{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:12:00Z","timestamp":1791090720037,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,2,28]],"date-time":"2013-02-28T00:00:00Z","timestamp":1362009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>In malignant pleural mesothelioma (MPM), most patients first present with pleural effusion; thus, cytologic analysis is the primary diagnostic approach. However, the cytologic distinction between MPM and reactive mesothelial cells (RMCs) in effusions can be extremely difficult due to the lack of both well\u2010established immunocytochemical markers and definite cytological criteria for MPM. Moreover, the existence of both MPM cells and RMCs in effusions from the same patient makes the differentiation even more challenging. Homozygous deletion of the 9p21 locus, the site of the cyclin\u2010dependent kinase inhibitor 2A\/p16 (<jats:italic>CDKN2A\/p16<\/jats:italic>) gene, frequently occurs in MPM but has never been reported in RMCs. The aim of this study was to define the cytomorphological characteristics of MPM cells, identified by the presence of 9p21 homozygous deletion by fluorescence in situ hybridization (FISH).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>For this purpose, cells on smear preparations were recorded using a virtual microscope system and were subjected to FISH analysis. Thereafter, 9p21 homozygous deletion\u2010positive cells were identified in the recorded virtual slides, followed by analysis of their morphological characteristics.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Mesothelioma cells positive for the 9p21 homozygous deletion exhibited significantly more frequent cell\u2010in\u2010cell engulfment, multinucleation (more than 2 nuclei), and larger multicellular clusters composed of more than 10 cells than did 9p21 deletion\u2010negative RMCs. Possible cutoff values are also proposed for these morphological markers to differentiate MPM cells from RMCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>These morphological differences and cutoff values are useful for cytological differentiation of mesothelioma cells from RMCs. In addition, the novel technique of a combination of virtual microscopy and FISH is introduced for tumor morphological analysis. <jats:bold><jats:italic>Cancer (Cancer Cytopathol)<\/jats:italic> 2013;121:415\u201322.<\/jats:bold> \u00a9 <jats:italic>2013 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21269","type":"journal-article","created":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T05:15:01Z","timestamp":1362114901000},"page":"415-422","source":"Crossref","is-referenced-by-count":53,"title":["Morphology of 9p21 homozygous deletion\u2010positive pleural mesothelioma cells analyzed using fluorescence in situ hybridization and virtual microscope system in effusion cytology"],"prefix":"10.1002","volume":"121","author":[{"given":"Shinji","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Department of Pathology Fukuoka University Hospital and School of Medicine Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Nabeshima","sequence":"additional","affiliation":[{"name":"Department of Pathology Fukuoka University Hospital and School of Medicine Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Kamei","sequence":"additional","affiliation":[{"name":"Division of Pathology Yamaguchi Grand Medical Center Hofu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenzo","family":"Hiroshima","sequence":"additional","affiliation":[{"name":"Department of Pathology Tokyo Women's Medical University Yachiyo Medical Center Yachiyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunimitsu","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Pathology Osaka Prefectural Hospital Organization Osaka Prefectural Medical Center for Respiratory and Allergic Disease Habikino Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakae","family":"Hata","sequence":"additional","affiliation":[{"name":"Department of Pathology Kawasaki Medical School Hospital Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuji","family":"Marukawa","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Hokkaido University Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Matsuno","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology Hokkaido University Hospital Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Laboratory National Kyushu Cancer Center Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Tsujimura","sequence":"additional","affiliation":[{"name":"Department of Pathology Hyogo College of Medicine Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra050152"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.8523"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000056290"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2007.081430"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.09-1951"},{"key":"e_1_2_7_7_1","first-page":"5547","article-title":"p16 alterations and deletion mapping of 9p21\u2010p22 in malignant mesothelioma","volume":"54","author":"Cheng JQ","year":"1994","journal-title":"Cancer Res"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.45"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2010.076794"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/23.7.1127"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10923"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-008-0689-3"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23413"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1827.2010.02534.x"},{"key":"e_1_2_7_15_1","volume-title":"World Health Organization Classification of Tumours. 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