Malignant Pleural Effusion: Evaluation and Diagnosis

Pulmonary Disease Board Review. 2019 August;16(2)

David Hsia, MD
Health Sciences Associate Clinical Professor, Division of Respiratory and Critical Care Physiology and Medicine, Harbor-UCLA Medical Center, Torrance, CA

Ali I. Musani, MD
Professor of Medicine and Surgery, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Denver, CO

References

1. Antony VB, Loddenkemper R, Astoul P, et al. Management of malignant pleural effusions. Eur Respir J. 2001;18:402-419.

2. Society AT. Management of malignant pleural effusions. Am J Respir Crit Care Med. 2000;162:1987-2001.

3. Clive AO, Kahan BC, Hooper CE, et al. Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score. Thorax. 2014;69:1098-1104.

4. Taghizadeh N, Fortin M, Tremblay A. US hospitalizations for malignant pleural effusions: data from the 2012 National Inpatient Sample. Chest. 2017;151:845-854.

5. Yang TS, Hsia DW, Chang DW. Patient- and hospital-level factors associated with readmission for malignant pleural effusion. J Oncol Pract. 2018;14:e547-e556.

6. Ost DE, Niu J, Zhao H, et al. Quality gaps and comparative effectiveness of management strategies for recurrent malignant pleural effusions. Chest. 2018;153:438-452.

7. Miserocchi G. Physiology and pathophysiology of pleural fluid turnover. Eur Respir J. 1997;10:219-225.

8. Sahn SA. State of the art. The pleura. Am Rev Respir Dis. 1988;138:184-234.

9. Khaleeq G, Musani AI. Emerging paradigms in the management of malignant pleural effusions. Respir Med. 2008;102:939-948.

10. Das DK. Serous effusions in malignant lymphomas: a review. Diagn Cytopathol. 2006;34:335-347.

11. Qian Q, Zhan P, Sun WK, et al. Vascular endothelial growth factor and soluble intercellular adhesion molecule-1 in lung adenocarcinoma with malignant pleural effusion: correlations with patient survival and pleural effusion control. Neoplasma. 2012;59:433-439.

12. Kraft A, Weindel K, Ochs A, et al. Vascular endothelial growth factor in the sera and effusions of patients with malignant and nonmalignant disease. Cancer. 1999;85:178-187.

13. Meyer PC. Metastatic carcinoma of the pleura. Thorax. 1966;21:437-443.

14. Light RW, Hamm H. Malignant pleural effusion: would the real cause please stand up? Eur Respir J. 1997;10:1701-1702.

15. Chernow B, Sahn SA. Carcinomatous involvement of the pleura: an analysis of 96 patients. Am J Med. 1977;63:695-702.

16. Musani AI, Haas AR, Seijo L, et al. Outpatient management of malignant pleural effusions with small-bore, tunneled pleural catheters. Respiration. 2004;71:559-566.

17. Roberts ME, Neville E, Berrisford RG, et al; Group BPDG. Management of a malignant pleural effusion: British Thoracic Society Pleural Disease Guideline 2010. Thorax. 2010;65 Suppl 2:ii32-40.

18. Estenne M, Yernault JC, De Troyer A. Mechanism of relief of dyspnea after thoracocentesis in patients with large pleural effusions. Am J Med. 1983;74:813-819.

19. Brown NE, Zamel N, Aberman A. Changes in pulmonary mechanics and gas exchange following thoracocentesis. Chest. 1978;74:540-542.

20. Wang LM, Cherng JM, Wang JS. Improved lung function after thoracocentesis in patients with paradoxical movement of a hemidiaphragm secondary to a large pleural effusion. Respirology. 2007;12:719-723.

21. Huggins JT, Doelken P, Sahn SA. The unexpandable lung. F1000 Med Rep. 2010;2:77.

22. Lan RS, Lo SK, Chuang ML, Yang CT, Tsao TC, Lee CH. Elastance of the pleural space: a predictor for the outcome of pleurodesis in patients with malignant pleural effusion. Ann Intern Med. 1997;126:768-774.

23. Lentz RJ, Lerner AD, Pannu JK, et al. Routine monitoring with pleural manometry during therapeutic large-volume thoracentesis to prevent pleural-pressure-related complications: a multicentre, single-blind randomised controlled trial. Lancet Respir Med. 2019;7:447-455.

24. Porcel JM, Alvarez M, Salud A, Vives M. Should a cytologic study be ordered in transudative pleural effusions? Chest. 1999;116:1836-1837.

25. Ryu JS, Ryu ST, Kim YS, et al. What is the clinical significance of transudative malignant pleural effusion? Korean J Intern Med. 2003;18:230-233.

26. Boersma WG, Stigt JA, Smit HJ. Treatment of haemothorax. Respir Med. 2010;104:1583-1587.

27. Light RW, Erozan YS, Ball WC. Cells in pleural fluid. Their value in differential diagnosis. Arch Intern Med. 1973;132:854-860.

