Pleural Biopsy

Pleural diseases involve the parietal and visceral pleura and may be of infectious, inflammatory, or malignant origin, often resulting in pleural effusions. The diagnostic evaluation of pleural effusions should include pertinent history, clinical course, and radiographic abnormalities and take into account the patient’s desire to pursue aggressive workup. Initial evaluation begins with a thoracentesis and characterization of the fluid as a transudate or exudate, its appearance, turbidity, and even odor (ie, urinothorax). Further analysis includes chemical, microbiological, cytological, and disease-specific analyses depending on the suspected etiology. Transudative pleural fluid is misclassified as an exudate in up to 25% of cases. ^[1] In order to reduce misclassification, special attention should be paid to the serum-to-pleural protein and serum-to-pleural albumin differences. Differences of more than 3.1 g/dL and more than 1.2 g/dL, respectively, indicate a transudate. ^[1] Rarely, neoplastic pleural diseases can present as a transudate. ^[1] However, 40% of pleural effusions remain undiagnosed after an initial thoracentesis. ^{[2, 3]}

Primary pleural malignancies tend to originate from the parietal pleura and spread to the visceral pleura, while metastatic disease (ie, bronchogenic carcinoma) starts on the visceral pleura and spreads to the parietal pleura. ^{[4, 5]} Contrast-enhanced CT scanning of the thorax is indicated for an undiagnosed exudative effusion to assess for parenchymal abnormalities and the extent of pleural involvement. ^[6] Subsequent pleural biopsy is indicated to evaluate and exclude infectious and malignant etiologies, particularly malignant mesothelioma. ^{[7, 6]} Connective tissue disorders such as rheumatoid disease can also present with pleural involvement, requiring pleural biopsy for diagnosis. In addition, pleural thickening in the absence of pleural effusion may require further histological evaluation. Despite extensive workup, the etiology of pleural effusion remains unclear in nearly 20%-25% of cases. ^{[7, 8]}

Karpathiou et al performed a retrospective analysis of 100 cases of nonspecific pleuritis attributed to benign etiologies and proposed a histopathologic scoring system to further characterize the underlying disease state. The semiquantitative scores were based on the degrees of inflammation, fibrosis, vascular proliferation, hemorrhage, fibrin, edema, and mesothelial hyperplasia on pleural biopsy. The highest overall scores were associated with bacterial and autoimmune diseases, followed by drugs and viruses, while the lowest scores were associated with pneumothorax and cardiac etiologies. Higher degrees of fibrosis and vascular proliferation were associated with bacterial etiologies. The authors propose that the scoring system and patterns seen histologically may assist with identification of the underlying etiology. ^[9]

Once pleural biopsy is indicated, various biopsy techniques are available to diagnose pleural disease. These range from older techniques, such as “blind” or closed pleural biopsy, to image-guided and thoracoscopic biopsy. The latter techniques have higher diagnostic yield and provide better diagnostic sensitivity. In addition, the use of immunohistochemistry provides increased diagnostic accuracy. ^[10]

Indications for pleural biopsy include the following:

• Undiagnosed exudative lymphocytic pleural effusions
• Pleural mass, thickening, or nodularity
• Recurrent pleural effusion of unknown etiology

Cope needles and Abrams needles, as shown in the images below, are most commonly used for blind or closed needle biopsy. This procedure is generally performed in the setting of a large pleural effusion without any imaging other than chest radiography.

Procedure

The patient is positioned and the biopsy site is selected after careful physical examination and review of imaging. Under aseptic measures, lidocaine is injected locally to anesthetize the selected site. A small skin nick is made with a scalpel blade.

The Cope needle with stylet is introduced through the skin incision at the upper surface of the rib in order to prevent neurovascular bundle damage. The needle is advanced until pleural fluid is obtained. The stylet is then removed and the biopsy trocar introduced. A 50-mL syringe is attached with a biopsy needle, which provides a closed system through which pleural fluid may be withdrawn, confirming the location of the biopsy needle in the pleural space. The biopsy needle is turned, with the right-angled projection facing downward. Both the outer cannula and the biopsy trocar are partially withdrawn until the parietal pleura is engaged. Gentle traction is applied to the biopsy trocar with one hand, and the outer cannula is advanced with a rotary motion. This action allows dissection of pleural tissue and intercostal muscle.

