Investigation of pleural effusion: comparison between fibreoptic thoracoscopy, needle biopsy and cytology

Twenty-eight patients with exudative pleural effusion have been investigated by fibreoptic thoracoscopy, Abrams needle biopsy and pleural fluid cytology. Sixteen patients had previously had negative pleural biopsies and cytology. Twenty effusions were malignant (16 mesothelioma, four metastatic carcinoma), seven were due to nonspecific inflammation and in one case no abnormality was found. The diagnostic yield for all three techniques combined was 85%, for thoracoscopy alone 65%, Abrams biopsy 60% and cytology 45%. In 12 patients presenting without previous investigation all eight malignant effusions were correctly diagnosed by at least one of the techniques with individual sensitivities of 75% for thoracoscopy, 63% for Abrams and 38% for cytology. Of the 16 patients who had previously had negative investigations 12 had malignant effusions, nine (75%) of which were diagnosed by a combination of the techniques. In this group, the individual sensitivities were 58% for both thoracoscopy and Abrams and 50% for cytology. A correct diagnosis of malignancy was made by a combination of needle biopsy and cytology in 75% of patients with previous investigations and 88% of those without. Fibreoptic thoracoscopy added only two diagnoses of malignancy to those obtained by Abrams and cytology. The limitations of the technique render it unsuitable for routine investigation of pleural effusions.     

Pleural Lavage: A Novel Diagnostic Approach For Diagnosing Exudative Pleural Effusion

Patients with pleural effusions frequently present a diagnostic and therapeutic challenge. The diagnosis is based on the interpretation of the results of thoracentesis or pleural biopsy. When a malignant tumor metastasizes to the pleura, tumor cells can be seeded over the mesothelial surface or in the subserous layer. In the former situation, tumor cells are abundant in pleural fluid, but in the latter, few malignant cells are exfoliated into the pleural cavity, and microscopic deposits may not be visualized at thoracoscopy. Pleural lavage cytologic study at the time of thoracoscopy has not been studied. The purpose of this study was to assess the value of thoracoscopic pleural lavage as an adjuvant in the diagnostic workup of patients with exudative pleural effusions. Fifty patients with exudative pleural effusions were investigated by pleural fluid cytologic findings, Abram's pleural biopsy, thoracoscopy, and pleural lavage cytologic findings. After aspiration of all pleural fluid, 300 mL saline was instilled into the pleural cavity and then recovered for cytologic analysis. The final diagnoses were 32 malignant (64%), 15 tuberculous (30%), and 3 idiopathic (6%) effusions. In the malignant group, thoracoscopic biopsy had the highest yield (94%) followed by lavage cytologic analysis (84%), fluid cytologic analysis (62%), and biopsy with Abram's needle (50%). The sensitivity of combined thoracoscopy and lavage cytologic analysis was 96%. In the patients with tuberculous pleuritis, the yield from the pathologic examination of the biopsy specimen was 93% with thoracoscopy and 60% with the Abrams needle. The diagnostic yield with cytologic analysis on pleural lavage fluid is significantly higher than that on pleural fluid. This is probably because the cells in the lavage fluid are fresher and better preserved than those in the regular pleural fluid, which may have undergone degenerative changes, yielding false-negative results. Pleural lavage cytologic analysis should be performed in patients with suspected malignant pleural effusion who are subjected to diagnostic thoracoscopy, because it may provide additional information to thoracoscopic biopsy. Accepted for publication: 21 November 2000     

胸腔积液端粒酶和癌胚抗原测定对良恶性胸腔积液诊断价值对比研究

目的 研究胸腔积液端粒酶活性在良恶性胸腔积液中的鉴别诊断价值,并与癌胚抗原（CEA）进行比较。方法 用聚合酶链反应－酶联免疫吸附分析法（PCR－ELISA）检测胸腔积液端粒酶活性,用酶免疫分析法（EIA）检测胸腔积液CEA水平。根据最终诊断结果,65例患者分成2组：（1）非恶性胸腔积液组：35例,（2）恶性胸腔积液组：30例。并将端粒酶活性检测结果与胸腔积液CEA测定结果进行比较。结果 非恶性胸腔积液中端粒酶阳性2例（5．7％）,恶性胸腔积液中阳性27例（90％）,端粒酶活性测定诊断恶性胸腔积液的灵敏度为0．90,特异度0．94,阳性预测值0．93,阴性预测值0．92,正确率0．92。CEA诊断灵敏度为0．60,特异度0．89,阳性预测值0．82。阴性预测值0．72,正确 率0．75。结论 胸腔积液端粒酶活性鉴别良恶性胸腔积液的诊断效能明显优于CEA测定,可作为一种诊断恶性胸腔积液的辅助手段。     

