Evaluation of pleural fluid cytology for the diagnosis of malignant pleural effusion: a retrospective cohort study

Our plain-English summary of Evaluation of pleural fluid cytology for the diagnosis of malignant pleural effusion: a retrospective cohort study, by L. Pairman, L.E.L. Beckert, M. Dagger, et al (Internal Medicine Journal, 2022).

The study

• Authors: L. Pairman, L.E.L. Beckert, M. Dagger, M.J. Maze
• Journal: Internal Medicine Journal
• Published: 2022;52(7):1154-1159
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Cytological examination of pleural fluid has good specificity, but imperfect sensitivity for the diagnosis of malignant pleural effusion (MPE). Published estimates of sensitivity vary and predictors of false negative cytology are not well established.

Aims: To estimate pleural fluid cytology sensitivity and identify risk factors for false negative cytology.

Methods: We conducted a retrospective cohort study of patients who had cytology testing of pleural fluid at Christchurch Hospital, New Zealand, from July 2017 to October 2019. Data on clinical and pleural fluid characteristics were collected. MPE was defined by positive pleural fluid cytology, tissue histology or multidisciplinary meeting consensus. We estimated sensitivity of the first pleural cytology assessment. We performed multivariate logistic regression to ascertain patient groups at greatest risk of false negative results.

Results: Initial pleural fluid cytology was diagnostic in 117 of 156 patients, providing a sensitivity (95% confidence interval (CI)) of 75.0% (67.4-81.6%). The sensitivity was 79.0% (66.8-88.3%) for lung cancer, 91.3% (72.0-98.9%) for breast cancer and 33.3% (95% CI 11.8-61.6%) for mesothelioma. Cloudy appearance of pleural fluid (odds ratio (OR) 0.12; 95% CI 0.03-0.54) and yellow/gold pleural fluid (OR 0.24; 95% CI 0.06-0.96) reduced the odds of false negative pleural cytology. Pleural thickening on computed tomography scan (OR 3.3; 95% CI 1.2-9.4) was a risk factor for false negative cytology.

Conclusion: Sensitivity of pleural fluid cytology was greatest in primary lung and breast cancer, and lowest in mesothelioma. Clinicians should be alert to false negative results when suspecting mesothelioma or if pleural thickening is present.

© 2022 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.