The biopsy needle is removed, during which the patient is instructed to make an “EEEEE” sound to minimize the risk of air entry. The biopsy specimen is collected with the attached syringe applying positive pressure. The needle site is observed for bleeding complications, and a pressure dressing is applied to prevent subcutaneous accumulation of pleural fluid.

The Abrams pleural biopsy needle consists of 3 parts, with 2 concentric tubes and a stylet. The outer tube has a trocar point and a deep notch behind the trocar point that can be closed with inner tube rotary movement, allowing cutting of the pleural tissue. The general technique for pleural biopsy with the Abrams needle is similar to that described for the Cope needle.

Blind pleural biopsy is also performed using a Tru-cut needle in the setting of moderate to large pleural effusions, with results that are comparable with those obtained with Abrams and Cope pleural biopsy needles. ^{[11, 12]} However, the Tru-cut needle is generally used with image guidance via ultrasonography or CT scanning.

A newer technique involving retrograde biopsy forceps (Retroforceps, Karl Storz, Tuttlingen, Germany) has been proposed by Wiewiorski et al. The technique, feasibility, and pleural yield were evaluated in a thoracoscopic cadaver study. The surgeon was blinded to the thoracoscopic view, and 20 closed pleural biopsies were performed (10 on the left hemithorax and 10 on the right hemithorax). Nineteen of the 20 biopsy attempts resulted in parietal pleural sampling confirmed thoracoscopically. The authors postulated that this technique may reduce complications related to closed pleural biopsy such as risk of pneumothorax and bleeding complications by utilizing a closed system with suction and optional syringe attachment, as well as a blunt-tipped design. One limitation of the proposed technique is that the biopsy forceps must be removed after each biopsy. This closed technique and ultrasonography-assisted technique requires further evaluation in clinical settings with comparisons to other available pleural biopsy techniques. ^[13]

Complications and precautions

Injury to adjacent organs during pleural biopsy, including liver, kidney, and spleen, is rare. Chest radiography is recommended to exclude immediate postprocedural complications, including pneumothorax. The incidence of pneumothorax with closed needle biopsy is approximately 8%-18%. ^[14]

Hemorrhagic states are considered a relative contraindication to pleural biopsy. The coagulation profile should be corrected prior to any biopsy procedure to minimize the risk of bleeding, including chest wall hematoma and hemothorax.

Diagnostic yield

Needle biopsy of the pleura is useful for establishing the diagnosis of malignant or tuberculous pleural effusion. ^[15] Multiple pleural biopsies are taken to increase the diagnostic yield. Pleural biopsy in combination with pleural fluid cytology improves the yield. ^[7] Needle biopsy of parietal pleural is more valuable in patients with suspected tuberculous effusion than in those with malignant effusion. The initial biopsy may demonstrate granuloma in 50%-80% of patients. ^[16]

Historically, the sensitivity of Abrams biopsies for malignancy ranged between 27% and 60%, and, in the largest review of 2,893 Abrams samples, the diagnostic yield for malignancy was 57%. ^[17] The reported sensitivity is higher for diagnosing tuberculosis with Abrams biopsies, ranging from 67%-92%, in part owing to the diffuse pleural involvement with tuberculous pleuritis. ^[17]

In a 2010 study by Pandit et al using the Abrams needle, pleural biopsy yielded the diagnosis of tuberculosis and malignancy in 90.9% and 63.2% of cases, respectively, and tubercular granuloma were present histopathologically in all cases of tuberculosis. ^[18] Granulomatous pleuritis is not specific for tuberculosis; it is also found in other disease processes, such as fungal infections, sarcoidosis, and rheumatoid disease.

Multiple studies have compared the diagnostic sensitivity of the Cope needle with that of the Abrams needle. ^[19] In a 2006 study of 57 patients with pleural tuberculosis, the diagnostic yield for the Cope needle was 85% compared to 57% for the Abrams needle. However, this finding did not reach statistical significance. The incidence of pneumothorax was higher with the Cope needle than with the Abrams needle. ^[14] In addition, the Cope needle requires more patient cooperation to exhale maximally in order to create less negative intrapleural pressure and thus minimize the risk of pneumothorax.

