PMID- 35143119 OWN - NLM STAT- MEDLINE DCOM- 20220509 LR - 20220531 IS - 1934-6638 (Electronic) IS - 1934-662X (Linking) VI - 130 IP - 5 DP - 2022 May TI - 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. PG - 352-362 LID - 10.1002/cncy.22548 [doi] AB - BACKGROUND: The concept of mesothelioma in situ has been revisited and is a new World Health Organization diagnostic entity. The definition centers on ancillary techniques used in pleural mesothelioma (PM) assessment. At the authors' institution, most PM diagnoses are made on cytologic specimens. Effusion samples obtained before definitive PM diagnosis were interrogated using BRCA1-associated protein 1 gene (BAP1), cyclin-dependent kinase inhibitor 2A gene (CDKN2A) and cytologic evaluation to assess whether early or possible in situ disease could be characterized. METHODS: All cases of PM diagnosed between January 2008 and December 2019 were identified at a tertiary referral center. Patients who had a pleural fluid sample collected 24 months before the diagnosis were selected, numbering 8 in total. The cytomorphology of each sample was reviewed; and, retrospectively, BAP1 immunohistochemistry (IHC) and CDKN2A fluorescence in situ hybridization (FISH) were performed on initial and diagnostic samples. RESULTS: The initial samples were deemed benign in 5 cases and atypical mesothelial proliferations in 3 cases. A spectrum of apparently normal to atypical cytomorphologic changes was identified. BAP1 loss was present in 6 of 8 initial cases, whereas CDKN2A homozygous deletion was identified in 1 of 7 initial cases. Either abnormality was identified in 7 of 8 initial samples. CONCLUSIONS: Detectable abnormalities of BAP1 IHC and CDKN2A FISH were present in pleural fluid specimens before the development of cytomorphologic features diagnostic of PM. This is the largest series to date describing cytology samples early in the course of PM development, thereby highlighting a possible cytological equivalent for mesothelioma in situ. CI - (c) 2022 American Cancer Society. FAU - Louw, Amber AU - Louw A AD - Department of Anatomical Pathology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Center, Nedlands, Western Australia, Australia. AD - School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia. AD - Institute for Respiratory Health, Nedlands, Western Australia, Australia. AD - National Center for Asbestos Related Diseases, University of Western Australia, Nedlands, Western Australia, Australia. FAU - van Vliet, Chris AU - van Vliet C AD - Department of Anatomical Pathology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Center, Nedlands, Western Australia, Australia. FAU - Peverall, Joanne AU - Peverall J AD - Department of Diagnostic Genomics, PathWest Laboratory Medicine, Queen Elizabeth II Medical Center, Nedlands, Western Australia, Australia. FAU - Colkers, Shane AU - Colkers S AD - Department of Anatomical Pathology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Center, Nedlands, Western Australia, Australia. FAU - Acott, Nathan AU - Acott N AD - Department of Anatomical Pathology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Center, Nedlands, Western Australia, Australia. FAU - Creaney, Jenette AU - Creaney J AD - Institute for Respiratory Health, Nedlands, Western Australia, Australia. AD - National Center for Asbestos Related Diseases, University of Western Australia, Nedlands, Western Australia, Australia. AD - Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. FAU - Lee, Y C Gary AU - Lee YCG AD - Institute for Respiratory Health, Nedlands, Western Australia, Australia. AD - Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. AD - School of Medicine, University of Western Australia, Nedlands, Western Australia, Australia. FAU - Chai, Siaw Ming AU - Chai SM AUID- ORCID: 0000-0002-7941-5561 AD - Department of Anatomical Pathology, PathWest Laboratory Medicine, Queen Elizabeth II Medical Center, Nedlands, Western Australia, Australia. LA - eng PT - Journal Article DEP - 20220210 PL - United States TA - Cancer Cytopathol JT - Cancer cytopathology JID - 101499453 RN - 0 (BAP1 protein, human) RN - 0 (Biomarkers, Tumor) RN - 0 (CDKN2A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (Tumor Suppressor Proteins) RN - EC 3.4.19.12 (Ubiquitin Thiolesterase) SB - IM MH - Biomarkers, Tumor/metabolism MH - Cyclin-Dependent Kinase Inhibitor p16/genetics MH - Homozygote MH - Humans MH - In Situ Hybridization, Fluorescence MH - *Lung Neoplasms/diagnosis/genetics MH - *Mesothelioma/diagnosis/genetics MH - *Mesothelioma, Malignant MH - *Pleural Neoplasms/diagnosis/genetics MH - Retrospective Studies MH - Sequence Deletion MH - Tumor Suppressor Proteins/genetics MH - Ubiquitin Thiolesterase/genetics OTO - NOTNLM OT - BRCA1-associated protein 1 (BAP1) OT - cyclin-dependent kinase inhibitor 2A gene (CDKN2A) OT - cytology OT - mesothelioma OT - mesothelioma in situ EDAT- 2022/02/11 06:00 MHDA- 2022/05/10 06:00 CRDT- 2022/02/10 12:17 PHST- 2021/11/11 00:00 [revised] PHST- 2021/09/10 00:00 [received] PHST- 2021/11/29 00:00 [accepted] PHST- 2022/02/11 06:00 [pubmed] PHST- 2022/05/10 06:00 [medline] PHST- 2022/02/10 12:17 [entrez] AID - 10.1002/cncy.22548 [doi] PST - ppublish SO - Cancer Cytopathol. 2022 May;130(5):352-362. doi: 10.1002/cncy.22548. Epub 2022 Feb 10.