28. Garcia LW, Ducatman BS, Wang HH. The value of multiple fluid specimens in the cytological diagnosis of malignancy. Mod Pathol. 1994;7:665-668.

29. Swiderek J, Morcos S, Donthireddy V, et al. Prospective study to determine the volume of pleural fluid required to diagnose malignancy. Chest. 2010;137:68-73.

30. Abouzgheib W, Bartter T, Dagher H, Pratter M, Klump W. A prospective study of the volume of pleural fluid required for accurate diagnosis of malignant pleural effusion. Chest. 2009;135:999-1001.

31. DeMaio A, Clarke JM, Dash R, et al. Yield of malignant pleural effusion for detection of oncogenic driver mutations in lung adenocarcinoma. J Bronchology Interv Pulmonol. 2019;26:96-101.

32. Grosu HB, Arriola A, Stewart J, et al. PD-L1 detection in histology specimens and matched pleural fluid cell blocks of patients with NSCLC. Respirology. 2019 Jun 17. doi: 10.1111/resp.13614.

33. Koegelenberg CF, Diacon AH. Pleural controversy: close needle pleural biopsy or thoracoscopy-which first? Respirology. 2011;16:738-746.

34. McLaughlin KM, Kerr KM, Currie GP. Closed pleural biopsy to diagnose mesothelioma: dead or alive? Lung Cancer. 2009;65:388-389.

35. Miyoshi S, Sasada S, Izumo T, et al. Diagnostic utility of pleural fluid cell block versus pleural biopsy collected by flex-rigid pleuroscopy for malignant pleural disease: a single center retrospective analysis. PLoS One. 2016;11:e0167186.

36. Vanderlaan PA, Yamaguchi N, Folch E, et al. Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer. Lung Cancer. 2014;84:39-44.

37. Albanna AS, Kasymjanova G, Robitaille C, et al. Comparison of the yield of different diagnostic procedures for cellular differentiation and genetic profiling of non-small-cell lung cancer. J Thorac Oncol. 2014;9:1120-1125.

38. Tremblay A RS, Berthiaume L, and Michaud G. Natural history of asymptomatic pleural effusions in lung cancer patients. J Bronchol. 2007;14:98-100.

39. Porcel JM, Gasol A, Bielsa S, et al. Clinical features and survival of lung cancer patients with pleural effusions. Respirology. 2015;20:654-659.

40. Feller-Kopman DJ, Reddy CB, DeCamp MM, et al. Management of malignant pleural effusions. An official ATS/STS/STR clinical practice guideline. Am J Respir Crit Care Med. 2018;198:839-849.

41. Grosu HB, Molina S, Casal R, et al. Risk factors for pleural effusion recurrence in patients with malignancy. Respirology. 2019;24:76-82.

42. Psallidas I, Kanellakis NI, Gerry S, et al. Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis. Lancet Oncol. 2018;19:930-939.

Predictors of Recurrence and Prognosis

Not all MPEs will progress in size or become symptomatic, and predicting which patients will develop symptoms from their effusions is difficult. Pleural effusions will develop in only a minority of patients with lung cancer, and only a small subset will progress and require therapeutic intervention.^38,39 Therefore, management guidelines for malignant pleural effusions discourage empiric intervention for patients with small, asymptomatic effusions.⁴⁰ However, patients with larger, symptomatic effusions are more likely to have significant and rapid fluid recurrence. In a series of 988 symptomatic patients undergoing drainage, 30% had fluid recurrence within 15 days, 40% within 30 days, 45% within 60 days, and 48% within 90 days.⁴¹ Factors associated with fluid recurrence included radiographic size of the effusion, requirement for a larger amount of fluid to be initially drained, and higher pleural fluid lactate dehydrogenase (LDH) level. Negative cytology was associated with lower likelihood for recurrence.

Prognostication of life expectancy is another important clinical assessment which impacts medical decision-making when weighing the risk and benefits of different palliation options. Patient performance status, pleural fluid LDH, serum neutrophil-to-lymphocyte ratio, and tumor origin are independently associated with prognosis in a validated scoring system (Table 2).³ In this study, the overall median survival of patients with MPE was approximately 4.5 months, while the median survival for patients with mesothelioma was 11.3 months, 6.6 months for breast cancer, and 2.5 months for lung cancer and other malignancies. When stratified based on the combination of these 4 variables, patients in the high-risk group had a median survival of just 44 days compared to 130 days for the moderate-risk group and 319 days for the low-risk group. Additional, more complex prediction systems for survival and response to MPE therapies are now emerging and may provide clinicians and patients with additional information useful in medical decision-making.⁴²

Conclusion

MPEs represent advanced stage disease and frequently adversely affect a patient’s quality of life. Ideal therapeutic options, discussed in the second part of this review, should effectively palliate symptoms, provide long-term relief, be minimally invasive with few side effects, minimize hospitalization and reliance on medical assistance, and be cost-effective.