Answers

Short answers

1 Analysis of the pleural fluid suggests that it is an exudate (pleural fluid protein to total serum protein ratio >0.5). Possible causes include a malignant primary lung tumour with pleural involvement, metastatic malignant pleural effusion, parapneumonic effusion, mesothelioma, tuberculosis, pulmonary embolism, connective tissue disease (such as rheumatoid arthritis), benign asbestos related effusion, pancreatitis, oesophageal rupture, and subphrenic abscess.

2 Computed tomography of the chest and abdomen, and pleural biopsy.

3 Pleural effusion caused by primary lung cancer, mesothelioma, or metastatic disease from another primary source are the most likely causes in this patient. The weight loss, diffuse chest pain, and possible occupational exposure to asbestos (he was a retired joiner) point towards mesothelioma.

Long answers
1. Causes of a unilateral pleural effusion
Unilateral pleural effusion has a wide range of causes (box).¹ Pleural aspiration is vital when investigating any pleural effusion, and samples should be sent for biochemistry (to measure protein, glucose, lactate dehydrogenase (LDH), and pH), microbiology (for a differential cell count, Gram stain, culture, and acid and alcohol fast stain), and cytology. The first step in the analysis of pleural fluid is to determine whether the effusion is a transudate or exudate. Most transudative effusions are caused by an imbalance of hydrostatic-oncotic pressures, whereas exudative pleural effusions are usually caused by pleural inflammation and plasma extravasation as a result of vascular hyperpermeability. Pleural effusions caused by pulmonary embolism and hypothyroidism can be either a transudate or exudate.

According to Light’s criteria,² if at least one of the following is present, the fluid is an exudate:

• Pleural fluid protein to serum protein ratio >0.5
  
• Pleural fluid LDH to serum LDH ratio >0.6
  
• Pleural fluid LDH more than two thirds of the upper limits of the laboratory’s normal value for serum LDH.
  

Although the differential diagnosis of exudative pleural effusion is wide, malignancy is one of the most common causes.³

2. Further investigations
Computed tomography is useful to assess the size of the pleural effusion; the presence of loculation; abnormalities of the underlying lung, abdomen, or pelvis; pleural thickening or nodularity, and mediastinal lymphadenopathy. A pleural biopsy should be considered in patients with an undiagnosed exudative pleural effusion with non-diagnostic cytology. Thoracoscopic pleural biopsy (medical or surgical) has a diagnostic yield of more than 95% for malignancy and should be performed if possible.¹ Computed tomography guided pleural biopsy is useful (sensitivity of 87% for malignancy) if pleural thickening, nodularity, or a mass is seen on contrast enhanced computed tomography.⁴ Blind punch biopsy with an Abrams needle is quick and cheap to perform but has a lower diagnostic yield (ranging from 40% to 75% in different series).⁵ Contraindications to pleural biopsy include a bleeding diathesis, anticoagulation, and infection of the chest wall.

3. Differential diagnoses
Lung cancer (non-small cell and small cell) and breast cancer are the most common tumours that metastasise to the pleura.⁶ Other causes of malignant pleural effusions are mesothelioma, lymphoma, and tumours of the genitourinary and gastrointestinal tracts.⁷ Metastatic malignant pleural effusion is usually a sign of advanced or disseminated disease.

Malignant mesothelioma, a primary tumour of the pleura, should be considered in any patient (male or female) with pleural effusion or pleural thickening, especially if there is a history of exposure to asbestos and chest pain. Mesothelioma usually develops at least 20 years after the initial exposure to asbestos. It is an aggressive tumour, with median survival ranging from eight to 14 months from the onset of symptoms.⁸ The three main histological types are sarcomatoid, epithelioid, and biphasic, with the first type having a worse prognosis.

Outcome—Computed tomography showed a large left pleural effusion and nodular enhancement of the parietal pleura with posterior chest wall invasion (figure). Ultrasound guided percutaneous trucut biopsy confirmed the diagnosis as sarcomatoid mesothelioma. On closer questioning, the patient had been exposed to asbestos for many years during his early working life as a joiner. Unfortunately, he deteriorated shortly after diagnosis and died in hospital.

View larger version (152K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Computed tomography showing a large left pleural effusion (A), posterior chest wall invasion (B), and nodular enhancement of the parietal pleura (C)