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

Diagnostic Cytopathology 2026 May 20 [Link]

Suzanne M Selvaggi

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.