Thoracoscopy with pleural brushing. A new diagnostic method for pleural diseases

Pleural brushing can be performed under thoracoscopic examination. The combined use of all three methods of diagnosis (macroscopy, biopsy, cytology) achieved optimal diagnostic results. From September 1980 to October 1981 we have performed 150 thoracoscopies for pleural effusions, while the results of conventional pleural cytology and biopsy were negative. In 108 cases pleural brushing and biopsy were both performed. The diagnosis was in 37 cases non malignant disease states associated with effusions and in 71 cases tumoural effusions. Among the 37 cases of non malignant diseases states associated with effusions were 6 mechanical effusions, 27 inflammatory processes, 4 infectious processes. Among the 71 cases of tumoural effusions were 3 benign pleural lipomas, 50 metastatic carcinomas, 18 carcinomatous mesotheliomas. We studied the diagnostic accuracy of pleural brushing: in non malignant diseases pleural brushing show the non tumoural features of the process, in metastatic tumours biopsy was positive in 80% of the cases; pleural brushing in 78% of cases; taken together they allowed the diagnosis in 86% of the cases, in carcinomatous mesotheliomas biopsy was positive in 82.3%, pleural brushing in 78%; taken together they allowed the diagnosis in 89% of the cases. Pleural brushing allows a rapid cytological diagnosis, enhances the histological results and may be used to get cellular material in areas dangerous to biopsy.     

胸膜活检对原因不明的渗出性胸腔积液的诊断价值

目的观察胸膜活检术在渗出性胸腔积液诊断中的价值。方法对146例渗出性胸腔积液患者行胸膜活检，同时取胸水及痰送检抗酸杆菌及癌细胞。结果146例胸膜活检第一次活检成功率71．9％，特异性病理诊断92例，病理诊断阳性率63％。恶性胸腔积液胸膜活检阳性率58％，胸水细胞学检查阳性率22％，痰找癌细胞阳性率16％。结核性胸腔积液胸膜活检阳性率66．6％，痰找抗酸杆菌阳性率5．2％。结论胸膜活检是一项安全、简单、有效的胸膜疾病的重要的内科确诊手段。     

78例老年胸积液联检加胸部CT的诊断价值

目的探讨老年人胸腔积液的病因。方法选择78例患者做胸部CT检查,同时取胸腔积液做PCR,结核抗体,胸膜活检,细胞学检查。结果胸部CT检查,确定有胸腔积液78例,肺部和纵膈有病变60例,无肺部、纵膈等病变18例。结论PCR,结核抗体在诊断结核性胸腔积液中阳性率高,RCP特异性高,胸膜活检与细胞学检查在两种疾病检测标准不同,阳性率及特异性均高。     

Malignant pleural mesothelioma in the southwestern part of The Netherlands

This report is the result of an analysis of the medical records of 124 patients presenting with a malignant pleural mesothelioma. Information about asbestos exposure was available in 104 of them, which appeared to be positive in 95 (91%). The median duration of exposure was 34 yrs. The median latent period was 41 yrs. The median survival was 11 months while different ways of treatment could not prolong survival. The most common radiologic findings were pleural effusions, while in some patients contralateral effusions or pleural thickening was found. Pleural plaques or asbestosis were seen in a minority of the patients. In this series a relatively high percentage of mixed type mesotheliomas was found (56%). Large biopsies will often show both epithelial and connective tissue type elements. Concerning diagnostic procedures we recommend beginning with cytology of pleural fluid, which can easily be obtained together with an Abrams biopsy. If this does not give a definite diagnosis thoracoscopy or thoracotomy will be indicated.     

