State-of-the-art cytology of pleural fluid, focusing on the diagnosis of mesothelioma

Our plain-English summary of State-of-the-art cytology of pleural fluid, focusing on the diagnosis of mesothelioma, by S.E. Monaco, L. Brcic, S. Dacic (Cytopathology, 2022).

The study

• Authors: S.E. Monaco, L. Brcic, S. Dacic
• Journal: Cytopathology
• Published: 2022;33(1):57-64
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma has always been a challenging diagnosis to render in body cavity cytology samples. This review is a timely update on pleural fluid cytology and ancillary studies that should be considered in the diagnosis of mesothelial proliferations, specifically mesotheliomas. Information about new diagnostic approaches and ancillary studies in mesothelioma was obtained from the peer-reviewed literature and the authors' experiences. Although the morphological diagnosis of mesothelioma is fraught with numerous challenges given the overlap with other diagnostic entities, there are a variety of immunohistochemical and fluorescence in situ hybridization studies available to help in determining mesothelial origin and in distinguishing malignant proliferations from the more common benign or reactive mesothelial proliferations. Although ancillary studies can be helpful, there are important pitfalls to be aware of when interpreting these cases, and this review highlights some of the challenges that require caution.

© 2021 John Wiley & Sons Ltd.

In plain English

This article was a review, not a new study. Drawing on published research, the authors described how mesothelioma is diagnosed from pleural fluid (fluid around the lungs) and which added laboratory tests help. They noted that only mesotheliomas with some epithelioid component can be diagnosed in fluid, because the spindle cells of sarcomatoid mesothelioma rarely shed into it. The review reported that many earlier studies found that loss of BAP1 protein and/or homozygous deletion of the CDKN2A gene in fluid specimens had 100% specificity for separating benign from malignant mesothelial growths. MTAP staining was described as a possible stand-in for CDKN2A testing. p16 staining was not recommended. The authors' group had earlier shown that BAP1 staining and FISH testing for CDKN2A deletion in fluid specimens could give an earlier diagnosis even when the cells looked negative. Where only some cells lost BAP1 and the other tests were normal, the authors' opinion was to report 'suspicious for malignancy' and recommend tissue sampling. The authors concluded that laboratories should use cell blocks with validated staining and FISH tests. Asbestos appeared only in the WHO definition of mesothelioma in situ.

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 diagnostic methods (cytology, immunohistochemistry, FISH) for mesothelioma in pleural fluid
• Who was studied: No patients or samples were studied. The review drew on published peer-reviewed literature, and no datasets were generated or analysed.
• Exposure: Not an exposure study; the review concerns diagnostic tests. Asbestos is mentioned only in the WHO definition of mesothelioma in situ, which refers to patients with recurrent pleural effusions in the setting of heavy asbestos exposure, among other settings.
• Main results:
  • Only mesotheliomas with at least some epithelioid component can be diagnosed in effusions. Spindle cells of sarcomatoid mesothelioma rarely shed into body cavity fluids and typically give false negative diagnoses.
  • The review reported that many earlier studies found that loss of BAP1 expression and/or homozygous deletion of CDKN2A in cytology effusion specimens had 100% specificity in separating benign from malignant mesothelial proliferations.
  • Recent publications suggest that immunohistochemistry for MTAP loss can be used as a surrogate marker for CDKN2A homozygous deletion.
  • Prior studies of p16 immunohistochemistry showed low specificity and sensitivity for detecting mesotheliomas with CDKN2A deletion, and it is not recommended as a surrogate marker.
  • The authors' group previously showed that BAP1 immunohistochemistry and FISH for CDKN2A deletion in effusion specimens can establish the diagnosis earlier, even in cases interpreted as negative by morphology.
  • In the authors' opinion, cases where only a subset of cells lose BAP1, and where FISH shows no homozygous deletion or MTAP is intact, should be diagnosed as 'suspicious for malignancy', with surgical tissue sampling recommended.
  • Agreement in grading of epithelioid mesothelioma between effusion cytology and corresponding surgical specimens is unknown.
• The authors' conclusion: The authors concluded that, because ancillary studies are important for a definitive diagnosis, cytopathology laboratories should use cell block preparations with appropriately validated immunohistochemical and FISH studies, including BAP1 immunostaining, to get the most diagnostic information from pleural fluid samples.

Topics

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

Medical terms in this study, explained in our Lexicon: Cytology, Mesothelioma, Fluid Cytology, Fluorescence In Situ Hybridization (FISH).

Related studies

• Differential Diagnosis of Malignant Pleural Mesothelioma on Cytology: A Gene Expression Panel versus BRCA1-Associated Protein 1 and p16 Tests — R. Bruno, G. Alì, et al. (2020)
• Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens — K.B. Berg, A.M. Churg, et al. (2020)
• Pre-operative diagnosis of malignant mesothelioma of tunica vaginalis testis by hydrocele fluid cytology — S.C. Gupta, A.K. Gupta, et al. (1998)
• 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)
• Proceedings of the American Society of Cytopathology companion session at the 2019 United States and Canadian Academy of Pathology Annual meeting, part 2: effusion cytology with focus on theranostics and diagnosis of malignant mesothelioma — M.T. Siddiqui, F. Schmitt, et al. (2019)
• Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers — D.W. Henderson, G. Reid, et al. (2013)

Browse more research in Cytopathology, or return to medical research.