A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit

Our plain-English summary of A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit, by A. Segal, G.F. Sterrett, F.A. Frost, et al (Pathology, 2013).

The study

• Authors: A. Segal, G.F. Sterrett, F.A. Frost, K.B. Shilkin, N.J. Olsen, A.W. Musk, A.K. Nowak, B.W. Robinson, J. Creaney
• Journal: Pathology
• Published: 2013;45(1):44-8
• Cited by: 83 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aims: Cytological diagnosis of malignant pleural mesothelioma (MPM) is controversial, but has been used in our institution for over 30 years. To assess the role of effusion cytology in mesothelioma diagnosis we conducted an audit of pleural fluid cytology results over a 20 year period (1988-2007).

Methods: Pleural samples were received from 6285 patients; data linkage with Western Australian Cancer and Mesothelioma Registries demonstrated that 815 of these patients had a diagnosis of MPM. Cytological examination of a pleural effusion specimen had been performed in 517 (63%) of these 815 patients.

Results: Definitive cytological diagnosis of MPM was made in 377/517 cases, resulting in an 'absolute' sensitivity of 73%. An additional 66 patients were diagnosed as atypical/suspicious, resulting in a 'complete' sensitivity of 86%. If only biopsy/necropsy proven cases are considered, the absolute sensitivity is 68% and the complete sensitivity is 82%. There were no false positive diagnoses of malignancy; two patients with metastatic adenocarcinoma were initially diagnosed as MPM, prior to the availability of specific mesothelial markers, resulting in a positive predictive value of 99%.

Conclusions: Effusion cytology is an inexpensive, minimally invasive procedure which should be included in the diagnostic work-up of cases of suspected MPM.

In plain English

This retrospective audit covered pleural samples from 6285 patients at the PathWest QEII laboratory in Perth, Western Australia, from 1988 to 2007. Linking records with the Western Australian Cancer and Mesothelioma Registries identified 815 patients with confirmed malignant pleural mesothelioma (MPM). Of these, 517 had had pleural fluid (effusion) cytology. Cytology gave a definite MPM diagnosis in 377 of 517, an 'absolute' sensitivity of 73%. Counting 66 more reported as atypical or suspicious, the 'complete' sensitivity was 86%. Among the 277 biopsy- or necropsy-confirmed patients who also had cytology, the figures were 68% and 82%. All 379 cytology diagnoses of MPM were malignant, but two were metastatic breast and kidney cancers, a positive predictive value of 99% for MPM. Of the 140 mesothelioma cases without a definitive cytology diagnosis, 45 (32%) were sarcomatoid on biopsy. The authors noted that case finding depended on correct database coding and that delays between samples could bias results against cytology. They concluded that effusion cytology should be included in the diagnostic work-up of suspected MPM. The study did not examine asbestos exposure.

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 audit of laboratory pathology records (1988–2007), with data linkage to the Western Australian Cancer Registry and Mesothelioma Registry; a diagnostic accuracy study, not a prospective study
• Who was studied: 6285 patients (2620 female) with pleural samples at PathWest QEII laboratory, Perth, Western Australia, 1988–2007. Of these, 5237 had pleural effusion specimens. 815 had confirmed malignant pleural mesothelioma (127 female, mean age 66.5 years), and 517 of these had effusion cytology.
• Exposure: Not an exposure study: what was evaluated was pleural effusion cytology as a test for diagnosing malignant pleural mesothelioma. The article gives no data on asbestos fiber types, products, jobs or doses.
• Main results:
  • Among the 517 patients with confirmed MPM who had effusion cytology, 377 had a definitive cytological diagnosis of MPM, an absolute sensitivity of 73%.
  • Of the 140 confirmed MPM patients without a definitive cytological diagnosis, 66 had at least one specimen reported as atypical or suspicious, giving a complete sensitivity of 86%.
  • Of the 518 patients whose MPM was confirmed by biopsy and/or necropsy, 277 (53%) had effusion cytology. Among these 277, absolute sensitivity was 68% (188 definitive diagnoses) and complete sensitivity was 82% (38 further atypical or suspicious).
  • All 379 cases diagnosed as MPM by effusion cytology proved to be malignant. Two were wrongly classed as MPM: one was metastatic breast carcinoma and one metastatic renal cell carcinoma. This gave a positive predictive value of 99% for a diagnosis of MPM.
  • Specificity was reported as 99.9%, with 'not MPM' defined as absence from the Mesothelioma Registry. The negative predictive value was 97%.
  • Of the 140 confirmed MPM cases without a definitive cytological diagnosis of MPM (a group that includes the 66 reported as atypical or suspicious), 45 (32%) had sarcomatoid histology on biopsy.
  • On average, the positive cytology sample came 29 days before the histological or electron microscopy diagnosis. In one case, the cytological diagnosis came 14 years before the patient presented with metastatic MPM.
• The authors' conclusion: The authors concluded that effusion cytology is an inexpensive, minimally invasive procedure that should be included in the diagnostic work-up of suspected MPM. In their opinion, a definitive cytological diagnosis should be considered sufficient for management decisions, including clinical trial eligibility and medico-legal compensation.
• Limitations the authors state:
  • It could not be confirmed that all MPM cases were found, because case collection depended on correct database coding. The authors state that registry linkage should have detected missed cases.
  • Complex diagnostic pathways made statistical evaluation of accuracy difficult. For patients with multiple samples, the 'worst' diagnosis was used.
  • Time lapses between a cytology sample and the final histological diagnosis could create apparent false negatives, biasing results against cytology.
  • Because this was an audit, diagnostic protocols changed over the 20 years. Positive mesothelial markers were not in use for most of the period.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Cytology, Mesothelioma, Fluid Cytology, Pleural Effusion, Biopsy, Autopsy, Adenocarcinoma.

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• The diagnosis of malignant mesothelioma in effusion cytology: a reappraisal and results of a multi-institution survey — A. Paintal, K. Raparia, et al. (2013)
• Young investigator challenge: MicroRNA-21/MicroRNA-126 profiling as a novel tool for the diagnosis of malignant mesothelioma in pleural effusion cytology — R. Cappellesso, L. Nicolè, et al. (2016)
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