What are the potential causes of a left-sided massive pleural effusion?

Causes of Left-Sided Massive Pleural Effusion

Malignancy is the most common cause of massive pleural effusion, with lung cancer, breast cancer, lymphoma, and mesothelioma being the primary culprits, though left-sided location should raise suspicion for non-hepatic causes since hepatic hydrothorax is predominantly right-sided. 1

Primary Malignant Causes

The following malignancies account for the majority of massive pleural effusions:

• Lung cancer is the leading malignant cause, accounting for 25-52% of all malignant pleural effusions and approximately one-third of all malignant effusions. 1, 2
• Breast cancer represents 3-27% of malignant effusions on cytology, with 36-65% of patients with disseminated breast cancer developing pleural effusions. 1
• Lymphoma accounts for approximately 10-22% of malignant pleural effusions and characteristically presents with lymphocyte-predominant exudates. 1, 2
• Mesothelioma characteristically presents with massive effusion and dull, aching chest pain rather than pleuritic pain, often showing absence of contralateral mediastinal shift despite large effusion volume due to extensive pleural involvement. 1

Critical Diagnostic Distinction: Left vs. Right Laterality

Left-sided massive effusion should prompt consideration of causes other than hepatic hydrothorax, which occurs in only 17% of cases on the left side compared to 73% on the right side. 3

• Hepatic hydrothorax in cirrhosis is typically right-sided (73%), with left-sided presentation occurring in only 17% of cases and bilateral in 10%. 3
• A left-sided effusion in the setting of cirrhosis should raise suspicion for alternative diagnoses including infection, pancreatitis, malignancy, or cardiopulmonary causes, particularly if the serum to pleural fluid albumin gradient is ≤1.1 g/dL or if ascites is absent. 3

Other Important Causes

Beyond malignancy, consider these etiologies:

• Tuberculosis is the most common infectious cause of exudative lymphocytic effusions and should be reconsidered in persistent undiagnosed effusions. 2
• Parapneumonic effusion/empyema from pneumonia, though these typically present with fever and acute illness rather than massive accumulation. 3
• Pulmonary embolism should be suspected when dyspnea is out of proportion to effusion size, with approximately 75% of patients having pleuritic pain history. 3
• Continuous ambulatory peritoneal dialysis (CAPD) can rarely cause massive left-sided pleural effusion even with proper catheter position. 4
• Systemic lupus erythematosus affects up to 50% of patients during disease course and produces lymphocytic exudates. 2

Key Diagnostic Features in Massive Effusions

When encountering a massive left-sided pleural effusion, look for these critical findings:

• Absence of mediastinal shift implies one of three diagnoses: mediastinal fixation by tumor, mainstem bronchus occlusion, or extensive pleural involvement. 1
• History of asbestos exposure identified on CT (pleural plaques) should raise suspicion for mesothelioma. 1
• Hemoptysis with pleural effusion is highly suggestive of bronchogenic carcinoma. 1, 5

Immediate Diagnostic Approach

Perform diagnostic thoracentesis on any unilateral effusion, sending pleural fluid for nucleated cell count with differential, total protein, LDH, glucose, pH, and cytology. 1

• Apply Light's criteria first to distinguish transudate from exudate (sensitivity 98%, specificity 72%). 2
• Calculate serum to pleural fluid albumin gradient; >1.1 g/dL suggests transudate (such as hepatic hydrothorax), while ≤1.1 g/dL suggests exudate. 3
• Cytology has variable sensitivity (40-87% depending on tumor type), so negative cytology does not exclude malignancy. 1
• If malignancy remains suspected after negative initial cytology, thoracoscopy should be considered, which has superior diagnostic yield (85% sensitivity for lymphoma with chromosome analysis). 2

Common Clinical Pitfalls

• Do not assume bilateral effusions exclude malignancy—malignant effusions can be bilateral. 1, 5
• Do not perform aspiration for bilateral effusions in a clinical setting strongly suggestive of transudate (such as heart failure with normal-sized heart) unless there are atypical features or failure to respond to therapy. 3
• Do not overlook drug-induced effusions—tyrosine kinase inhibitors are now the most common drugs causing exudative pleural effusions. 2
• Always obtain detailed occupational history including asbestos exposure when investigating all pleural effusions. 2

Management Considerations

• Therapeutic thoracentesis should be performed in virtually all dyspneic patients with massive effusions to determine effect on breathlessness and rate of recurrence. 1
• Failure of complete lung expansion after drainage indicates either endobronchial obstruction or trapped lung. 1
• Before attempting pleurodesis, complete lung expansion must be demonstrated; initial pleural fluid pressure less than 10 cm H₂O at thoracentesis makes trapped lung likely. 1