Our study estimates the sensitivity of pleural fluid cytology in patients with confirmed pleural malignancy, and evaluates whether clinical and fluid characteristics may help clinicians identify patients at risk for false negative cytology results. We found a sensitivity of 75.0% of pleural fluid cytology in all patients with MPE. Pleural fluid cytology sensitivity was most strongly influenced by cancer site and type, with highest sensitivity estimates in patients with adenocarcinoma of breast or lung origin and least sensitive in those with mesothelioma. This sensitivity in our centre was higher than in recent studies although the variation according to cancer type is consistent with the existing literature with the lowest sensitivity in patients with mesothelioma (3–5, 7). In addition, cloudy fluid, potentially indicative of heavily cellular fluid, increased test sensitivity.
Sensitivity of pleural fluid varied by cancer site and histologic type, in keeping with existing literature (3–5, 7), and was higher in patients with lung and breast cancer than in those with mesothelioma. This may reflect that adenocarcinoma of the breast and other sites, may desquamate easily in the pleural cavity (4). The variability in sensitivity by cancer type may explain some of the variability in estimates of the sensitivity of pleural fluid cytology in our study compared to existing literature: the sensitivity from our study broadly matches a recent study from a tertiary Australian hospital where the distribution of malignancy subtypes was similar (3). In contrast a large prospective study from the UK estimated the sensitivity of pleural fluid at substantially lower at 46% (95% CI 42–58%) (5). Notable, in the UK study 16% of their cohort were diagnosed with mesothelioma; the sensitivity of diagnosing a mesothelioma was only 6.1% (2.8–11.2%). Their estimates for patients with adenocarcinoma of the lung, or breast were similar to our own.
For clinicians investigating undifferentiated pleural effusion, features which increase the likelihood of a positive results will be helpful to know, particularly, when faced with negative results. Our study agrees with existing literature that understanding the likely primary malignancy can greatly aid interpretation, for example, in patients suspected to suffer a mesothelioma, a negative cytology result should not be reassuring. In addition, we found that cloudy fluid, potentially indicative of heavily cellular fluid, increased test sensitivity. Other fluid characteristics such as the pH, lactate dehydrogenase and the predominant inflammatory cell type did not influence test sensitivity and were not indicative for clinicians.
In our study just over half of the samples collected had a volume greater than 50 ml. Although our findings were not in concordance, current protocols recommend sampling more than 50 ml of fluid for cytology as previous research shown that samples of > 50 ml have optimal sensitivity (8–10). It may be that improvement in overall sensitivity could be obtained with stricter adherence to pleural fluid volume recommendations. It also serves as a reminder of the importance of regular audit of pleural procedures to ensure an adequate sample volume.
Strengths of our study are that we have included a comprehensive data-set from the only pleural service operating within the study area and that a nationally linked hospital identifying number allowed follow-up was completed on all patients. Our study has retrospective study limitations that influence interpretation. Missing data precluded some variables, notably performance status and pleural thickening on computed tomography scan from inclusion in modelling. Potential bias in the study could also have arisen from the inclusion of multi-disciplinary consensus within the definition for MPE. However, we considered it necessary as many patients with widely disseminated malignancy may not have repeated procedures to confirm the presence of malignant cells in the pleural space due to frailty or lack of benefit. Our sensitivity estimates were negatively influenced by 18 patients for whom clinicians postulated MPE as the cause of the effusion without a formal multidisciplinary discussion and therefore did not meet our case criteria. Finally, our sample size was determined to adequately assess the overall sensitivity of cytology, and our study had limited power to assess sensitivity of pleural fluid cytology in uncommon cancer types, and to identify less common risk factors for false negative cytology.
The main implication of our study for clinical practice is that in patients with suspected MPE due to breast or lung origin, pleural fluid cytology remains a good first diagnostic test. Patients with a suspected mesothelioma are likely gain little benefit from pleural fluid cytology and alternative methods of initial diagnosis such as pleural biopsy should be considered (11–13). Further research is needed into an optimal diagnostic pathway for mesothelioma.