{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:15:59Z","timestamp":1788221759610,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Noninvasive papillary urothelial carcinoma (NIPUC), currently classified in a two\u2010tier system, frequently exhibits mixed low\u2010 and high\u2010grade morphology. We aimed to determine the impact of histopathologic features on grade and stage progression in mixed NIPUCs. Primary and follow\u2010up bladder specimens (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009106) of 28 patients diagnosed with mixed NIPUC were retrieved. Pathological parameters included biopsy volume, percentages of 2\u2010tier (low\u2010high) and 4\u2010tier (Grade 1\u20134) grades, discohesion, and whirling. Outcome measures were grade trend (decline or incline) and stage progression. The mean age was 65 (range, 35\u201381); all but two were male. Ten patients had a previous biopsy showing pure low\u2010grade NIPUC. Patients with &gt;\u20095% high\u2010grade areas (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200914) were classified as high\u2010grade. The mean distributions of G1\u2010G4 in mixed NIPUCs at zero\u2010point were 42%, 42%, 15%, and 1%, respectively. Tumors with &gt;\u200985% Grade 1 histology didn't exhibit an upward grade trend. Stage progression was significantly associated with tumors containing \u2265\u20095% Grades 3\u20134 (high\u2010grade) areas (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.031). Grade trend was directly correlated with stage progression (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.012). Mixed NIPUC has heterogeneous clinical outcomes: a high proportion of Grade 1 areas (&gt;\u200985%) predicts a non\u2010inclining grade trend, whereas the presence of \u2265\u20095% high\u2010grade (Grades 3 and 4) morphology suggests future stage progression.\n                  <\/jats:p>","DOI":"10.1111\/apm.70238","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:41:00Z","timestamp":1784054460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Can We Foresee Grade and Stage Progression in Mixed Low\u2010 and High\u2010Grade Noninvasive Papillary Urothelial Carcinomas?"],"prefix":"10.1111","volume":"134","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9936-3885","authenticated-orcid":false,"given":"Berna","family":"Karabulut","sequence":"first","affiliation":[{"name":"Department of Pathology Health Sciences University, Gulhane Training and Research Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1750-8789","authenticated-orcid":false,"given":"Osman","family":"Dag","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7747-0460","authenticated-orcid":false,"given":"Kemal","family":"Kosemehmetoglu","sequence":"additional","affiliation":[{"name":"Department of Pathology Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7338-1524","authenticated-orcid":false,"given":"Gunes","family":"Guner","sequence":"additional","affiliation":[{"name":"Department of Pathology Hacettepe University  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Urinary and Male Genital Tumours","author":"WHO Classification of Tumours Editorial Board","year":"2022"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2015.06.045"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000000593"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002077"},{"issue":"1","key":"e_1_2_10_6_1","first-page":"23","article-title":"Prognostic Significance of Mitotic Activity in Noninvasive, Low\u2010Grade, Papillary Urothelial Carcinoma","volume":"38","author":"Akkalp A. K.","year":"2016","journal-title":"Analytical and Quantitative Cytopathology and Histopathology"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.10.008"},{"issue":"7","key":"e_1_2_10_8_1","first-page":"1663","article-title":"Cancer Heterogeneity and Its Biologic Implications in the Grading of Urothelial Carcinoma","volume":"88","author":"Cheng L.","year":"2000","journal-title":"Cancer\u2010 The Journal of American Cancer Society"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-014-1383-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2021.07.003"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2013.11.056"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2022.152079"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.5858\/arpa.2023-0367-OA"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2015.09.007"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000002059"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.15438"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2024.08.013"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2014.154"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2021.10.005"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-023-03625-3"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2025.105904"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13000-017-0639-y"}],"updated-by":[{"DOI":"10.1111\/apm.70251","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000}}],"container-title":["APMIS"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apm.70238","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/apm.70238","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apm.70238","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:55:20Z","timestamp":1785218120000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apm.70238"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/apm.70238"],"URL":"https:\/\/doi.org\/10.1111\/apm.70238","archive":["Portico"],"relation":{},"ISSN":["0903-4641","1600-0463"],"issn-type":[{"value":"0903-4641","type":"print"},{"value":"1600-0463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-03-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70238"}}