Can Empyema Mimic Mesothelioma?
Yes, empyema and other benign pleural diseases can mimic malignant pleural mesothelioma (MPM) in clinical presentation, making differentiation challenging and requiring histological confirmation for definitive diagnosis.
Clinical and Radiographic Overlap
Empyema and MPM share several overlapping features that create diagnostic confusion:
Common Presenting Features
- Both conditions present with pleural effusion (seen in 74-76% of MPM cases), chest pain, and dyspnea 1, 2
- Pleural thickening occurs in both conditions—seen in 88-94% of MPM cases but also characteristic of organizing pleuritis and empyema 3
- Unilateral pleural involvement is typical for both empyema and MPM (bilateral disease occurs in only 3% of MPM) 3
Radiographic Similarities
- CT imaging shows pleural thickening in both conditions, though nodular pleural thickening (sensitivity 37-48%, specificity 86-97%) and pleural thickening >1 cm (sensitivity 35-47%, specificity 64-94%) favor malignancy 3
- Both can demonstrate loculated effusions and pleural enhancement on contrast-enhanced imaging 3
Critical Distinguishing Features
Histopathological Differentiation
The key distinction lies in histological invasion patterns that cannot be determined by imaging or cytology alone:
- Empyema/reactive pleuritis shows a layered or zonal pattern of mesothelial proliferation with fibrin and granulation tissue, with elongated capillaries perpendicular to the pleural surface 1
- MPM demonstrates haphazard irregular infiltration into thickened pleura with deep penetration of chest wall fat, indicating true stromal invasion 1
- Reactive mesothelial proliferations in empyema can show significant cytological atypia and are impossible to distinguish from MPM on cytology alone 1
Diagnostic Pitfalls
- The "fake fat phenomenon" in organizing pleuritis creates artificial fat-like spaces between mesothelial cells that can be mistaken for invasion on small biopsies 1
- Cytology of pleural fluid has low sensitivity (30-75%) and cannot distinguish benign reactive mesothelial proliferation from malignancy because subpleural fat tissue invasion cannot be assessed 1
- Mesothelial hyperplasia associated with chronic empyema may mimic mesothelioma in clinical aspects 4
Diagnostic Algorithm
Step 1: Initial Evaluation
- Obtain detailed occupational history for asbestos exposure (latency period typically decades) 1, 5
- Perform contrast-enhanced CT chest to assess pleural thickening pattern, mediastinal involvement, and presence of pleural plaques 3
Step 2: Fluid Analysis
- Thoracentesis with cytology can suggest mesothelial origin but is insufficient for definitive diagnosis 1
- CEA levels are NOT elevated in MPM (negative marker) but are elevated in adenocarcinoma—useful for ruling out MPM if cytology is inconclusive 1
- Mesothelin levels lack specificity and should not be used as specific markers 1
Step 3: Tissue Diagnosis (Mandatory)
- Thoracoscopy (VATS or pleuroscopy) is the recommended diagnostic method to obtain adequate histology, optimally stage, and allow fluid evacuation 1
- Biopsy both abnormal AND normal-appearing tissue, as MPM can be difficult to identify 1
- When thoracoscopy is contraindicated, ultrasound-guided core biopsies are the alternative 1
- Blind biopsies are NOT recommended due to complication risk and low yield 1
Step 4: Ancillary Testing on Tissue
- Immunohistochemistry is pivotal: Calretinin, WT1, D2-40 (podoplanin), and cytokeratin 5/6 support MPM diagnosis 1
- p16INK4a/p14ARF homozygous deletion at chromosome 9p21 by FISH shows promising results for early MPM detection 1
- Cytokeratin staining highlights disorderly arrangement of invasive cells (MPM) versus horizontal array (reactive) 1
Key Clinical Caveat
The diagnosis of MPM requires histological evidence of true stromal or parenchymal invasion—this cannot be established by imaging, clinical presentation, or cytology alone 1. The term "atypical mesothelial proliferation" should be used when cytology shows atypia but invasion cannot be confirmed, leaving the possibility of MPM open without confirming it 1.