Accuracy and reproducibility of pleural effusion cytology

Our plain-English summary of Accuracy and reproducibility of pleural effusion cytology, by A. Fassina, U. Fedeli, M. Corradin, et al (Legal Medicine, 2008).

The study

• Authors: A. Fassina, U. Fedeli, M. Corradin, M. Da Frè, L. Fabbris
• Journal: Legal Medicine
• Published: 2008;10(1):20-5
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The increasing number of Malignant Mesothelioma (MM) cases that arrive for expert examinations to court for compensation reasons in subjects exposed to asbestos, in many instances rely exclusively on cytological smears of pleural effusion. We evaluated the accuracy and reproducibility of cytological pleural effusions, based on morphological criteria alone. Nine pathologists and eight residents from seven institutions in north-east Italy blindly examined 45 smears of MM (17), metastases (14) and benign effusions (14), in two rounds. Diagnoses had been confirmed by immunohistochemical and clinical follow-up, and eventually at autopsy. Diagnostic accuracy, interobserver and intraobserver agreement in the distinction of benign vs malignant cases, and in the differentiation of primary from metastatic malignancies, were evaluated. The distinction of benign from malignant smears resulted rather satisfactory (k=0.514), but markedly decreased in differentiation of MM from metastases (overall agreement: k=0.343), as well as when readings from residents were analyzed (k=0.132). Cytology is a useful and reliable tool in the identification of malignancies, but when the distinction of primary from metastatic tumors is addressed morphological criteria alone are not sufficient for a definite diagnosis of MM and the use of cell blocks, immunohistochemistry (IHC) and molecular ancillary techniques are recommended.

In plain English

This study tested how accurately and consistently pathologists could diagnose pleural effusion cytology smears, which are slides of fluid from around the lung, using microscopic appearance alone. The authors used 45 archived smears from Monfalcone Hospital in north-eastern Italy. Seventeen were malignant mesothelioma, all in men who worked in a naval dockyards area. Fourteen were metastatic cancers and 14 were benign effusions, with diagnoses confirmed by other methods. Nine pathologists and eight pathology residents read the slides blind, and the pathologists read them again five months later. In telling benign from malignant, the experts' mean sensitivity was 81.2% and mean specificity 81.3%. Their agreement score (kappa, where 1 is complete agreement and 0 is chance) was 0.514. In separating mesothelioma from metastases, expert agreement was poor (kappa 0.343), and individual experts correctly identified mesothelioma in 1 to 11 of the 17 cases. Residents' specificity was 44.6%. The authors concluded that, in court, expert examination based only on effusion smears cannot be considered sufficient for a definite conclusion of mesothelioma.

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: Diagnostic accuracy and reproducibility study: archived cytology slides read blind by multiple observers, with interobserver agreement and, for experts, intraobserver agreement measured
• Who was studied: 45 pleural effusion specimens from the archives of the Pathology Department of Monfalcone Hospital, north-eastern Italy: 17 malignant mesothelioma (all male, aged 62 to 83), 14 metastases and 14 benign effusions (4 of the benign cases had benign pleural plaques at autopsy). The readers were nine pathologists from Cytopathology Units in north-eastern Italy and eight pathology residents.
• Exposure: Asbestos exposure was not measured. The study assessed diagnosis from cytology smears based on morphological criteria alone. The mesothelioma patients worked in a naval dockyards industrial area. No fiber types are named.
• Main results:
  • Expert observers, benign vs malignant: sensitivity ranged from 65.5% to 90.3% (mean 81.2%) and specificity from 64.3% to 100% (mean 81.3%).
  • By majority reading of the reviewers, 10 of 14 benign effusions were correctly identified as benign and 25 of 31 malignant effusions were correctly identified as malignant.
  • Individual expert observers correctly gave the mesothelioma diagnosis in 1 to 11 of the 17 mesothelioma cases, and the metastasis diagnosis in 6 to 10 of the 14 metastasis cases.
  • Residents had a diagnostic accuracy of 71.0% in distinguishing malignant from benign cases.
  • Residents' specificity was 44.6%, because more benign cases were wrongly classified as malignant.
  • Expert interobserver agreement for benign vs malignant: kappa 0.514, with no differences between benign and neoplastic effusions.
  • Expert agreement in distinguishing mesothelioma from metastases was poor (kappa 0.343). It was kappa 0.385 for metastases and 0.192 for mesothelioma.
  • In the resident group, agreement for benign vs malignant was kappa 0.132, as reported in the Results section.
  • Expert intraobserver agreement after five months was described as rather good except for two observers, with Cohen's kappa ranging from 0.31 to 0.70.
• The authors' conclusion: The authors concluded that morphology alone allows a first separation of benign from malignant effusions. They found that distinguishing mesothelioma from metastatic tumors remains doubtful. They stated that, in court, expert examination based exclusively on effusion smears cannot be considered sufficient for a definite conclusion of mesothelioma, and consequently for asbestos exposure compensation.
• Limitations the authors state:
  • The authors note that the lower agreement for the three separate diagnostic categories may be partly explained by Cohen's kappa necessarily tending to be lower when there are more than two categories.

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: Pleural Effusion, Cytology, Malignant Mesothelioma, Autopsy, Cell Block, Immunohistochemistry.

Related studies

• The role of liquid-based cytology and ancillary techniques in pleural and pericardic effusions: an institutional experience — E.D. Rossi, T. Bizzarro, et al. (2015)
• The value of anti-calretinin antibody in the differential diagnosis of normal and reactive mesothelia versus metastatic tumors in effusion cytology — H. Nagel, B. Hemmerlein, et al. (1998)
• Updates in Effusion Cytology — C.M. Lepus, M. Vivero (2018)
• A combination of MTAP and BAP1 immunohistochemistry in pleural effusion cytology for the diagnosis of mesothelioma — Y. Kinoshita, T. Hida, et al. (2018)
• Diagnostic accuracy and safety of semirigid thoracoscopy in exudative pleural effusions in Denmark — F. Willendrup, U. Bodtger, et al. (2014)
• Electron microscopy in the cytological examination of metastatic pleural effusions — M. Legrand, R. Pariente (1976)

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