Ancillary Diagnostic Investigations in Malignant Pleural Mesothelioma

Our plain-English summary of Ancillary Diagnostic Investigations in Malignant Pleural Mesothelioma, by A. Dipper, N. Maskell, A. Bibby (Cancers, 2021).

The study

• Authors: A. Dipper, N. Maskell, A. Bibby
• Journal: Cancers
• Published: 2021;13(13)
• Type of article: Review
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

For a number of patients presenting with an undiagnosed pleural effusion, frailty, medical co-morbidity or personal choice may preclude the use of pleural biopsy, the gold standard investigation for diagnosis of malignant pleural mesothelioma (MPM). In this review article, we outline the most recent evidence on ancillary diagnostic tests which may be used to support a diagnosis of MPM where histological samples cannot be obtained or where results are non-diagnostic. Immunocytochemical markers, molecular techniques, diagnostic biomarkers and imaging techniques are discussed. No adjunctive test has a sensitivity and specificity profile to support use in isolation; however, correlation of pleural fluid cytology with relevant radiology and supplementary biomarkers can enable an MDT-consensus clinico-radiological-cytological diagnosis to be made where further invasive tests are not possible or not appropriate. Diagnostic challenges surrounding non-epithelioid MPM are recognised, and there is a critical need for reliable and non-invasive investigative tools in this population.

In plain English

This article was a review, not a new study of patients. The authors summarised published evidence on tests that can support a diagnosis of malignant pleural mesothelioma when pleural biopsy is not possible or inconclusive. They covered tests on cells in pleural fluid, molecular tests, biomarkers and scans. Cited evidence showed that pleural fluid cytology alone had a sensitivity (the share of cases a test detects) of 16% to 73%. A cited meta-analysis found that loss of the BAP1 protein had a pooled sensitivity of 0.56 (95% confidence interval 0.50 to 0.62) and a specificity of 1.00 (0.95 to 1.00) for malignant mesothelioma. In another cited study, combining p16 testing with BAP1 testing raised sensitivity to 0.76 (95% confidence interval 0.62 to 0.88). A cited meta-analysis of serum mesothelin reported a pooled sensitivity of 0.61 and a specificity of 0.87. The authors concluded that no single additional test was accurate enough to use alone. They added that combining fluid cytology, imaging and biomarkers could let a specialist team reach a consensus diagnosis. They noted a critical need for better non-invasive tests for non-epithelioid 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: narrative review of published evidence on ancillary (supporting) diagnostic tests; no new patient data
• Who was studied: No study population of its own. The review focused on patients with suspected malignant pleural mesothelioma for whom frailty, other illness or personal choice rules out pleural biopsy, or whose biopsy results are non-diagnostic.
• Exposure: Not applicable. The review concerned diagnostic tests (pleural fluid cytology, immunocytochemistry, BAP1 and p16 testing, mesothelin, osteopontin, fibulin-3, CT, PET-CT, MRI), not asbestos exposure.
• Main results:
  • Cited evidence: in patients with malignant pleural mesothelioma, the sensitivity of conventional pleural fluid cytology alone ranged from 16% to 73%.
  • A cited meta-analysis (12 studies, 1824 patients, 1016 with mesothelioma) found that BAP1 loss had a pooled sensitivity of 0.56 (95% CI: 0.50–0.62) and a specificity of 1.00 (95% CI: 0.95–1.00) for malignant mesothelioma.
  • In one cited study, combining p16 loss testing with immunohistochemistry for BAP1 loss gave a combined sensitivity of 0.76 (95% CI: 0.62–0.88).
  • A cited 2014 meta-analysis of serum mesothelin (28 publications, 7550 patients) found a pooled sensitivity of 0.61 and a specificity of 0.87 for malignant pleural mesothelioma.
  • A cited meta-analysis of 11 PET-CT studies reported a pooled sensitivity of 95% (95% CI: 92–97%) and a specificity of 82% (95% CI: 76–88%) for telling malignant from benign pleural disease.
  • Cited evidence: 35–46% of patients with pleural malignancy have a CT report read as 'benign' in routine practice.
• The authors' conclusion: The authors concluded that no supporting test is accurate enough to be used on its own. They also concluded that combining pleural fluid cytology with radiology and biomarkers can allow a multidisciplinary team to reach a consensus diagnosis where further invasive tests are not possible or not appropriate.
• Limitations the authors state:
  • The authors noted that studies of BAP1 loss in cytology specimens had been hindered by retrospective design and small sample size. This is a limitation of the evidence reviewed, not one the authors stated for their own review.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Pleural Effusion, Pleural Biopsy, Biomarker, Fluid Cytology, Non-epithelioid.

Related studies

• Retrospective investigation on diagnostic process for benign asbestos pleural effusion (BAPE) using checklist — T. Kishimoto, N. Fujimoto, et al. (2020)
• Ancillary studies in pleural, pericardial, and peritoneal effusion cytology — K.E. Sundling, E.S. Cibas (2018)
• 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 utility of ancillary techniques in effusion cytology — K.V. Nance, J.F. Silverman (1992)
• Automated ancillary cancer history classification for mesothelioma patients from free-text clinical reports — R.A. Wilson, W.W. Chapman, et al. (2010)
• Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment — A.C. Bibby, S. Tsim, et al. (2016)

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