What pleural fluid studies should be ordered if there's a concern for malignancy?

From the Guidelines

When evaluating pleural fluid for suspected malignancy, order cytology, cell count with differential, protein, LDH, glucose, pH, and tumor markers such as CEA, CA 15-3, CA 125, or CA 19-9, and consider sending at least 25-50 mL of pleural fluid for cytological analysis, as recommended by the British Thoracic Society guideline for pleural disease 1. The most recent and highest quality study, published in 2023, suggests that sending a larger volume of pleural fluid for analysis can improve the diagnostic yield, but even smaller volumes can be useful if that's all that is available 1. Key tests to consider include:

• Cytology, which is the most important test for detecting malignant cells, with a sensitivity of 60-90% 1
• Cell count with differential, to evaluate for lymphocyte predominance, which is common in malignant effusions 1
• Protein, LDH, glucose, and pH, to assess for exudative characteristics and low glucose and pH, which are often seen in malignant effusions 1
• Tumor markers, such as CEA, CA 15-3, CA 125, or CA 19-9, to help identify the primary tumor site 1 If initial cytology is negative but clinical suspicion remains high, consider proceeding to more invasive procedures like thoracoscopy or pleural biopsy, which can increase diagnostic yield to over 90% 1. It's also important to note that the diagnostic yield of cytology depends on sample preparation, the experience of the cytologist, and the tumor type, with the highest diagnostic yields retrieved in patients with adenocarcinoma 1. In terms of specific recommendations, the British Thoracic Society guideline suggests that 25-50 mL of pleural fluid should be submitted for cytological analysis in patients with suspected malignant pleural effusion (MPE) 1. Ultimately, the choice of tests and procedures will depend on the individual patient's presentation and clinical suspicion, as well as the availability of resources and expertise.

From the Research

Pleural Fluid Studies for Malignancy

If there's a concern for malignancy, the following pleural fluid studies should be ordered:

• Cytological examination of pleural fluid to check for cancer cells 2, 3, 4
• Biochemical tests, such as total protein, lactate deaminase (LDH), and adenosine deaminase (ADA) 5
• Differential cell count to determine the type of cells present in the pleural fluid 5
• Pleural fluid cell block studies to further evaluate the cells present in the fluid 6

Additional Diagnostic Tests

If the initial tests are inconclusive, the following additional diagnostic tests may be ordered:

• Medical thoracoscopy, which is considered the gold standard for diagnosing unexplained pleural effusions 2, 6
• Ultrasound-guided closed pleural biopsy, which has been shown to be as effective as thoracoscopic pleural biopsy in some cases 6
• CT or ultrasound-guided pleural biopsy to obtain pleural tissue for further examination 5
• Molecular diagnosis, such as nucleic acid amplification or Xpert MTB/RIF, if tuberculous pleural effusion is suspected 5

Factors to Consider

When ordering pleural fluid studies, the following factors should be considered:

• The type of tumor suspected, as the sensitivity of pleural fluid cytology varies depending on the tumor type 3
• The amount of fluid drained, as larger amounts may increase the likelihood of detecting malignancy 3
• The presence of contralateral effusion, which may decrease the risk of malignancy if the initial cytology is negative 3