Video-assisted thoracoscopic surgery using single-lumen endotracheal tube anesthesia

BACKGROUND: Most general thoracic surgeons use double-lumen endotracheal tube (DLET) anesthesia for all video-assisted thoracoscopic surgery (VATS). We evaluated a single-lumen endotracheal tube (SLET) for VATS for drainage of pleural effusions and pleural biopsies. METHODS: A consecutive series of patients with recurrent pleural effusions underwent VATS using an SLET and only one incision. Operations were accomplished via one 2-cm incision using a 5-mm rigid thoracoscope and mediastinoscopic biopsy forceps for directed pleural biopsies. A working area was accomplished with low tidal volumes. RESULTS: There were 376 patients (191 women). The indications for VATS were a nondiagnosed or benign pleural effusion in 294 patients, and a malignant effusion in 82 patients. Two hundred eight patients underwent biopsy of the parietal pleura, and mean operative time was 17 min. Adequate visibility was obtained in all. When compared to preoperative cytology, VATS was more sensitive (45% compared to 99%, p < 0.001), had a higher negative predictive value (56% compared to 99%, p < 0.001), and was more accurate (67% compared to 99%, p < 0.001). Forty-seven percent of patients with a history of cancer had false-negative preoperative cytology results. Complications occurred in seven patients (2%), and there were three operative deaths (none related to the operative procedure). CONCLUSION: VATS using SLET and only one incision is possible, and it affords excellent visualization of the pleural space, allowing pleural biopsies and talc insufflation. It avoids the risk, time, and cost of a DLET. It is significantly more sensitive and accurate than preoperative cytology, and it should be considered as the diagnostic and therapeutic procedure of choice in patients with recurrent pleural effusions.     

The role of Abrams percutaneous pleural biopsy in the investigation of exudative pleural effusions

INTRODUCTION: Blind percutaneous pleural biopsy has traditionally been performed to investigate the etiology of exudative pleural effusion in which the initial thoracentesis has been nondiagnostic. In view of the increasing use of image-guided and thoracoscopic pleural biopsies, this study examines the role of blind Abrams pleural biopsy in the investigation of pleural effusion in a large urban hospital. METHOD: Patients undergoing blind Abrams needle biopsy between January 1997 and 2003 were identified from the hospital pathology database. The case notes and pathology records of these patients were analyzed retrospectively. All patients had presented to respiratory teams with an exudative pleural effusion and had initial nondiagnostic thoracentesis. RESULTS: Seventy-five patients undergoing blind biopsy were identified. Pleural tissue was obtained in 59 biopsies (79%), with no statistically significant difference in pleural yield between respiratory specialist registrars (equivalent to pulmonary fellows in training) and senior house officers/preregistration house officers (equivalent to junior residents and interns, respectively) performing the biopsy (chi(2) test, p = 0.43). When up to three samples were obtained per episode, sufficient pleural tissue was obtained in 18 of 25 patients (72%) compared to 80% (32 of 40 patients) in whom four to six samples were taken (chi(2) test, p = 0.55 [not significant]). For all diagnoses, blind biopsy had a sensitivity of 38%, which rose to 43% when reviewing patients in whom sufficient pleural tissue was obtained (for malignant diagnosis alone, sensitivity values were 43% and 51%, respectively; specificity, 100%; negative and positive predictive values, 51%). No fatalities were reported, and pneumothorax was seen in eight patients (11%), with only two patients requiring specific intervention. CONCLUSIONS: Blind Abrams needle biopsy obtaining pleural tissue was diagnostic in approximately 50% of patients presenting with malignant effusion in the sample, and can be performed safely by all grades of medical staff with due attention to technique and supervision. The data support the continued use of the Abrams needle in the investigation of malignant pleural disease.     

Combination chemotherapy in patients with malignant pleural effusions from non-small cell lung cancer : cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support

OBJECTIVES: Malignant pleural effusions develop frequently in patients with non-small cell lung cancer (NSCLC), and the prognosis for these patients is very poor. We evaluated the role of systemic chemotherapy for patients with malignant pleural effusions from NSCLC. METHODS: We analyzed 34 patients who were found to have malignant pleural effusions in the course of diagnosis of 118 patients enrolled in three consecutive clinical trials on advanced NSCLC assessing combination chemotherapy of cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony-stimulating factor support. The objective response in the malignant pleural effusion was evaluated by CT scans every course with the response criteria of the Japan Lung Cancer Society. RESULTS: All patients had adenocarcinoma. The pleural effusion showed a complete response in 13 patients, a partial response in 7 patients, and no response in 14 patients. In the assessment of the efficacy of the treatment for the measurable primary or metastatic lesions, there was a partial response in 25 patients, no change in 8 patients, and progressive disease in 1 patient. The response rate in pleural effusions was 58.8%, and overall response in mensurable lesions was 73.5%. The median time to response and duration of response for pleural effusions were 54 days and 151 days, respectively. The median survival time and 1-year survival rates were 362 days and 48.5%, respectively. CONCLUSIONS: Both the response rate and survival data in this retrospective study suggest a high degree of activity of this combination chemotherapy in patients with malignant pleural effusions from NSCLC.     

