{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:45:35Z","timestamp":1789623935848,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,2,26]],"date-time":"2018-02-26T00:00:00Z","timestamp":1519603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The existence of malignant mesothelioma <jats:italic>in situ<\/jats:italic> (<jats:styled-content style=\"fixed-case\">MIS<\/jats:styled-content>) is often postulated, but there are no accepted morphological criteria for making such a diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Here we report two cases that appear to be true <jats:styled-content style=\"fixed-case\">MIS<\/jats:styled-content> on the basis of <jats:italic>in\u2010situ<\/jats:italic> genomic analysis. In one case the patient had repeated unexplained pleural unilateral effusions. Two thoracoscopies 9 months apart revealed only visually normal pleura. Biopsies from both thoracoscopies showed only a single layer of mildly reactive mesothelial cells. However, these cells had lost <jats:styled-content style=\"fixed-case\">BRCA<\/jats:styled-content>1\u2010associated protein 1 (<jats:styled-content style=\"fixed-case\">BAP<\/jats:styled-content>1) and showed loss of cyclin\u2010dependent kinase inhibitor 2 (<jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>2A) (<jats:italic>p16<\/jats:italic>) by fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridisation (<jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content>). <jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>2<\/jats:italic> was not deleted by <jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content> but 28% of the mesothelial cells showed hyperploidy. Six months after the second biopsy the patient has persisting effusions but no evidence of pleural malignancy on imaging. The second patient presented with ascites and minimal omental thickening on imaging, but no visual evidence of tumour at laparoscopy. Omental biopsy showed a single layer of minimally atypical mesothelial cells with rare tiny foci of superficial invasion of fat. <jats:styled-content style=\"fixed-case\">BAP<\/jats:styled-content>1 immunostain showed loss of nuclear <jats:styled-content style=\"fixed-case\">BAP<\/jats:styled-content>1 in all the surface mesothelial cells and the invasive cells. There was <jats:italic><jats:styled-content style=\"fixed-case\">CDKN<\/jats:styled-content>2A<\/jats:italic> deletion, but no deletion of <jats:italic><jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>2<\/jats:italic> by <jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These cases show that morphologically bland single\u2010layered surface mesothelial proliferations with molecular alterations seen previously only in invasive malignant mesotheliomas exist, and presumably represent malignant <jats:styled-content style=\"fixed-case\">MIS<\/jats:styled-content>. More cases are need to understand the frequency of such changes and the time\u2013course over which invasive tumour develops.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13468","type":"journal-article","created":{"date-parts":[[2018,1,19]],"date-time":"2018-01-19T14:36:39Z","timestamp":1516372599000},"page":"1033-1038","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Malignant mesothelioma <i>in situ<\/i>"],"prefix":"10.1111","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4851-8517","authenticated-orcid":false,"given":"Andrew","family":"Churg","sequence":"first","affiliation":[{"name":"Department of Pathology Vancouver General Hospital and University of British Columbia Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Hwang","sequence":"additional","affiliation":[{"name":"PhenoPath Laboratories Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larry","family":"Tan","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery Faculty of Health Sciences University of Manitoba Winnipeg MB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gefei","family":"Qing","sequence":"additional","affiliation":[{"name":"Department of Pathology Faculty of Health Sciences University of Manitoba Winnipeg MB Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Altaf","family":"Taher","sequence":"additional","affiliation":[{"name":"Department of Pathology Memorial University of Newfoundland St John's NF Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Medicine Memorial University of Newfoundland St John's NF Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana M","family":"Bilawich","sequence":"additional","affiliation":[{"name":"Department of Radiology Vancouver General Hospital and University of British Columbia Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Dacic","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Pittsburgh Medical Center Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,26]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2017.01.009"},{"key":"e_1_2_5_3_1","first-page":"151","article-title":"The concept of mesothelioma in situ: implications for diagnosis and histogenesis","volume":"9","author":"Whitaker D","year":"1992","journal-title":"Semin. Diagn. Pathol."},{"key":"e_1_2_5_4_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1177\/1066896910373927","article-title":"Prominent in situ component in a pleural malignant mesothelioma","volume":"23","author":"Bono F","year":"2015","journal-title":"Int. J. Surg. Pathol."},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/110.3.397"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2012-0112-RA"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2012-201303"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2015-0240-SA"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2015.121"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-005-0005-4"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000176"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.45"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22798"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20317"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208390"},{"key":"e_1_2_5_16_1","first-page":"1","article-title":"Identification of a novel region of homozygous deletion on chromosome 9p in squamous cell carcinoma of the lung: the location of a putative tumor suppressor gene","volume":"57","author":"Wiest JS","year":"1997","journal-title":"Cancer Res."},{"key":"e_1_2_5_17_1","first-page":"225","article-title":"Somatic BRCA1\u2010associated protein 1 (BAP1) loss is an early and rare event in esophageal adenocarcinoma","volume":"7","author":"Loeser H","year":"2017","journal-title":"Mol. Clin. Oncol."},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-15-0330"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.13468","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.13468","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T16:08:56Z","timestamp":1695571736000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.13468"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,26]]},"references-count":17,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1111\/his.13468"],"URL":"https:\/\/doi.org\/10.1111\/his.13468","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,26]]},"assertion":[{"value":"2017-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}