Diagnostic sensitivity of pleural fluid cytology in malignant pleural effusions: systematic review and meta-analysis

Abstract

BackgroundPleural fluid cytology is an important diagnostic test used for the investigation of pleural effusions. There is considerable variability in the reported sensitivity for the diagnosis of malignant pleural effusions (MPE) in the literature.ObjectiveThe purpose of this review is to determine the diagnostic sensitivity of pleural fluid cytology for MPE, both overall and by tumour type, to better inform the decision-making process when investigating pleural effusions.Data sourcesA literature search of EMBASE and MEDLINE was performed by four reviewers. Articles satisfying inclusion criteria were evaluated for bias using the QUADAS-2 tool.Data extractionFor quantitative analysis, we performed a metaanalysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on primary cancer site and meta-regression by year of publication.SynthesisThirty-six studies with 6057 patients with MPE were included in the meta-analysis. The overall diagnostic sensitivity of pleural fluid cytology for MPE was 58.2% (95% CI 52.5% to 63.9%; range 20.5%–86.0%). There was substantial heterogeneity present among studies (I2 95.5%). For primary thoracic malignancies, sensitivity was highest in lung adenocarcinoma (83.6%; 95% CI 77.7% to 89.6%) and lowest in lung squamous cell carcinoma (24.2%; 95% CI 17.0% to 31.5%) and mesothelioma (28.9%; 95% CI 16.2% to 41.5%). For malignancies with extrathoracic origin, sensitivity was high for ovarian cancer (85.2%; 95% CI 74.2% to 96.1%) and modest for breast cancer (65.3%; 95% CI 49.8% to 80.8%).ConclusionsPleural fluid cytology has an overall sensitivity of 58.2% for the diagnosis of MPE. Clinicians should be aware of the high variability in diagnostic sensitivity by primary tumour type as well as the potential reasons for false-negative cytology results.PROSPERO registration numberCRD42021231473.

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“…Cytology has the advantages of low cost, rapidity, and high specificity, but its sensitivity is only 60% and its diagnostic accuracy is observer‐dependent. 7 , 8 , 9 Pleural biopsy and thoracoscopy have high accuracy, but they are invasive tools and can cause complications such as infection and bleeding. In addition, special training is needed for thoracoscopy, limiting its use in remote areas.…”

“…However, these diagnostic tools have limitations. Cytology has the advantages of low cost, rapidity, and high specificity, but its sensitivity is only 60% and its diagnostic accuracy is observer‐dependent 7–9 . Pleural biopsy and thoracoscopy have high accuracy, but they are invasive tools and can cause complications such as infection and bleeding.…”

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“…Malignancy in the pleural space often presents with a pleural effusion, and the first diagnostic step is to obtain pleural fluid cytology [ 10 ]. However, a positive cytological result is more likely in certain type of cancers (with breast and ovarian cancers being most likely to provide positive pleural fluid cytology) than others such as malignant pleural mesothelioma (MPM) [ 11 , 12 , 13 ]. In MPM, pleural fluid cytology typically has a low diagnostic yield of 6–32%, and parietal pleura is often required for full characterisation of the tumour [ 11 , 12 , 13 ].…”

“…However, a positive cytological result is more likely in certain type of cancers (with breast and ovarian cancers being most likely to provide positive pleural fluid cytology) than others such as malignant pleural mesothelioma (MPM) [ 11 , 12 , 13 ]. In MPM, pleural fluid cytology typically has a low diagnostic yield of 6–32%, and parietal pleura is often required for full characterisation of the tumour [ 11 , 12 , 13 ]. There is compelling evidence that if the probability of MPM is high, according to clinical and radiological features, a direct to LAT approach should be adopted [ 14 ].…”

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“…Clinical discrimination of PE types is crucial and the gold standard method for MPE detection is cytology of the PE or histology of the pleural membrane by closed biopsy or by thoracoscopy, the latter being more invasive. Although pleural fluid cytology has high specificity, the sensitivity is moderate, 58.2% (95% CI 52.5% to 63.9%) [ 5 ]. An imprecise diagnosis makes the discrimination of disease stages more difficult, and it is an obstacle to defining a therapeutic strategy [ 6 ].…”