Pleural fluid pH in malignant effusions. Diagnostic, prognostic, and therapeutic implications

STUDY OBJECTIVE: To determine whether the measurement of pleural fluid pH in malignant effusions has diagnostic use, predicts survival, and has therapeutic implications. DESIGN: A prospective comparison of cytologic examinations and pleural biopsy results, survival, and response to chemical pleurodesis with tetracycline in patients with normal-pH (7.30 or greater) and low-pH (less than 7.30) malignant pleural effusions. SETTING: Academic medical center, university referral hospital, city hospital, and Veterans Administration hospital. PATIENTS: Sixty patients with malignant pleural effusions, proven at either initial thoracentesis by cytologic examination or within 4 months of initial thoracentesis by repeat thoracentesis, thoracotomy, or autopsy, were followed until death. INTERVENTION: Twenty-one patients, 12 with normal pleural fluid pH and 9 with low pleural fluid pH, were treated with tube thoracostomy and intrapleural tetracycline for symptomatic, recurrent pleural effusions. MAIN RESULTS: The 20 patients with low-pH malignant effusions had a significantly greater positivity on initial pleural fluid cytologic evaluation, a shorter mean survival, and a poorer response to tetracycline pleurodesis compared with 40 patients with normal-pH malignant effusions. CONCLUSIONS: Determination of pleural fluid pH in malignant effusions provides a rational approach to further diagnostic testing, prognostic information, and a rationale for palliative treatment.     

A comparative study of pleurodesis using talc slurry and bleomycin in the management of malignant pleural effusions

Differing success rates of various pleurodesis agents have been reported in the management of malignant pleural effusions. A randomized clinical trial was conducted to compare the efficacy of two commonly used agents, talc and bleomycin, for the pleurodesis of malignant pleural effusions. Methodology : Inclusion in the study required proof of a malignant pleural effusion by fluid cytology or pleural biopsy. Exclusion criteria included trapped lung, loculated effusions, recurrent effusions and life expectancy < 1 month. Five grams of talc or 1 unit per kilogram bodyweight of bleomycin mixed in 150 mL of normal saline was administered via tube thoracostomy after complete drainage of the pleural effusion in each patient. Treatment success was defined as the absence of recurrent pleural effusion on the chest radiograph 1 month after pleurodesis. Results : Treatment success was achieved in 16 out of 18 patients (89%) in the talc slurry group versus 14 out of 20 patients (70%) in the bleomycin group (P = 0.168). Fever and pain were the only side‐effects of pleurodesis in both groups. Conclusion : These results indicate that talc slurry is as effective as bleomycin in preventing early recurrence of malignant pleural effusions. Pleurodesis with talc instead of bleomycin can result in significant cost savings.     

The role of thoracoscopy in the evaluation and management of pleural effusions

Diagnostic thoracoscopy is indicated in every patient where the usual investigations (including biochemistry, cytology, bacteriology, occasionally needle biopsy of the pleura) do not achieve a precise diagnosis. The percentage of so-called “idiopathic” effusions, amounting to approximately 20% in many published series, can be reduced to 4% after thoracoscopy. The sensibility of thoracoscopic biopsy reaches 93–97% of malignant or tuberculous pleural effusions. The procedure requires a short hospitalization of about 36 hr, and complications are rare. Therapeutic thoracoscopy is frequently performed in chronic, malignant, recurrent effusions in order to achieve a pleurodesis by means of a talc poudrage under visual control. The efficacy of the poudrage in the published randomized studies is better than tetracycline. About 90% of patients are cured, the effusion being totally suppressed. Side effects are rare if the quantity of talc does not exceed 10 ml.     

A comparative study of the polymerase chain reaction and conventional procedures for the diagnosis of tuberculous pleural effusion.

