromised)
-Tuberculous empyema (rare).
Distinguishing Features:
-Empyema: Frank pus
-Empyema: pH <7.30
-Empyema: Very high neutrophil count
-Parapneumonic: Turbid but not purulent
-Malignant: Cytological atypia
-Fungal: Fungal elements on stain.
Diagnostic Challenges:
-Distinguishing from complicated parapneumonic effusion
-Secondary infection in malignant effusion
-Anaerobic empyema may be culture-negative
-Antibiotic-treated empyema may show fewer bacteria
-Need for rapid diagnosis and treatment.
Rare Variants:
-Anaerobic empyema (foul-smelling)
-Fungal empyema (immunocompromised)
-Tuberculous empyema (chronic cases)
-Post-operative empyema
-Empyema necessitans (chest wall extension).

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

Pleural fluid, volume [X] mL, thick, purulent, yellow-green color

Adequacy

Adequate for cytological and microbiological evaluation

Cellularity

Very high cellularity with [X] cells/μL (>50,000 cells/μL)

Cell Differential

Neutrophils: [X]% (>75%), Macrophages: [X]%, Lymphocytes: [X]%, Mesothelial cells: [X]%

Morphological Features

Massive neutrophilic infiltration with degenerative changes. Abundant cellular debris and fibrin. Background shows purulent inflammation.

Gram Stain

Gram stain: [Positive/Negative for bacteria] - [Gram positive/negative cocci/rods]

Biochemical Analysis

pH: [X] (<7.30), Glucose: [X] mg/dL (<60), LDH: [X] U/L (>1000)

Culture Results

Bacterial culture: [Organism identified/Pending/No growth] - Sensitivity: [Pattern]

Final Diagnosis

Pleural empyema - Urgent drainage recommended

Comment

URGENT: Findings consistent with pleural empyema. Immediate chest tube drainage and antibiotic therapy recommended. Clinical team notified.