Cytopathology in focus: Advances in detection of mesothelioma in cytology pleural fluid specimens

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The article by Louw, et al.,² explores the boundaries of mesothelioma in situ within pleural effusion samples and any implications for cytologic evaluation. The authors detected abnormalities of BAP1 immunohistochemistry and/or CDKN2A FISH in patients with pleural mesothelioma who in their initial specimen (at least two years prior) did not meet the diagnostic criteria for pleural mesothelioma. Despite the limitations of the study (retrospective design, small cohort, paucity of cells, archived cell blocks), their study highlights the possibility of a cytological diagnosis of early mesothelioma/equivalent for mesothelioma in situ in the correct clinical setting.

FISH, fluorescence in situ hybridization; IHC, immunohistochemistry.
Monaco SE, Brcic L, Dacic S. State-of-the-art cytology of pleural fluid, focusing on the diagnosis of mesothelioma. Cytopath. 2022;33:57–64. https://doi.org/10.1111/cyt.13055. (Adapted from: Beasley MB, et al. Virchows Arch. 2021;478[1]:59–72.)

The last article, by Girolami, et al.,³ is a systematic literature review that evaluates multiple biomarkers for sensitivity and specificity. BAP1 loss by immunohistochemistry carries very high specificity (99 percent) but a sensitivity of only 65 percent; CDKN2A deletion and MTAP loss also each have high specificity but even lower sensitivity. The use of both CDKN2A deletion and BAP1 loss immunohistochemistry provides a higher sensitivity of 83 percent and maximal 100 percent specificity. The importance of internal positive controls is stressed since both BAP1 and MTAP testing depend on the loss of staining in neoplastic cells. In conclusion, this paper also recommends a combined approach using multiple markers and careful validation of methods.

1. Monaco SE, Brcic L, Dacic S. State-of-the-art cytology of pleural fluid, focusing on the diagnosis of mesothelioma. Cytopathology. 2022;33(1):57–64.
2. Louw A, van Vliet C, Peverall J, et al. Analysis of early pleural fluid samples in patients with mesothelioma: a case series exploration of morphology, BAP1, and CDKN2A status with implications for the concept of mesothelioma in situ in cytology. Cancer Cytopathol. 2022;130(5):352–362.
3. Girolami I, Lucenteforte E, Eccher A, et al. Evidence-based diagnostic performance of novel biomarkers for the diagnosis of malignant mesothelioma in effusion cytology. Cancer Cytopathol. 2022;130(2):96–109.

Dr. Manucha is a professor at the University of Mississippi Medical Center, Jackson, and Dr. Davey is a professor of pathology and associate dean for graduate medical education at the University of Central Florida, Orlando. Both are members of the CAP Cytopathology Committee.