Diagnostic utility of BAP1 for malignant pleural mesothelioma in pleural fluid specimens with atypical morphology

Our plain-English summary of Diagnostic utility of BAP1 for malignant pleural mesothelioma in pleural fluid specimens with atypical morphology, by A. Louw, Y.C.G. Lee, N. Acott, et al (Cytopathology, 2022).

The study

• Authors: A. Louw, Y.C.G. Lee, N. Acott, J. Creaney, C. van Vliet, S.M. Chai
• Journal: Cytopathology
• Published: 2022;33(1):84-92
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objective: To assess the utility of BRCA1-associated protein 1 (BAP1) immunohistochemistry (IHC) for the diagnosis of malignant pleural mesothelioma (MPM) in fluid samples with atypical cytology.

Methods: Pleural fluid samples with an atypical mesothelial proliferation (diagnostic categories: 'atypical' and 'suspicious') received between January 2015 and March 2018 at a tertiary referral centre were identified. Results of routine IHC testing were recorded for each case. BAP1 by IHC was performed and a final diagnosis sought from subsequent pathology specimens, medical records, or consensus clinical diagnosis.

Results: Of 50 cases identified, 41 were reported as atypical and 9 as suspicious. Seven (14%) demonstrated loss of BAP1 staining, 40 retained BAP1 staining, 1 had heterogeneous staining, and 2 had insufficient cells for analysis. All seven cases with BAP1 loss were diagnosed with MPM on follow-up. Of those with retained BAP1, 52.5% (21) were subsequently diagnosed with MPM, while 40% (16) had non-MPM diagnoses after a median follow-up of 24 months. Three cases were not further investigated based on patient and clinician decision. The case with heterogeneous staining was diagnosed as mesothelioma by clinical consensus.

Conclusions: BAP1 IHC loss is highly specific for malignancy and has value as a rule-in test. Even in a tertiary centre with clinical interest in the cytological diagnosis of MPM this investigation was able to increase diagnostic accuracy beyond routine IHC studies. Cytological criteria remain valuable, as retained BAP1 in an atypical or suspicious mesothelial proliferation cannot exclude malignancy.

© 2021 John Wiley & Sons Ltd.

In plain English

This retrospective study was carried out at a tertiary referral centre for pleural disease in Western Australia. It asked whether a laboratory stain for the protein BAP1 helps diagnose malignant pleural mesothelioma in pleural fluid samples whose cells looked abnormal but not clearly cancerous (reported as 'atypical' or 'suspicious'). The authors identified 50 such samples received between January 2015 and March 2018 and then looked up each patient's later diagnosis. Seven samples showed loss of BAP1 staining, and all seven patients were later diagnosed with mesothelioma. Forty samples kept BAP1 staining. Of these, 21 (52.5%) were later diagnosed with mesothelioma and 16 (40%) had fluid caused by other conditions such as cardiac failure. None of the effusions found to have other causes showed BAP1 loss. Overall, BAP1 loss was present in 7 of the 29 patients (24%) later diagnosed with mesothelioma. The authors concluded that BAP1 loss is valuable as a 'rule-in' test and raised diagnostic accuracy in this group by 14%, but that retained BAP1 cannot rule out mesothelioma. They noted the study was retrospective and small. The study did not assess 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 diagnostic study of pleural fluid specimens, with follow-up of each patient's later diagnosis
• Who was studied: 50 pleural fluid specimens reported as 'atypical' (41) or 'suspicious' (9) mesothelial proliferations, received at a tertiary referral centre in Western Australia between January 2015 and March 2018, selected from 2091 pleural fluid specimens received in that period. 86% of patients were male; average age 72 years (range 30 to 97).
• Exposure: No asbestos exposure was assessed. The study evaluated a laboratory stain, BAP1 immunohistochemistry, performed on cell blocks from the pleural fluid samples.
• Main results:
  • Of the 50 samples, 7 showed loss of BAP1 staining and 40 retained BAP1 staining. 1 showed heterogeneous staining and 2 had too few cells for analysis.
  • All 7 patients whose samples showed BAP1 loss were later diagnosed with malignant pleural mesothelioma, a median of 1.2 months after the first atypical sample.
  • Of the 40 samples that retained BAP1 staining, 21 (52.5%) were later diagnosed with mesothelioma on biopsy or cytology.
  • Of the 40 samples that retained BAP1 staining, 16 patients (40%) had effusions due to other diseases, most commonly cardiac failure. These patients were followed for a median of 24 months. Three patients were not investigated further.
  • No effusion confirmed to be due to another cause showed BAP1 loss.
  • BAP1 loss was found in 7 of the 29 patients (24%) later diagnosed with mesothelioma.
  • Four of the five samples with strong EMA staining came from patients later diagnosed with epithelioid mesothelioma, and all four of these also showed BAP1 loss.
• The authors' conclusion: The authors concluded that BAP1 staining is valuable as a 'rule-in' test in pleural fluid samples with atypical cells and increased diagnostic accuracy in this group by 14%. They also concluded that retained BAP1 staining did not exclude mesothelioma, so assessment of the cells' appearance remains important.
• Limitations the authors state:
  • The study was retrospective and included a small number of cases.
  • The authors said the results need evaluation in larger groups and more varied clinical settings.
  • Interpreting the cases involves some subjectivity.
  • The other stains performed varied from case to case, depending on the reporting pathologist.
  • As a tertiary centre with a dedicated pleural service, the site probably had patients more likely to have mesothelioma than other centres.

Topics

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

Medical terms in this study, explained in our Lexicon: BAP1, Pleural Mesothelioma, Immunohistochemistry, Cytology, Atypical Mesothelial Proliferation, Pathology, Mesothelioma.

Related studies

• Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens — H.C. Hwang, B.S. Sheffield, et al. (2016)
• Utility of BRCA1-associated protein 1 immunoperoxidase stain to differentiate benign versus malignant mesothelial proliferations in cytologic specimens — Z. McCroskey, G. Staerkel, et al. (2017)
• Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma — A. Shinozaki-Ushiku, T. Ushiku, et al. (2017)
• Diagnostic utility of pleural fluid eosinophilia — M. Adelman, S.M. Albelda, et al. (1984)
• Loss of BAP1 Expression in Atypical Mesothelial Proliferations Helps to Predict Malignant Mesothelioma — R. Pillappa, J.J. Maleszewski, et al. (2018)
• Malignant cells from pleural fluids in malignant mesothelioma patients reveal novel mutations — S. Sneddon, I. Dick, et al. (2018)

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