What lab test is ordered from the fluid of a pleural effusion to determine malignancy (cancer)?

From the Guidelines

Cytology is the primary lab test ordered from pleural fluid to determine if a pleural effusion is malignant. When a pleural effusion is suspected to be malignant, the fluid is collected through thoracentesis and sent for cytological examination, where pathologists examine the cells under a microscope to identify cancer cells. This test has a sensitivity of approximately 60-70% for detecting malignancy, though the yield may increase with larger fluid volumes and repeat testing 1.

Key Points to Consider

• The British Thoracic Society guideline recommends submitting 25–50 mL of pleural fluid for cytological analysis in patients with suspected malignant pleural effusion (MPE) 1.
• Additional tests that may complement cytology include pleural fluid tumor markers (such as CEA, CA 15-3, or CA 125), flow cytometry for suspected lymphomas, and immunohistochemistry to help identify the primary tumor type 1.
• If cytology results are negative but malignancy is still suspected, a pleural biopsy may be necessary to obtain tissue for definitive diagnosis.
• Pleural fluid cytology is particularly valuable because it is relatively non-invasive compared to tissue biopsy and can often provide diagnostic information that guides treatment decisions for patients with malignant pleural effusions 1.

Important Considerations for Clinicians

• The diagnostic yield of pleural fluid cytology varies depending on tumor type, tumor load, sample quality, expertise of cytologist, and availability of specific ancillary tests 1.
• Analyzing larger volumes of pleural fluid may improve diagnostic sensitivity in MPE, although there appears to be a threshold 1.
• The combined method of direct smear/cytospin and cell block preparations has been shown to offer additional value compared to smear slides alone 1.

From the Research

Lab Tests for Malignant Pleural Effusion

• Cytological examination of pleural fluid is a fast, efficient, and non-invasive diagnostic method to determine if a pleural effusion is malignant 2.
• The diagnostic sensitivity of pleural fluid cytology for malignant pleural effusions (MPE) is around 58.2% 3.
• Cytologic analysis using a stained smear and cell block preparation can provide a diagnosis in about 55% of malignant effusions 4.

Types of Malignant Pleural Effusions

• Metastatic carcinomas, including those from lung, breast, and ovarian tumors, are the most common cause of malignant pleural effusions 2.
• Malignant mesothelioma is another type of malignant pleural effusion, but it is particularly challenging to diagnose using cytologic examination 4.
• The sensitivity of pleural fluid cytology varies by primary tumor type, with higher sensitivity for lung adenocarcinoma and ovarian cancer, and lower sensitivity for mesothelioma and lung squamous cell carcinoma 3.

Diagnostic Yield of Pleural Fluid Cytology

• The diagnostic yield of pleural fluid cytologic examination can be improved with repeated pleural fluid cytologic specimens and when combined with a percutaneous pleural biopsy 5.
• Cloudy appearance of pleural fluid and yellow/gold pleural fluid can reduce the odds of false negative pleural cytology, while pleural thickening on computed tomography scan can increase the risk of false negative results 6.