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For diagnosing PM, a three\u2010step approach is used: (1) detecting atypical cells; (2) verifying their mesothelial origin using immunohistochemistry (IHC); and (3) discriminating PM from benign mesothelial proliferations (BMP). The third step is critical for diagnosing early lesions. In small biopsy or cytologic specimens in which tumor cell fat invasion cannot be assessed, genomic\u2010based assays, including IHC\u2010detected BAP1 loss and fluorescence in situ hybridization (FISH)\u2010detected homozygous deletion (HD) of <jats:italic>CDKN2A\/p16<\/jats:italic>, are effective for differentiation. Both BAP1 IHC and <jats:italic>CDKN2A<\/jats:italic> FISH can equally be applied to histologic and cytologic specimens, with 100% specificity in discriminating PM from BMP. We found that methylthioadenosine phosphorylase (MTAP) loss as detected by IHC could serve as a feasible alternative in tissue and cytologic preparations for <jats:italic>CDKN2A<\/jats:italic> FISH. However, a combination including FISH was still most effective: the addition of <jats:italic>NF2<\/jats:italic> FISH to <jats:italic>CDKN2A<\/jats:italic> FISH and BAP1 IHC yielded a greater sensitivity of close to 100% in diagnosing PM tissues. Although IHC is more feasible than FISH, owing to remaining challenges in data interpretation, caution and familiarity are warranted when diagnosing PM.<\/jats:p>","DOI":"10.1111\/pin.13235","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T12:10:25Z","timestamp":1653135025000},"page":"389-401","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Update of pathological diagnosis of pleural mesothelioma using genomic\u2010based morphological techniques, for both histological and cytological investigations"],"prefix":"10.1111","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0691-1222","authenticated-orcid":false,"given":"Kazuki","family":"Nabeshima","sequence":"first","affiliation":[{"name":"Department of Pathology Fukuoka University School of Medicine and Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-3888","authenticated-orcid":false,"given":"Makoto","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"Department of Pathology Fukuoka University School of Medicine and Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kinoshita","sequence":"additional","affiliation":[{"name":"Department of Pathology Fukuoka University School of Medicine and Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Pathology Fukuoka University School of Medicine and Hospital Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5090-6594","authenticated-orcid":false,"given":"Prakasit","family":"Sa\u2010ngiamwibool","sequence":"additional","affiliation":[{"name":"Department of Pathology Fukuoka University School of Medicine and Hospital Fukuoka Japan"},{"name":"Department of Pathology Faculty of Medicine, Khon Kaen University Khon Kean Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1002845"},{"key":"e_1_2_13_3_1","unstructured":"Environmental Restoration and Conservation Agency [Internet]. 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