Preliminary reports by ourselves and others suggest that amplification of mycobacterial DNA by the polymerase chain reaction (PCR) is a sensitive and rapid diagnostic test for tuberculosis. We recently described a PCR assay with a 336 bp repetitive sequence specific for Mycobacterium tuberculosis as the DNA target, which gave encouraging results in culture-positive smear-negative clinical specimens. In the present prospective study of patients with pleural effusions we compared PCR of the pleural fluid with conventional procedures. 84 adult patients with pleural effusions were divided into 4 groups. In group A (44 patients), M. tuberculosis was detected by culture of pleural fluid, pleural biopsy or extrapleural source. In group B (6 patients), tuberculous infection was confirmed by histology (group A excluded). Group C (3 patients) had clinical evidence of tuberculosis. Group D (31 patients) had no evidence of active M. tuberculosis infection. Analysis of the pleural fluid confirmed a sensitivity for PCR of 81%. The sensitivity of pleural fluid culture, culture of pleural biopsy, and histology of biopsy was 52.8%, 69.8% and 77.3% respectively. There were however 7 PCR positive results within group D; 6 of these were in patients with malignant effusions. We conclude that for the diagnosis of M. tuberculosis PCR is more sensitive than laboratory culture as determined by the analysis of pleural fluids. Positive PCR results among patients with malignant effusions may be false-positives or the result of latent tuberculous infections. PCR should remain an investigational procedure until prospective studies in high and low prevalence areas have critically evaluated the specificity of the assay.     

Needle biopsy of the pleura in Nigeria

The results of needle biopsy of the pleura carried out on 200 patients are presented. Biopsy was diagnostic in 60% of tuberculous pleural effusions and in 74% of cases of malignant effusions. The histological appearance of chronic fibrosis was seen in 34%, of which half were subsequently found to have tuberculosis.     

Note on the complications of pleural needle biopsy: neoplastic seeding of the wall (apropos of 300 effusions and 440 puncture biopsies)]

Out of 440 pleural biopsies done with Abrams or Castelain needle, performed over 11 years in 300 pleural effusions, only 14 incidents of accidents occurred. There were 9 minor ones (intrapleural bleeding, subcutaneous emphysema, pneumoserosa by aspiration). Neoplastic graft along the biopsy tract was observed in 5 cases, of which 4 were primitive malignant mesotheliomas and one a primitive appearing neoplastic pleurisy. The risk of parietal neoplastic seeding runs high in malignant mesothelioma, considering that 11 such cases were included in this series of biopsied patients. This risk is not specific to plaural biopsy and can be encountered in simple thoracentesis. This complication therefore is not a contra-indication to needle biopsy as it is only observed in diseases beyond surgical redemption.     

Vasoactive mediators (VEGF and TNF-alpha) in patients with malignant and tuberculous pleural effusions

OBJECTIVE: Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific mitogen that promotes angiogenesis, vascular hyperpermeability, and vasodilatation by autocrine mechanisms involving nitric oxide (NO). This study was undertaken to determine the potential role of VEGF in the pathogenesis of pleural effusions, and its relationship with tumour necrosis factor (TNF)-alpha and NO in the pleural fluid and serum of patients with tuberculous and malignant pleural effusions. METHODOLOGY: Pleural fluid and serum (SE) VEGF, TNF-alpha and NO levels were measured in 30 patients with exudative pleural effusion (15 with malignancies and 15 with tuberculosis). Control pleural fluid was obtained from 10 patients with transudative pleural effusion due to congestive heart failure and control serum samples were obtained from 10 healthy individuals. VEGF and TNF-alpha were measured by enzyme-linked immunosorbent assay and NO by a colorimetric method. Pleural biopsy, cytology or microbiological methods were used to make the final diagnosis. RESULTS: In patients with exudative pleural effusions, the mean pleural fluid and serum VEGF levels and their ratios (P < 0.0001 for all) and TNF-alpha levels (P < 0.01, P < 0.0001 and P < 0.05) were significantly elevated compared to those with transudative pleural effusion. In malignant effusions, pleural fluid and serum VEGF levels were significantly elevated (P < 0.001 and P < 0.0001) while pleural fluid, and serum levels and their ratios of TNF-alpha (P < 0.001, P < 0.01 and P < 0.05) were significantly lower than those in tuberculosis. NO levels did not distinguish between tuberculous and malignant effusions. CONCLUSIONS: In patients with malignant pleural effusions, levels of VEGF were significantly higher, while levels of TNF-alpha were significantly lower, than in patients with tuberculous effusions. In malignant pleural effusions, the elevated pleural fluid levels of VEGF and TNF-alpha are noteworthy. Our data support the hypothesis that blockade of VEGF, might benefit cancer patients with recurrent ascites or pleural fluid accumulation.     