One study utilized a cytological brush to increase the yield of the closed pleural biopsy procedure with the Cope needle. This technique was superior (91% yield) to that achieved either with pleural fluid cytology (67% yield) or pleural biopsy (58% yield) in malignant pleural effusions. ^[20]

In a 2010 study by James et al, 48 patients with pleural effusion underwent closed pleural biopsy with a Tru-cut biopsy needle. The diagnostic yield of closed pleural biopsy was 62.2% in cases of all exudative pleural effusion, 76.2% in cases of tuberculous pleural effusion, and 85.7% in cases of malignant pleural effusion. ^[12]

In an 8-year prospective study by Báez-Saldaña et al published in 2017, 1034 closed pleural biopsies (Cope or Abrams needles) were performed to evaluate cases of lymphocytic exudative effusions of unknown etiology at a tertiary referral facility in Mexico City. The sensitivity and specificity of closed pleural biopsy for any malignancy were 77% and 98%, respectively, and, for mesothelioma, 81% and 100%, respectively. Of all the samples obtained, 378 (36.56%) biopsies demonstrated nonspecific findings, with 137 (23.34%) corresponding to false-negative results for malignancy. Complication rates were lower than previously reported, at 4.4%, composed of 30 pneumothoraces (11 required chest tube placement), 6 hematomas, 2 vasovagal episodes, and 3 cases of subcutaneous emphysema. Needle selection was not specified in the accuracy analysis, although overall sensitivity was higher than previous reports (up to 68%). ^[21] The sensitivity for any malignancy was on par with the lower end of sensitivity reported for image-guided pleural biopsy (77%). ^{[22, 23]}

Closed pleural biopsy can be considered in patients with suspected diffuse pleural involvement with undiagnosed exudative lymphocytic pleural effusions when image-guided techniques are unavailable or if the patient would be unable to tolerate thoracoscopy. Closed pleural biopsy can also be considered as a first-line diagnostic tool in resource-poor settings with a high prevalence of tuberculosis. ^{[17, 24, 6]} Given the inability to target areas of abnormal pleural thickening or nodularity, the risk of adjacent organ damage, and the frequent complications (ie, pneumothorax) associated with a closed pleural biopsy, ^[14] this procedure is restricted to patients with a large pleural effusion and has largely been replaced with image-guided pleural biopsy.

The procedural yield of pleural biopsy using ultrasonography or CT guidance is increased owing to the ability to precisely target an abnormal area of the pleura. ^{[25, 26, 17]} Ultrasonography is more sensitive in detecting loculated pleural effusions than CT scanning. ^[6] It also has the advantage of providing a real-time approach to the biopsy without radiation. CT guidance allows better visualization of the extent of focal pleural masses, in addition to a clearer delineation of parenchymal pathology. Contrast-enhanced CT scanning with "pleural phase" imaging can also highlight areas of pleural involvement and nodularity to aid in biopsy site selection. ^[17]

Procedure

An area of pleural abnormality is identified using ultrasonography or CT imaging. The patient is then positioned according to the pleural lesions to be biopsied—prone for paravertebral lesions and supine for lateral or anterior lesions. Automated cutting needle devices, as shown in the images below, provide better histological samples than fine-needle aspiration. Three or more samples are generally obtained to ensure adequate pleural tissue for histopathological diagnosis.

Utilizing a sterile technique, a local anesthetic agent is administered. The large coaxial needle with stylet is then advanced under ultrasound or CT guidance into the pleural lesion, as depicted in the images below.

The stylet is then removed manually, and the cutting needle device is placed with a tip proximal to the biopsy site to allow the “throw” of device. The tissue is obtained with the activation of the biopsy device (see image below). Multiple pleural biopsies can be collected while keeping the coaxial outer needle in place.

A 2015 prospective study by Koegelenberg et al involving 100 patients outlined a sequential approach that utilized ultrasonography to assess pleural involvement, assist with site selection, and determine biopsy technique. If a pleural mass was identified, fine-needle aspiration was performed with rapid on-site evaluation. If the findings were negative, a cutting needle was used. In the setting of pleural thickening, needle selection was determined by thickness (10-24 mm for Abrams and >25 mm for a cutting needle). If no thickening was noted, an Abrams needle was used. This method increased diagnostic yield from 31% to 89.7% for malignancy and up to 90% for all diagnoses. ^[27]

Selection between needles and image-guided techniques depend on the feasibility of each technique considered for the individual patient. Variable effusion sizes, pleural thickening, patient cooperation, positioning, and visibility under ultrasonographic guidance influence selection of the appropriate technique. If no pleural effusion is present, selection of the Abrams needle for ultrasonographic or CT guidance is eliminated.

