Malignant pleural effusion (MPE) is a condition where an abnormal amount of fluid collects between the two layers of tissue, called the pleura, that line the lungs and the chest wall. The pleural space normally contains only a small amount of fluid, but the presence of cancer cells in this fluid or the pleura itself can lead to a significant buildup. Analyzing this fluid is necessary to confirm the diagnosis, determine the cancer’s origin, and guide subsequent treatment decisions.
Obtaining the Sample
The procedure used to collect the fluid for analysis is called thoracentesis, which serves both diagnostic and therapeutic purposes. A physician uses a thin needle or catheter to access the pleural space and draw out the fluid.
This process is typically performed while the patient is sitting up and is guided by ultrasound imaging to ensure accurate positioning. Ultrasound guidance helps pinpoint the fluid pocket, minimizing the risk of complications such as puncturing the lung.
For diagnosis, a small sample (50 to 100 milliliters) is collected for laboratory tests. If the effusion is large and causing shortness of breath, a larger volume, up to 1.5 liters, may be removed for immediate symptom relief.
Initial Fluid Characterization
Once the fluid is collected, the first step in the laboratory is a general biochemical analysis to categorize the effusion as either transudate or exudate. Transudates are typically caused by systemic issues like heart failure, resulting from an imbalance of pressure in the blood vessels.
Malignant effusions are almost always classified as exudates, which are caused by local factors such as inflammation, infection, or malignancy itself. The distinction between the two is commonly made using Light’s criteria, which compares the levels of protein and lactate dehydrogenase (LDH) in the pleural fluid to those in the blood serum. An effusion is considered an exudate if the pleural fluid protein to serum protein ratio is greater than 0.5, or the pleural fluid LDH to serum LDH ratio is greater than 0.6, or the pleural fluid LDH is greater than two-thirds of the upper limit of normal serum LDH.
Beyond these criteria, other markers in the fluid can provide additional clues pointing toward malignancy. For example, a low glucose level in the fluid (typically less than 60 mg/dL) and a low pH (below 7.30) are often seen in malignant effusions. Elevated LDH levels in the fluid also suggest an inflammatory process or high tumor burden, warranting the more specific testing needed to search for cancer cells.
Identifying Malignancy
The definitive diagnosis of MPE relies on identifying cancer cells within the fluid, a process that begins with cytopathology, or cytology. This involves examining a fluid sample under a microscope for the characteristic features of malignant cells. Cytology is a straightforward way to confirm the diagnosis, but its sensitivity can vary widely, ranging from about 40% to 90%.
If the initial cytology result is negative despite a strong suspicion of cancer, the fluid is often subjected to more advanced techniques. One challenge is differentiating between true cancer cells and reactive mesothelial cells, which can look similar but are present due to benign inflammation. To overcome this, pathologists use immunohistochemistry (IHC), a method that applies specific antibodies to the cells to identify proteins or biomarkers on their surface. The pattern of these protein markers helps determine the specific type of cancer and, often, its primary site of origin, such as lung or breast.
Molecular Testing
The most significant recent advancement involves molecular testing of the fluid, which analyzes the DNA and RNA of the cells. This testing can identify specific genetic mutations or biomarkers, such as EGFR, ALK, or PD-L1, that are driving the cancer’s growth. These molecular tests are particularly valuable because they can detect cancer-driver mutations even in samples where the number of malignant cells is low, sometimes resulting in a positive molecular result despite a negative cytology. The ability to profile these genetic markers in pleural fluid is transforming the treatment landscape for cancers like non-small-cell lung carcinoma.
Guiding Clinical Management
The comprehensive analysis of the pleural fluid directly influences the patient’s clinical management, guiding both local symptom relief and systemic cancer treatment. For symptom control, the fluid analysis helps determine the best approach for managing the fluid accumulation that causes shortness of breath. A low pleural fluid pH, for instance, is associated with a poorer response to pleurodesis, a procedure used to fuse the pleura layers together to prevent fluid reaccumulation.
In cases where pleurodesis is unlikely to be successful, or if the patient’s lung cannot fully expand, an indwelling pleural catheter (IPC) may be inserted for long-term, at-home drainage. The specific findings from the molecular analysis are now routinely used to direct systemic therapy, moving beyond traditional chemotherapy. For example, the identification of a specific mutation, like an EGFR gene alteration, directs the use of targeted therapy drugs that specifically block the activity of that mutation.
Similarly, the presence of the PD-L1 protein, identified through IHC, can indicate that the cancer is a candidate for immunotherapy. The analysis also carries prognostic value, helping to inform the patient and the care team about the likely course of the disease. A malignant effusion often signifies advanced disease, and specific markers, such as low glucose and pH levels, are associated with a shorter survival time. Therefore, the fluid analysis provides a roadmap for personalized treatment, ensuring the most effective application of available therapies.