The pleural cavity is an almost virtual space between the mesothelium of the parietal and visceral pleura, containing a modest amount of fluid sufficient to facilitate movement between the two membranes.
Its increase, called pleural effusion, is due either to over production, mainly in congestive heart failure, or to reduced reabsorption, mostly from lymphatic obstruction during neo plasms. In summary, the most common conditions causing pleural effusion are heart failure, tumors, tuberculosis, and pulmonary embolism.
In the case of suspected pleural effusion, the patient’s clinical picture can be correctly framed by radiological and/ or ultrasound examinations to confirm its presence. In this case, thoracentesis is performed for both diagnostic and therapeutic purposes.
The distinction between exudate (increased capillary permeability or decreased lymphatic reabsorption), transudate (increased hydrostatic pressure or decreased oncotic pressure), and chylous effusion (caused by trauma or neoplasm, usually lymphoma involving the thoracic duct) is a crucial diagnostic step.
Transudates are generally bilateral because they have a systemic etiology.
Exudates are frequently unilateral, associated with disorders that increase capillary permeability or interfere with ipsilateral lymphatic reabsorption.
Effusions from malignant neoplasms behave ambiguously: unlike what we might expect, they are unlikely to be exudative due to the concomitant presence of congestive heart failure.
The main causes of a transudate are congestive heart failure, liver cirrhosis, hypoproteinemia (e.g., nephrotic syn drome), infections (e.g., bacterial pneumonia, tuberculosis, or other granulomatous diseases, such as sarcoidosis and histoplasmosis; viral or mycoplasma pneumonias), neoplasms (bronchogenic carcinoma, metastatic carcinomas, lymphomas, mesotheliomas), non-infectious inflammatory diseases (rheumatoid arthritis, systemic lupus erythematosus [SLE]), accumulation of fluid of extrapleural origin (e.g., from pancreatitis with increased lipid-lowering lipid), and exudate (from pancreatitis with increased pancreatic lipase and amylase, from esophageal rupture with increased pancreatic enzymes and acid pH, and finally, urinothorax).
The first step in the biochemical evaluation of the effusion is to determine its origin, either transudative or exudative. For this purpose, Light’s criteria have been widely used in clinical practice over the past four decades (Table 1).

Table1. Biochemical analysis performed on the pleural fluid and related interpretative criteria
In their initial work, Light et al. reported a sensitivity of 99% and a specificity of 98% in identifying the type of effusion, although in subsequent studies the specificity was lower (65–86%). Despite this limitation, Light’s criteria are considered superior to clinical judgment alone in characterizing effusions.
Macroscopic Evaluation and Cellular Analysis
In pleural effusions of transudative origin, the fluid is generally clear, light yellow, whereas in those of probable exudative origin (neoplastic or infected), the fluid is turbid (Table 2). The appearance of the fluid may be hemorrhagic, due to a sample collection not performed well or bleeding. In the latter case, the color of the fluid may vary from red to brown depending on the time elapsed between the start of the hemorrhage and the collection.

Table2. Macroscopic and cytometric analysis of the pleural fluid and related interpretative criteria
In the case of neoplastic or chylous effusion, the fluid may be milky. Table 3 describes the differential characteristics of chylous and pseudochylous effusion.

Table3. Main characteristics of chylous and pseudochylous pleural effusions and related interpretative criteria
Normally, the volume of fluid in the pleural cavity ranges between 4.1 and 12.7 mL, the total cellularity is between 1395 and 3794 × 106/L, macrophages between 64% and 80%, lymphocytes between 18% and 36%, neutrophils between 0% and 1%, and mesothelial cells between 0% and 2%.
In pleural effusions of exudative origin, on the other hand, the cell count is greater than 1000 × 106/L. In this condition, neutrophilia greater than 50% is indicative of an inflammatory process of bacterial etiology (e.g., parapneumonic effusion). A lymphocytosis higher than 50% is associated with tubercular infection, chylous effusions due to mechanical damage of the lymphatic system, and lymphoproliferative diseases. Lymphocyte characterization is especially useful in exudative effusions; in these cases, immuno-phenotyping can distinguish between benign and malignant lymphoproliferative diseases.
Eosinophilia (>10%) occurs in conditions as diverse as pneumothorax, pulmonary embolism, traumatic hemothorax, and Churg-Strauss syndrome.
The count of red blood cells distinguishes between serous effusion and hemothorax. The latter may be secondary to trauma, pulmonary embolism, and neoplasia.
Total cellularity is useful in the differential diagnosis between exudates and transudates: in the latter, approximately 80% have a cellularity of less than 1000 × 106/L cells; cellularities greater than 1000 × 106/L are usually associated with parapneumonic effusions.
Biochemistry Light’s criteria include assaying total protein and LDH on pleural fluid and serum to calculate the ratio. Table 1 summarizes the biochemical criteria for identifying an exudate with greater accuracy than using total protein alone.
The pH has a high positive prognostic value in non- pneumococcal pneumonia. The presence of creatinine or urea indicates the presence of urine in pleural fluid. C-reactive protein (CRP) of pleural fluid may be more sensitive than blood protein in diagnosing non-pneumococcal pneumonia.
The usefulness of assaying certain tumor-associated bio logical markers in pleural fluid is controversial. For example, the literature reports the case of a patient with a marked increase in prostate-specific antigen (PSA), which proved to be decisive in establishing the diagnosis of metastatic prostate cancer. The patient presented with severe anemia, peripheral edema, and pleural and pericardial effusions, but no neoplastic cells.
A milky pleural fluid suggests the presence of a chylothorax, which is always due to obstruction of the thoracic duct for mainly neoplastic or traumatic reasons. However, it is useful to distinguish this situation from a pseudo- chylothorax, which is usually due to rheumatoid pleurisy, tuberculosis, or myxedema. In these cases, triglyceride and chylomicron detection may be helpful; table 3 summarizes the criteria for the differential diagnosis between the two situations.
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