MKSAP Quiz: 2-month history of nonproductive cough
A 62-year-old man is evaluated for a 2-month history of nonproductive cough, progressive dyspnea, and fatigue. He reports a 6.8-kg (15-lb) weight loss during this time. He has a 30-pack-year history of smoking. He worked in a navy ship yard 32 years ago. Following a physical exam, chest radiograph, and thoracentesis, what is the most appropriate next step?
A 62-year-old man is evaluated for a 2-month history of nonproductive cough, progressive dyspnea, and fatigue. He reports a 6.8-kg (15-lb) weight loss during this time. He has a 30-pack-year history of smoking. He worked in a navy ship yard 32 years ago. His history is otherwise unremarkable.
On physical examination, vital signs are normal. Oxygen saturation is 94% breathing ambient air. Lung examination findings are consistent with a right pleural effusion. The remainder of the examination is normal. A complete blood count and metabolic profile are normal.
Chest radiograph shows a large right pleural effusion.
Thoracentesis is performed and removes 1200 mL of serosanguineous fluid.
Pleural fluid analysis:
| Cytology | Negative |
| Glucose | 89 mg/dL (4.9 mmol/L) |
| Lactate dehydrogenase | 200 U/L |
| pH | 7.36 |
| Total protein | 3.8 g/dL (38 g/L) |
| Serum lactate dehydrogenase | 235 U/L |
| Serum total protein | 6.2 g/dL (62 g/L) |
Laboratory studies:
| Serum lactate dehydrogenase | 235 U/L |
| Serum total protein | 6.2 g/dL (62 g/L) |
The patient returns 2 weeks later with a recurrent pleural effusion. CT scan of his chest demonstrates a moderate right pleural effusion with no parenchymal or pleural abnormalities noted. Thoracentesis is repeated; pleural fluid analysis is similar to the initial analysis, and cytology is again negative.
Which of the following is the most appropriate next step?
A. Closed pleural biopsy
B. Measure pleural fluid triglycerides
C. Resend a pleural fluid specimen for cytology
D. Thoracoscopy and pleural biopsy
MKSAP Answer and Critique
The correct answer is D. Thoracoscopy and pleural biopsy. This content is available to MKSAP 18 subscribers as Question 92 in the Pulmonary and Critical Care Medicine section. More information about MKSAP is available online.
This patient should be referred for thoracoscopy and pleural biopsy. He has a recurrent exudative pleural effusion. The characterization of pleural fluid as a transudate or exudate helps narrow the differential diagnosis and direct subsequent investigations. An effusion is considered an exudate if any of the following criteria are met: pleural fluid total protein/serum total protein greater than 0.5; pleural fluid lactate dehydrogenase (LDH)/serum LDH greater than 0.6; pleural fluid LDH greater than 2/3 the upper limit of normal for serum LDH. This patient has an exudate. Despite the negative chest radiograph and CT scan, this exudate is concerning for malignancy considering his age, smoking history, and work in a shipyard with potential exposure to asbestos. The cytology of the pleural fluid was negative, but cytology is only 60% sensitive for malignancy.
Closed pleural biopsy is less sensitive than cytology and should not be performed.
A chylous effusion can be suspected by its milky appearance (seen in 50% of patients) and is associated with traumatic and nontraumatic etiologies. Nontraumatic chylous effusion is most commonly due to malignancy (lymphoma, chronic lymphocytic leukemia, metastatic cancer). Traumatic chylous effusions are most commonly associated with thoracic surgical procedures. A pleural fluid triglyceride level greater than 110 mg/dL (1.24 mmol/L) is characteristic of a chylothorax. There is no reason to suspect a chylothorax at this point; thoracoscopic pleural biopsy will be of higher diagnostic yield.
The yield of sending more than two cytology specimens taken on different occasions is low. If cytology is negative and malignancy is still suspected, thoracoscopy with pleural biopsy allows for direct visualization of the pleural surface and has greater than 90% sensitivity for the diagnosis of malignancy.
Key Point
- For patients with negative cytology in whom malignancy is suspected, thoracoscopy with pleural biopsy allows for direct visualization of the pleural surface and has a diagnostic sensitivity for malignant disease of greater than 90%.