Diagnostic advantages and limitations

Image-guided pleural biopsy is safe and allows for the ability to biopsy abnormal pleural tissue, to increase diagnostic yield independent of pleural thickening, and to obtain samples in areas closer to the midline and diaphragm where malignant deposits are more likely to occur. ^{[28, 29]} The cutting biopsy needle appears to be more sensitive for malignancy than fine-needle aspiration, with a sensitivity of 91% in the diagnosis of mesothelioma. ^[30] Previous studies demonstrate a sensitivity of up to 88% for image-guided cutting needle sensitivity in the diagnosis of malignancy ^{[17, 30, 22, 31, 32]} and a sensitivity of nearly 100% in the diagnosis of mesothelioma if the lesion is at least 20 mm in any direction. ^[27]

Image guidance can also be used with the Abrams needle, with a reported sensitivity of 60%-77.4% with ultrasonography-assisted site selection and 87.5% with CT-guided Abrams pleural needle biopsy. ^{[33, 34, 35]} Koegelenberg et al in 2010 and 2015 reported diagnostic yields with ultrasonography-assisted Abrams needle biopsy of 80%-90% for pleural tuberculosis and 83%-90% for pleural malignancies. ^{[36, 27]}

The diagnostic yield of CT-guided pleural biopsy also increases with pleural thickening of 1 cm or greater. Under these circumstances, the sensitivity of cutting needle biopsy increases to 87% and the sensitivity of CT-guided Abrams needle biopsy up to 95%. ^{[26, 31, 34]}

The complication rates are lower for image-guided biopsy than for blind pleural biopsy, particularly in relation to pneumothorax. ^{[30, 37]} This protective effect was also demonstrated in a comparison between ultrasonography- and CT-guided biopsies, with fewer pneumothoraces in the ultrasonography group (5.5% vs 14.7%), although patients were not randomized. ^{[25, 17]} Patients who are unable to hold their breath during the biopsy, either because of underlying lung pathology or positive pressure ventilation, are more likely to develop the complications of pneumothorax and lung injury.

Tekin et al analyzed 181 patients who underwent cutting-needle pleural biopsies (100 CT-guided, 81 ultrasonography-guided) and demonstrated similar technical success rates (99.8% for ultrasonography-guided and 97% for CT-guided). There were no significant differences between the groups for pathologic results, 54.1% malignant, 43.6% benign, and 2.2% with insufficient material. No significant difference was noted in complication rates, but ultrasonography-guided procedures were 50% shorter (average duration, 17 minutes vs 35 minutes), performed more often in patients with increased comorbidities, cost less, and obviated the need for ionizing radiation. ^[38]

Ultrasonography-assisted cutting-needle biopsies can also be performed by experienced pulmonologists without a decrease in diagnostic sensitivity. ^[39] Ultrasonography-guided pleural biopsy remains an option for patients who are unable to tolerate thoracoscopy or in whom thoracoscopy failed, with a diagnostic sensitivity of 94% for all diagnoses and 87% for malignancy in a small series of 50 patients. ^[40] In patients who are unable to undergo thoracoscopy, recent studies demonstrate comparable diagnostic results with image-guided pleural biopsy, although thoracoscopy remains the criterion standard.

Thoracoscopy has been used for over 100 years, and pleuroscopy has gained increased acceptance as one version of the criterion standard for diagnosis of pleural effusions, with a diagnostic yield of up to 95% in malignant pleural disease. ^{[41, 42]} Compared with previous biopsy techniques, pleuroscopy can be both diagnostic and therapeutic, allowing direct visualization of pleural pathology, adhesiolysis, pleurodesis, and chest tube placement. Pleuroscopy is performed by a pulmonologist in the endoscopy suite or in the operating room with local anesthesia or under moderate sedation with appropriate cardiopulmonary monitoring.

Instruments

Pleuroscopy can be performed with either rigid or semirigid instruments with a single port of entry or two ports. The semirigid pleuroscope used for the procedure is similar to a bronchoscope in design and handling. The difference is that the pleuroscope shaft has two sections—the larger proximal rigid portion and flexible distal end, which moves with the handle. The pleuroscope has a working channel to accommodate the biopsy forceps and other instruments. A trocar allows passage of the scope through the chest wall. The diameters of instruments used for the procedure vary: trocars (7-11 mm), optics (6-10 mm), biopsy forceps (2.8-6 mm), and cryoprobes (1.9-2.4 mm). ^{[42, 43]}

Procedure

Pleuroscopy is performed with a semirigid bronchoscope that functions similarly to a flexible bronchoscope. Continuous cardiopulmonary monitoring with electrocardiography and pulse oximetry is conducted. An intravenous narcotic (fentanyl) and benzodiazepine (midazolam) are used for moderate sedation. Alternatively, general anesthesia with intubation can also be considered.

