The Diagnostic Value of Immunohistochemistry and Biomarkers in the Diagnosis of Mesothelioma in Pleural/Peritoneal Effusions

Our plain-English summary of The Diagnostic Value of Immunohistochemistry and Biomarkers in the Diagnosis of Mesothelioma in Pleural/Peritoneal Effusions, by S.M. Selvaggi (Diagnostic Cytopathology, 2026).

The study

• Author: S.M. Selvaggi
• Journal: Diagnostic Cytopathology
• Published: 2026;54(9):631-636
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Mesothelioma is a rare tumor that arises from the serosal cells lining the serous cavities, most commonly the pleura followed by the peritoneum. Presenting symptoms include pleuritic pain and bloody effusions that recur. Although cytologic analysis cannot determine the mesothelial subtype or in situ from invasive disease, the application of biomarkers to serous effusions has aided in distinguishing benign from malignant mesothelial cells. This study evaluates the diagnostic value of specialized techniques in the cytologic diagnosis of mesothelioma pre- and post-implementation of biomarkers and a robust immunohistochemical (IHC) panel.

Methods: From January 1, 2013, through December 31, 2025, 26 effusions (20 pleural, six peritoneal) from 16 males and four females (mean, 72 years; median, 75 years) were evaluated and contained atypical mesothelial cells. In each case, ThinPrep slides were made for cytologic analysis and cell blocks were prepared for IHC and biomarker evaluation. Prior to 2017, the IHC markers were limited, whereas after that time, biomarkers including BAP1 and MTAP were available.

Results: Cytologically the effusions were cellular and contained atypical, enlarged mesothelial cells arranged singly and in clusters with a normal nuclear/cytoplasmic ratio. Five effusions (2013-2015) were diagnosed as suspicious for mesothelioma based on the cytologic findings and a limited IHC panel (calretinin, CK 5/6, TTF-1). The diagnosis was confirmed on biopsy/resection specimens. For 17 effusions (2017-2025), an expanded IHC and biomarker panel aided in the cytologic diagnosis of mesothelioma. Three effusions were from patients with a known history of pulmonary mesothelioma, so IHC stains were not performed. Histologic confirmation was done in 23 cases.

Conclusions: The application of IHC and biomarkers in combination with cytomorphology aids in the diagnosis of mesothelioma on fluid cytology.

© 2026 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.

In plain English

This study described 26 fluid samples (20 pleural, six peritoneal) from 16 men and four women aged 52 to 92. The University of Wisconsin Hospital cytopathology laboratory processed them between 2013 and 2025; each contained abnormal-looking mesothelial cells. The study examined how lab stains (immunohistochemistry) and the newer markers BAP1 and MTAP helped diagnose mesothelioma from these fluids. It did not report the patients' asbestos exposure histories. From 2013 to 2015, five samples from three patients were called suspicious for mesothelioma using a limited stain panel, and later biopsies or surgery confirmed mesothelioma. From 2017 to 2025, 21 samples from 17 patients were examined. A wider panel supported mesothelioma in 14 cases, and MTAP was also tested in 10 of them. In samples tested for these markers, the abnormal cells showed BAP1 and MTAP loss. Tissue confirmation was done in 23 cases. Because there were few cases, the author did not calculate how accurate the markers were. The author concluded that the stains and markers, combined with how the cells look, aid mesothelioma diagnosis in fluid samples. The article's case counts are not fully consistent.

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: Case series of pleural and peritoneal fluid specimens from a single hospital cytopathology laboratory
• Who was studied: 26 serous fluid specimens (20 pleural, 6 peritoneal) from 16 male and 4 female patients aged 52 to 92 years (mean 72, median 75), University of Wisconsin Hospital, January 2013 through December 2025. All specimens contained atypical mesothelial cells.
• Exposure: Not studied. The article reports no asbestos exposure histories for the study patients. Its introduction mentions only the previously reported link between asbestos and mesothelioma. The study evaluates diagnostic stains (calretinin, CK 5/6, WT-1, BAP1, MTAP, claudin 4, TTF-1) on fluid specimens.
• Main results:
  • 2013 to 2015: five effusions from three patients (three pleural, two peritoneal) were diagnosed as suspicious for mesothelioma. The limited stain panel was positive for calretinin and CK 5/6 and negative for TTF-1. Later biopsies or resections confirmed mesothelioma (epithelioid, per the table).
  • 2017 to 2025: 21 effusions from 17 patients were examined. The expanded panel supported a diagnosis of mesothelioma in 14 cases, and MTAP was also tested in 10 of these.
  • In samples tested with these markers, the atypical mesothelial cells were strongly positive for CK 5/6 and calretinin and showed loss of BAP1 and MTAP expression. Not every sample was tested: MTAP was done in 10 cases, and some effusions had no immunohistochemical staining.
  • Histologic (tissue) confirmation was done in 23 cases.
• The authors' conclusion: The author concluded that cytology combined with immunohistochemistry and biomarkers aids the diagnosis of mesothelioma in pleural and peritoneal fluids.
• Limitations the authors state:
  • Because of the limited number of cases, sensitivity and specificity of the biomarkers were not calculated.

Topics

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

Medical terms in this study, explained in our Lexicon: Immunohistochemistry, Biomarker, Mesothelioma, Serous Cavities, Pleura, Peritoneum, Pleuritic Chest Pain, Mesothelial Cells.

Related studies

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• Diagnostic and prognostic value of Ki67 proliferation fraction in serous effusions — A. Schönherr, M. Bayer, et al. (2004)
• The diagnostic role of BAP1 in serous effusions — B. Davidson, M. Tötsch, et al. (2018)
• Diagnostic Value of Claudin-4 and EZH2 Immunohistochemistry in Effusion Cytology — A. Elhosainy, M.M.A. Hafez, et al. (2022)
• The importance of EZH2 and MOC-31 expression in the differential diagnosis of benign and malignant effusions — C. Sadullahoglu, D. Nart, et al. (2017)
• 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)

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