{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T11:01:57Z","timestamp":1771844517105,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,12,10]],"date-time":"2015-12-10T00:00:00Z","timestamp":1449705600000},"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":[[2016,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Differentiated squamous intraepithelial neoplasia (<jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content>) has been described in several sites, including the upper aerodigestive tract and vulva, so this study investigated whether it also occurred in the anal canal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>All cases of squamous cell carcinoma (<jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content>) involving the anal canal diagnosed between 2009 and 2015 at our institution were reviewed. Eighty\u2010six cases were included, and 13 (15%) showed features consistent with <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content>: 10 were \u2018pure\u2019 <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content>, and three were \u2018mixed\u2019 <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content> and squamous intraepithelial lesion. <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content> was characterized by atypical keratinocytes limited to the basal\/parabasal layers, acanthosis, and a \u2018cobblestone\u2019 appearance. Among specimens with pure <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content>, the surface was flat in eight cases. In five cases, the <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content> was extensive, and associated with deeply invasive <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> requiring radical surgical resection. Immunohistochemically, the epithelia showing changes consistent with <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content> were p16\u2010negative, whereas the invasive component was p16\u2010positive in 12 cases. Both Ki67 and p53 showed strong nuclear positivity in the basal\/parabasal layers of <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Invasive <jats:styled-content style=\"fixed-case\">SCC<\/jats:styled-content> associated with <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content> often presents at an advanced stage of disease, requiring radical surgical treatment. The neoplastic changes in <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content> are limited to the basal\/parabasal layers, which may account for the negative diagnoses by anal cytopathology and late clinical diagnosis. The recognition of anal <jats:styled-content style=\"fixed-case\">DSIN<\/jats:styled-content> is important in order to avoid underdiagnosis in superficial biopsies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.12874","type":"journal-article","created":{"date-parts":[[2015,9,24]],"date-time":"2015-09-24T13:32:56Z","timestamp":1443101576000},"page":"834-842","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Differentiated squamous intraepithelial neoplasia associated with squamous cell carcinoma of the anal canal"],"prefix":"10.1111","volume":"68","author":[{"given":"Jason K","family":"Wasserman","sequence":"first","affiliation":[{"name":"Pathology and Laboratory Medicine The Ottawa Hospital and University of Ottawa Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin","family":"Bateman","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine The Ottawa Hospital and University of Ottawa Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kien T","family":"Mai","sequence":"additional","affiliation":[{"name":"Pathology and Laboratory Medicine The Ottawa Hospital and University of Ottawa Ottawa Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,12,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12574"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-7435(03)00013-6"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26115"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.aids.0000181012.62385.4a"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00384-001-0369-0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PGP.0b013e31826916c7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004347-200001000-00004"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200003000-00013"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-013-1412-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1066896913512866"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2005.02036.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/pgp.0b0318134ea34"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200211000-00001"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAI.0000000000000080"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02234299"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-015-1725-8"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2015.20"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28580"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1438.2006.00355.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.91"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2009.179"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.21242"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d6818"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.12874","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.12874","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T15:26:50Z","timestamp":1696346810000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.12874"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,10]]},"references-count":23,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1111\/his.12874"],"URL":"https:\/\/doi.org\/10.1111\/his.12874","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,10]]},"assertion":[{"value":"2015-05-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-09-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-12-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}