The patient is placed in the lateral decubitus position, with the affected side facing upward.

The procedure can be initiated through an intercostal incision, or a pneumothorax can be introduced prior to the procedure, with drainage of the pleural fluid. The pneumothorax allows the lung to collapse and move away from the chest wall to facilitate trocar insertion. The site of trocar insertion depends on the suspected pathology. If malignancy is suspected, the trocar is advanced over the sixth intercostal space at the midaxillary line. ^[44] Otherwise, the fourth space is preferred, given the better visualization of the lung apex from this position. For diagnostic purposes, a single-puncture technique is used that involves a 1- to 2-cm incision in the midaxillary line between the fourth and seventh intercostal spaces of the chest wall.

Multiple parietal pleural biopsies can be obtained through the single port of entry with the flexible biopsy forceps. A double-puncture technique is preferred for adhesiolysis, lung biopsy, and complex loculated fluid drainage. A small-bore catheter or chest tube is placed at the conclusion of the procedure and can be removed after the lungs are fully inflated.

Limitations

Pleural biopsy samples obtained with the semirigid pleuroscope are small, given the size of the flexible biopsy forceps. Obtaining deeper parietal pleural specimens may be limited since the biopsy forceps lack mechanical strength. Obtaining multiple (5–10) pleural biopsies from abnormal areas and taking several samples from the same location repeatedly ensures adequate biopsy depth. ^[41]

To overcome the small size of pleural biopsy samples, Thomas et al performed a safety and feasibility study of cryoprobe pleural biopsies, demonstrating no increased risk of complications, larger biopsy samples, less crush artifact, and comparable diagnostic yield. ^{[17, 42, 45]} Similar results have been reproduced by others since. ^[46]

A 2016 prospective study by Wurps et al compared different biopsy techniques, including rigid forceps, semirigid forceps, and cryobiopsy. Medical thoracoscopy was performed with a rigid thoracoscope (11 mm, Storz, Tuttlingen, Germany) after ultrasonographic site selection and introduction of a pneumothorax under fluoroscopic guidance. Pleural biopsy samples were taken sequentially by rigid forceps, semirigid forceps, and cryobiopsy techniques. Unblinded pathologic evaluation included size (mm²) and quality of the biopsy (the presence of fat, indicating a deep biopsy of high quality). Eighty patients were included, with a total of 408 biopsies (205 rigid, 104 flexible, and 99 cryobiopsies). The mean surface area of biopsy samples collected with rigid forceps was 22.6 ± 20.4 mm², flexible forceps was 7.1 ± 9.3 mm², and cryoprobe was 14.4 ± 12.8 mm². A deep biopsy was obtained in 63% of rigid biopsies, 39.5% with flexible forceps, and 49.5% with cryoprobe. The diagnostic yields for rigid, flexible, and cryobiopsies were 98.7%, 92.5%, and 91.3%, respectively. Pathologic evaluation of cryoprobe pleural biopsy samples showed less tissue damage in an overall very good quality consistent with prior results described for lung biopsies. The authors conclude that cryobiopsy cannot replace rigid forceps biopsy but is a safe method with high diagnostic value, providing larger and deeper specimens over flexible forceps during medical thoracoscopy. ^{[47, 43]}

Similar findings have been published for the evaluation of malignant pleural mesothelioma, albeit fewer cases owing to its rarity, demonstrating consistently larger, deep biopsies, less crush artifact, and improved diagnostic sensitivity (4/4 cases) compared to conventional instruments (1/4 cases). ^[48]

