Investigating unilateral pleural effusions: the role of cytology

Our plain-English summary of Investigating unilateral pleural effusions: the role of cytology, by D.T. Arnold, D. De Fonseka, S. Perry, et al (The European Respiratory Journal, 2018).

The study

• Authors: D.T. Arnold, D. De Fonseka, S. Perry, A. Morley, J.E. Harvey, A. Medford, M. Brett, N.A. Maskell
• Journal: The European Respiratory Journal
• Published: 2018;52(5)
• Cited by: 145 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The vast majority of undiagnosed unilateral pleural effusions have fluid sent for cytological analysis. Despite widespread use, there is uncertainty about its sensitivity to diagnose malignant pleural effusions (MPEs). Our aim was to ascertain the utility of cytology using a large prospective cohort.Consecutive patients presenting with an undiagnosed unilateral pleural effusion were recruited to this UK-based study. All had pleural fluid sent for cytological analysis. Cytological sensitivity was based on the final diagnosis at 12 months, confirmed by two consultants.Over 8 years, 921 patients were recruited, of which 515 had a MPE. Overall sensitivity of fluid cytology to diagnose malignancy was 46% (95% CI 42-58%). There was variation in sensitivity depending on cancer primary, with mesothelioma (6%) and haematological malignancies (40%) being significantly lower than adenocarcinomas (79%). MPEs secondary to ovarian cancer had high pick-up rates (95%). In asbestos-exposed males with exudative effusions, the risk of MPE was 60%, but cytological sensitivity was 11%.This is the largest prospective study of pleural fluid cytology and informs discussions with patients about the likely requirement for investigations following thoracentesis. In patients presenting with a clinical suspicion of mesothelioma, cytological sensitivity is low, so more definitive investigations could be performed sooner.

Copyright ©ERS 2018.

In plain English

This prospective observational study at a single pleural service in Bristol, UK, followed 921 consecutive patients with an unexplained fluid build-up around one lung (a unilateral pleural effusion). They were recruited between December 2008 and December 2016. All had the fluid examined for cancer cells (cytology). Patients were followed for up to 12 months or until death, and two consultants agreed each final diagnosis. In all, 515 patients had a malignant effusion. Overall, cytology detected 46% (95% CI 42-58) of malignant effusions. Detection was close to 95% for ovarian cancer but 6% for mesothelioma, where 94% of patients needed a biopsy before diagnosis. In asbestos-exposed men with an exudative effusion and no history of cancer, sensitivity fell to 11% (CI 6-17), although over 60% of this group had a malignant effusion. The authors concluded that for these men, arranging further tests without waiting for the cytology result is justifiable. They noted that the study was carried out at a single centre and that the cytopathologists were not blinded to the patients' clinical information.

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: Prospective observational study at a single centre. All patients were followed up to 12 months or until death, whichever came first, and were assigned a final diagnosis. The final diagnosis was agreed by two independent consultant respiratory physicians.
• Who was studied: 921 consecutive patients with an undiagnosed unilateral pleural effusion, recruited between December 2008 and December 2016 in the UK (Bristol). 515 of them had a malignant pleural effusion.
• Exposure: This is not an asbestos exposure study. The study evaluated pleural fluid cytology as a diagnostic test. Asbestos exposure was recorded as a patient characteristic and used to define a subgroup. The article does not say how exposure was assessed and does not name fiber types.
• Main results:
  • Among all 515 malignant effusions, the overall sensitivity of fluid cytology for malignancy was 46% (95% CI 42-58).
  • Sensitivity was significantly lower for mesothelioma (6%) and haematological malignancies (40%) than for adenocarcinomas (79%).
  • In mesothelioma, 94% of patients needed a definitive biopsy before a diagnosis could be made.
  • In ovarian cancer, sensitivity approached 95%, significantly higher than in other adenocarcinomas (p=0.013).
  • In asbestos-exposed men with exudative effusions, the risk of a malignant pleural effusion was 60% but cytological sensitivity was 11%.
  • Within exudative effusions, the flow chart gives a subgroup of asbestos-exposed male patients without a history of cancer (n=210). In this subgroup, cytology sensitivity was 11% (C.I. 6-17). This was significantly lower than in other groups (p less than 0.01), although the risk of malignancy in this subgroup was over 60% (62.9% in the flow chart).
  • In that asbestos-exposed male subgroup, 117 of 132 patients with malignancy had a 'suspicion of malignancy' on their initial CT scan.
  • The risk of malignancy was 15% (21/118) in transudative effusions and 62% (495/803) in exudative effusions.
  • Among malignant effusions where the first cytology was non-diagnostic, cytology was repeated in 106 cases. Six of these repeat samples were diagnostic (5.6%).
  • The authors attributed the overall sensitivity mainly to the high proportion of mesothelioma in their cohort. When they artificially lowered mesothelioma to about 10% of malignant effusions, sensitivity rose to 55%.
• The authors' conclusion: The authors concluded that haematological malignancy and mesothelioma were unlikely to be diagnosed by pleural fluid cytology alone. They also concluded that in asbestos-exposed men with an exudative effusion and no history of cancer, organising further tests without waiting for the cytology result is justifiable.
• Limitations the authors state:
  • The study was carried out at a single centre.
  • The cytopathologists were not blinded to clinical information, which may have influenced how they read the specimens.
  • Testing practice changed over the 8-year recruitment period, so how often fluid samples were suitable for further analysis is difficult to quantify.
  • Patient numbers for rarer cancer sites were small.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Cytology, Fluid Cytology, Mesothelioma, Adenocarcinoma, Ovarian Cancer, Thoracentesis.

Related studies

• Diagnostic yield of pleural fluid cytology in malignant effusions: an Australian tertiary centre experience — P. Loveland, M. Christie, et al. (2018)
• The diagnostic utility of D2-40, calretinin, CK5/6, desmin and MOC-31 in the differentiation of mesothelioma from adenocarcinoma in pleural effusion cytology — T.S. Hyun, M. Barnes, et al. (2012)
• Small orangiophilic squamous-like cells: an underrecognized and useful morphological feature for the diagnosis of malignant mesothelioma in pleural effusion cytology — L. Chen, S.G. Caldero, et al. (2014)
• Claudin-4 immunohistochemistry is highly effective in distinguishing adenocarcinoma from malignant mesothelioma in effusion cytology — V.Y. Jo, E.S. Cibas, et al. (2014)
• Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma — H. Domínguez-Malagón, A.M. Cano-Valdez, et al. (2016)
• EZH2, a unique marker of malignancy in effusion cytology — H. Jiang, R. Gupta, et al. (2014)

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