In plain English

This retrospective cohort study at Christchurch Hospital, New Zealand, measured how often the first test of fluid around the lungs (cytology) found cancer in 156 patients with malignant pleural effusion, 2017–2019. The first test was positive in 117 of 156 (sensitivity 75.0%; 95% CI 67.4–81.6%). Sensitivity was 79.0% (95% CI 66.8–88.3%) for lung cancer (49 of 62), 91.3% (72.0–98.9%) for breast cancer (21 of 23) and 33.3% (11.8–61.6%) for mesothelioma (5 of 15). In the final model, cloudy and yellow/gold fluid were linked to lower odds of a false negative, and pleural thickening on CT to higher odds (odds ratio 3.3; 95% CI 1.2–9.4). Recorded asbestos exposure (12 patients) was initially linked to higher odds of a false negative (odds ratio 3.6; 95% CI 1.1–12.1); in the final model it was not statistically significant (odds ratio 2.5; 95% CI 0.65–9.7). The authors concluded cytology remains a good first test for suspected malignant pleural effusion from breast or lung cancer. They concluded that patients with suspected mesothelioma or pleural thickening are likely to gain little benefit from it.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective cohort study measuring the sensitivity of the first pleural fluid cytology test, with logistic regression to find risk factors for false negative results
• Who was studied: 156 patients with malignant pleural effusion, identified from 607 pleural procedures screened at Christchurch Hospital, Canterbury, New Zealand, 21 July 2017 to 31 October 2019. The mean age was 69.8 years and 88 (56.4%) were female. Lung was the most common cancer site (62) and breast the next most common (23). There were 15 mesotheliomas among 16 primary pleural malignancies.
• Exposure: Not an asbestos exposure study. Asbestos exposure was one of several clinical characteristics recorded: 12 patients (7.7%) had asbestos exposure, 110 (70.5%) had none and 34 (21.8%) had none recorded. No fiber types or doses were given. The main factors studied were the features of the fluid, the CT scan and the cancer that might affect whether cytology detected the cancer.
• Main results:
  • Overall, the first pleural fluid cytology test was positive in 117 of 156 patients with malignant pleural effusion: sensitivity 75.0% (95% CI 67.4–81.6%).
  • Sensitivity in patients with mesothelioma was 33.3% (5 of 15; 95% CI 11.8–61.6%). This was the lowest of the cancer types reported. For primary pleural cancers as a site it was 31.3% (5 of 16).
  • Sensitivity was 79.0% (49 of 62; 95% CI 66.8–88.3%) for lung cancer, 91.3% (21 of 23; 95% CI 72.0–98.9%) for breast cancer and 89.9% (62 of 69; 95% CI 80.2–95.8%) for adenocarcinoma.
  • In the final multivariate model, pleural thickening on CT was associated with higher odds of false negative cytology (OR 3.3; 95% CI 1.2–9.4).
  • In the final multivariate model, cloudy fluid (OR 0.12; 95% CI 0.03–0.54) and yellow/gold fluid (OR 0.24; 95% CI 0.06–0.96, compared with red fluid) were associated with lower odds of false negative cytology.
  • In patients with recorded asbestos exposure, the bivariate analysis showed higher odds of false negative cytology (OR 3.6; 95% CI 1.1–12.1). In the multivariate model the odds ratio was 2.5 (95% CI 0.65–9.7; P = 0.18), which was not statistically significant. Patients whose asbestos exposure was not recorded had lower odds in both analyses (multivariate OR 0.10; 95% CI 0.01–0.80).
  • Fluid pH, lactate dehydrogenase and polynucleated cell proportion did not influence the sensitivity of cytology.
• The authors' conclusion: The authors concluded that pleural fluid cytology remains a good first diagnostic test when malignant pleural effusion from breast or lung cancer is suspected. They concluded that patients with suspected mesothelioma or pleural thickening on imaging are likely to gain little benefit from it, and that alternatives such as pleural biopsy should be considered.
• Limitations the authors state:
  • Retrospective design. Missing data kept some variables, notably performance status, out of the models.
  • The authors did not assess whether radiographic signs of malignancy outside the pleura affected sensitivity.
  • Including multidisciplinary meeting consensus in the definition of malignant pleural effusion could have introduced bias.
  • 18 patients thought by clinicians to have malignant effusion, but without formal multidisciplinary discussion, did not meet the case criteria. The authors state this negatively influenced the sensitivity estimates.
  • The study had limited power for uncommon cancer types and for less common risk factors.
  • Confidence intervals around the estimated effects were broad, so the authors called for confirmation by other studies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Fluid Cytology, Pleural Effusion, Cohort Study, Cytology, Histology, confidence interval, Lung Cancer, Mesothelioma.

Related studies

• Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions — M. Miédougé, P. Rouzaud, et al. (1999)
• Diagnostic yield of pleural fluid cytology in malignant effusions: an Australian tertiary centre experience — P. Loveland, M. Christie, et al. (2018)
• Diagnostic value of biochemical ratios in the differential diagnosis of tuberculous and malignant pleural effusions — U. İlhan, Z. Güney, et al. (2026)
• Pleural fluid cell-free DNA integrity index to identify cytologically negative malignant pleural effusions including mesotheliomas — K.B. Sriram, V. Relan, et al. (2012)
• The role of cytologic evaluation of pleural fluid in the diagnosis of malignant mesothelioma — A.A. Renshaw, B.R. Dean, et al. (1997)
• Differences in Pleural Fluid Amylase Levels in Patients with Malignant Pleural Effusion Based on Cancer Type, Histologic Type, and Epidermal Growth Factor Receptor Mutations — M. Shimoda, Y. Tanaka, et al. (2023)

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