Complications

In a combined analysis of 47 studies with 4,756 patients, major complications were noted in 1.8% of cases, minor complications in 7.8%, and mortality in 0.34%. Major complications include hemorrhage, empyema, pneumonia, tumor seeding along the procedure tract, and bronchopleural fistula causing postoperative pneumothorax or prolonged air leaks. Minor complications include subcutaneous emphysema, minor bleeding, local wound infection, hypotension during the procedure, and transient fever. ^{[17, 41, 49]} A meta-analysis of 17 studies and 755 patients by Agarwal et al in 2013 reported similar rates, with a pooled analysis demonstrating major and minor complication rates of 1.5% and 10.5%, respectively, and no mortality. ^{[50, 49]}

The major concern of the procedure is pleural hemorrhage from underlying intercostal blood vessels. Immediate pressure using forceps and a small piece of gauze can be applied to control bleeding. If bleeding is significant, an additional incision should be considered to access the pleural cavity in order to perform tissue cauterization. If bleeding is not controlled with direct pressure and cauterization, ligation of the bleeding vessels with endoclips should be considered. Ongoing bleeding may require thoracotomy.

Video-assisted thoracic surgery (VATS) allows additional access to lung tissue and operative interventions, including lung biopsies, lobectomy, pericardial window placement, and empyema drainage. VATS is carried out by surgeons in an operating room under general anesthesia using single-lung ventilation with double-lumen endotracheal intubation.

Instruments

VATS is performed with rigid endoscopic equipment, including a light source, an endoscopic camera with a video monitor, and a recording system (see images below). ^[51]

The different telescopes have various angles, from 0° for direct visualization to oblique (30° or 50°) and periscopic (90°) viewing. Various sizes of trocars are deployed as a means of introduction for the rigid telescope through the chest wall.

Procedure

VATS is performed after placing a double-lumen endotracheal tube or a single-lumen tube with a bronchial blocker. The patient is usually placed in the lateral decubitus position with the affected area exposed. However, the procedure can also be performed in the supine position.

Using sterile techniques, 1-3 incisions, each 0.5-1 cm, are placed. The initial port site is created by incising the skin with the scalpel, then using a hemostat to bluntly spread the fascia and muscle layers until the pleural cavity is entered. The first incision placement should be at the maximum distance from the site of dissection or inspection to allow better visualization. Surgical interventions are made over the rib to prevent any injury to the neurovascular bundle. One of the incisions is usually located at a site suitable for the placement of the chest tube at the conclusion of the procedure. The second incision is placed more cephalad in a more anterior or posterior position depending on area of interest to be biopsied.

A port is placed through the first incision and a camera is inserted. The second incision is created with direct visualization of the camera from the inside. The pleural space is then inspected and areas of interest are biopsied at multiple sites after a thorough inspection is completed. Biopsy samples can be collected with biopsy forceps or other endoscopic instruments. After completion of the biopsy, the camera is rotated between port sites to check for hemostasis. A chest tube is then placed. The lung is then reinflated, and the remaining port site is closed with absorbable sutures.

Postprocedural care

Chest tubes are removed when air leaks have resolved and drainage is at acceptable levels. Chest X- Ray is performed post-procedure and after removal of the chest tube to assess for pneumothorax.

Limitations

Several factors can limit this diagnostic intervention, including marked coagulopathy, an inability to obtain unilateral lung ventilation, or inability of the patient to tolerate the procedure because of hypoxemia. Adhesions represent a relative contraindication depending on their location and density.

Complications

The reported complications of VATS are similar to those seen with pleuroscopy, including mesothelioma tract metastasis. Mesothelioma has been reported to spread along the tracks of surgical biopsy incisions, chest tubes, and biopsy needles. The reported incidence of 22% for tract metastasis was higher with surgical biopsy compared to 4% with needle biopsy in one study of 100 patients. ^[52] Prophylactic radiation may be helpful, although this is controversial. ^{[53, 54]}

Closed pleural biopsy should be reserved for suspected diffuse processes in resource-poor settings with a high prevalence of tuberculosis where image-guided pleural biopsy is unavailable and operators can maintain procedural competency. Contrast-enhanced CT highlights involved areas of the pleura and identifies parenchymal abnormalities, which should be obtained prior to image-guided biopsy or thoracoscopy. Image-guided pleural biopsy should be the primary method of investigation when thoracoscopy is unavailable for undiagnosed exudative pleural effusions, especially in the setting of pleural thickening, owing to its diagnostic yield, low complication rates, and availability. Thoracoscopy (pleuroscopy or VATS) remains the criterion standard in the evaluation of pleural disease owing to its consistent safety profile, diagnostic yield, and therapeutic advantages, but it may not be appropriate in all patients.