The usefulness of pleural biopsy in benign or malignant pleurisy

Retrospective studies of pleural biopsy, cytology and ADA in pleural effusion were performed in 116 patients with pleural effusion between 1980 and 1988. Pleural malignant disease was diagnosed in 25 patients (75.8%) by cytology, in 19 patients (57.6%) by pleural biopsy. Thus, cytology should be performed first in patients with pleurisy. Both of cytologic study and CEA in pleural effusion were negative in 3 cases of squamous cell carcinoma. Tuberculous pleuritis was diagnosed in 24 patients (50.0%) by pleural biopsy, in 5 patients (10.4%) by isolation of Mycobacterium tuberculosis. Both pleural biopsy and adenosine deaminase activity (ADA) were examined in 19 cases of tuberculous pleuritis and ADA was elevated in 16 patients (84.2%). These data suggested that pleural biopsy was useful for diagnosis of pleuritis and the combination of cytology, tumor markers and ADA with biopsy improved diagnostic rates of pleuritis.     

Pleural puncture needle biopsy]

Two hundred and thirty patients with pleurisy had pleural biopsy done by Castelain needle. This examination was positive in 85.7% of cases in tuberculous pleurisies and in 50% of cases in neoplastic pleurisies. The yield of needle pleural biopsy is higher in these two cases than in bacteriology and pleural cytology. The low rate of incidents and accidents (5.5%) widens the scope of needle pleural biopsy in non purulent pleurisy.     

Use of a panel of tumor markers (carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 15-3, and cytokeratin 19 fragments) in pleural fluid for the differential diagnosis of benign and malignant effusions

STUDY OBJECTIVE: The diagnostic value of tumor markers in pleural fluid is subject to debate. The aim of this study was to evaluate the diagnostic performance of several tumor markers in common use for detecting malignant pleural disease. DESIGN: Blinded comparison of four tumor markers in pleural fluid with a confirmatory diagnosis of malignancy by pleural cytology or thoracoscopic biopsy. SETTING: Two teaching hospitals in Spain. PATIENTS AND METHODS: A total of 416 patients (166 with definite malignant effusions, 77 with probable malignant effusions, and 173 with benign effusions) were enrolled. Among them, there were 42 patients recruited from one of the participant centers with thoracoscopic facilities, who had false-negative fluid cytology findings and malignancy confirmed by medical thoracoscopy. Tumor markers in pleural fluid were determined either by electrochemiluminescence immunoassay (carcinoembryonic antigen [CEA], carbohydrate antigen 15-3 [CA 15-3], cytokeratin 19 fragments [CYFRA 21-1]) or microparticle enzyme immunoassay (cancer antigen 125 [CA 125]) technologies. Cutoff points that yielded 100% specificity (ie, all patients with benign effusions had levels below this cutoff) were selected for each marker. RESULTS: Malignant pleural effusions (PEs) had higher levels of pleural fluid markers than did effusions due to benign conditions. At 100% specificity, a pleural CEA > 50 ng/mL, CA 125 > 2,800 U/mL, CA 15-3 > 75 U/mL, and CYFRA 21-1 > 175 ng/mL had 29%, 17%, 30%, and 22% overall sensitivities, respectively. The combination of the four tumor markers reached 54% sensitivity, whereas the combined use of the cytology and the tumor marker panel increased the diagnostic yield of the former by 18% (95% confidence interval, 13 to 23%). More than one third of cytology-negative malignant PEs could be identified by at least one marker of the panel. CONCLUSIONS: No single pleural fluid marker seems to be accurate enough as to be introduced in the routine workup of PE diagnosis. However, a tumor marker panel may represent a helpful adjunct to cytology in order to rule in malignancy as a probable diagnosis, thus guiding the selection of patients who might benefit from further invasive procedures.