⇓Malignant pleural effusions are a common clinical problem in patients with neoplastic disease. In one post mortem series, malignant effusions were found in 15% of patients who died with malignancies 1. Although there have been no epidemiological studies, the annual incidence of malignant pleural effusions in the United States is estimated to be >150,000 cases (table 1⇓) 2–17. Malignant pleural effusion is also one of the leading causes of exudative effusion; studies have demonstrated that 42–77% of exudative effusions are secondary to malignancy 18, 19.



Fig. 1.— 
Malignant pleural effusions: sensitivity (%) of different biopsy methods (cytological and histological results combined). Presented is a prospective simultaneous comparison (n=208).





Fig. 2.— 
Diagnostic sensitivity of cytology (□) and medical thoracoscopy (![Graphic][1] ) in malignant pleural effusions. n-numbers are as follows: lung cancer, 67; non-lung primary, 154; mesothelioma, 66; total, 287.





Fig. 3.— 

View this table:

Table 1— 
Incidence of malignant pleural effusions (MPEs)



Nearly all neoplasms have been reported to involve the pleura. In most studies, however, lung carcinoma has been the most common neoplasm, accounting for approximately one-third of all malignant effusions. Breast carcinoma is the second most common. Lymphomas, including both Hodgkin's disease and non-Hodgkin's lymphoma, are also an important cause of malignant pleural effusions. Tumours less commonly associated with malignant pleural effusions include ovarian and gastrointestinal carcinomas. In 5–10% of malignant effusions, no primary tumour is identified 12, 13. The incidence of mesothelioma varies according to the geographical location.

Post mortem studies suggest that most pleural metastases arise from tumour emboli to the visceral pleural surface, with secondary seeding to the parietal pleura 1, 20. Other possible mechanisms include direct tumour invasion (in lung cancers, chest wall neoplasms, and breast carcinoma), haematogenous spread to parietal pleura, and lymphatic involvement. A malignant tumour can cause a pleural effusion, both directly and indirectly. …

 [1]: F2/embed/inline-graphic-1.gif

https://erj.ersjournals.com/content/erj/18/2/402.full.pdf

Management of malignant pleural effusions.

This review describes the usefulness of monitoring the activity level of lactate dehydrogenase (LDH) and its isoenzyme pattern as indicators of pathological conditions in the lungs, such as cell damage or inflammation. Cytoplasmatic cellular enzymes, like LDH, in the extracellular space, although of no further metabolic function in this space, are still of benefit because they serve as indicators suggestive of disturbances of the cellular integrity induced by pathological conditions. Since LDH is an enzyme present in essentially all major organ systems, serum LDH activity is abnormal in a large number of disorders. Although the increase in total serum LDH activity is rather nonspecific, it is proposed that measurement of LDH activity levels and its isoenzyme pattern in pleural effusion and, more recently, in bronchoalveolar lavage fluid may provide additional information about lung and pulmonary endothelial cell injury.

https://erj.ersjournals.com/content/erj/9/8/1736.full.pdf

Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation

Real-Time Chest Ultrasonography: A Comprehensive Review for the Pulmonologist

Levels of tumor markers in pleural effusions may help to establish the diagnosis of pleural malignancy, but the precise diagnostic value of each marker remains unclear. The aim of this study was to assess the diagnostic value of five common pleural fluid tumor markers, carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, cancer antigen (CA) 15-3, CA 19-9, and CA 125, and to review the literature from the past 15 years. Pleural fluid samples were collected prospectively from 116 patients and assayed for CEA, CYFRA 21-1, CA 15-3, CA 19-9, and CA 125 levels. A MEDLINE search of the English-language literature from the past 15 years was also done. Effusions were classified as benign or malignant on the basis of their definitive pathologic or cytologic diagnoses. The levels of all pleural tumor markers were statistically significantly higher in the malignant group than in the benign group. The marker with the highest accuracy was CEA (85.3%); CA 15-3, CYFRA 21-1, and CA 19-9 had similar accuracies (75.2%, 72.4%, and 71.5%, respectively), and CA 125 had the lowest accuracy (40.5%). On univariate analysis, tumor-marker combinations did not result in a greater accuracy than that of CEA alone. On multivariate logistic regression, CA 15-3 and CYFRA 21-1 were significant predictors of malignancy. Among the nine reports in the literature comparing 11 different tumor markers, CEA, CA 15-3, and CYFRA 21-1 yielded the best results. We conclude that pleural fluid analysis should include CEA for the diagnosis of malignancy. CA 15-3 and CYFRA 21-1 may serve as alternative options.

Diagnostic Value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 Assays in Pleural Effusions: Analysis of 116 Cases and Review of the Literature

Background: The role of tumour markers such as carbohydrate antigen (CA) 125, CA 15-3, CA 19-9 and CYFRA 21-1 (a fragment of cytokeratin 19) in differentiating malignant pleural effusions (MPE) from benign effusions is not yet clear. Methods: After a systematic review of English language studies, sensitivity, specificity and other measures of accuracy of pleural concentrations of CA 125, CA 15-3, CA 19-9 and CYFRA 21-1 or their combinations in the diagnosis of MPE were pooled using random effects models. Summary receiver operating characteristic curves were used to summarise overall test performance. Results: Twenty-nine studies met the inclusion criteria for the analysis. The summary estimates of the sensitivity and specificity of these tumour markers were as follows: CA 125, 0.48/0.85; CA 15-3, 0.51/0.96; CA 19-9, 0.25/0.96; CYFRA 21-1, 0.55/0.91 for diagnosing MPE. The estimated summary receiver operating characteristic curves showed that the performance of pleural CA 125 and CA 19-9 measurement in the diagnosis of MPE was limited, whereas that of CA 15-3 and CYFRA 21-1 was better. When two or more of the above four tumour markers were combined, or combined with carcinoembryonic antigen, the sensitivity and specificity were all increased to different extents. Conclusions: The current evidence does not recommend using one tumour marker alone for the diagnosis of MPE, but the combination of two or more tumour markers seems to be more sensitive. The results of tumour marker assays should be interpreted in parallel with clinical findings and the results of conventional tests.

https://thorax.bmj.com/content/thoraxjnl/63/1/35.full.pdf

Boris Stastny

Papers

Diagnosis of Pleural Effusions: Experience With Clinical Studies, 1986 to 1990