{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:54:41Z","timestamp":1790999681322,"version":"4.1.0"},"reference-count":12,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"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":["Diagnostic Cytopathology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Serial pancreatic juice aspiration cytological examination (SPACE) has recently been recognized as a useful method for detecting high\u2010grade pancreatic intraepithelial neoplasia (high\u2010grade PanIN). However, the cytological features of high\u2010grade PanIN are heterogeneous, and some cases remain difficult to diagnose. We examined the cytological findings of two surgically resected cases of high\u2010grade PanIN detected by SPACE. Quantitative image analysis was performed to evaluate nuclear atypia and chromatin heterogeneity. In addition, hyperspectral imaging analysis was conducted in one case to assess intranuclear spectral heterogeneity. Case 1 demonstrated focal high\u2010grade PanIN with relatively mild cytological atypia, whereas Case 2 showed multifocal high\u2010grade PanIN with numerous markedly atypical cells. Despite these differences, both cases shared heterogeneous nuclear chromatin staining within the same epithelial clusters. Image analysis demonstrated significantly increased nuclear area, decreased circularity, decreased mean nuclear brightness, and increased intranuclear brightness standard deviation in Case 2 compared with Case 1, indicating differences in the severity of nuclear atypia. In contrast, overlapping distributions of intranuclear brightness standard deviation were observed in both cases, suggesting shared intranuclear chromatin heterogeneity. Furthermore, hyperspectral imaging analysis demonstrated increased intercellular spectral heterogeneity in high\u2010grade PanIN compared with normal pancreatic ductal epithelium, supporting the presence of chromatin heterogeneity from an optical perspective. Although the cytological appearance of high\u2010grade PanIN varies among cases, nuclear chromatin heterogeneity may represent a common and diagnostically important feature. Image analysis and hyperspectral imaging may provide useful objective approaches for evaluating such heterogeneity.<\/jats:p>","DOI":"10.1002\/dc.70187","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:50:32Z","timestamp":1784616632000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nuclear Chromatin Heterogeneity in High\u2010Grade\n                    <scp>PanIN<\/scp>\n                    Detected by Serial Pancreatic Juice Aspiration Cytological Examination (\n                    <scp>SPACE<\/scp>\n                    ): A Report of Two Cases"],"prefix":"10.1002","volume":"54","author":[{"given":"Miyu","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Diagnostic Pathology St. Marianna University School of Medicine Hospital  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruka","family":"Aoki","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology St. Marianna University School of Medicine Hospital  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Ohya","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology St. Marianna University School of Medicine Hospital  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chie","family":"Okawa","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology St. Marianna University School of Medicine Hospital  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1846-1838","authenticated-orcid":false,"given":"Tomoko","family":"Norose","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology St. Marianna University School of Medicine Hospital  Kawasaki Japan"},{"name":"Department of Pathology, Division of Molecular Pathology St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiya","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology St. Marianna University School of Medicine Hospital  Kawasaki Japan"},{"name":"Department of Pathology, Division of Molecular Pathology St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0915-030X","authenticated-orcid":false,"given":"Kazunari","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3644-3896","authenticated-orcid":false,"given":"Saori","family":"Umezawa","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and General Surgery St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Ida","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and General Surgery St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2116-4958","authenticated-orcid":false,"given":"Shinjiro","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal and General Surgery St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9482-1616","authenticated-orcid":false,"given":"Daiki","family":"Nakaya","sequence":"additional","affiliation":[{"name":"Milk Inc.  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8631-821X","authenticated-orcid":false,"given":"Nobuyuki","family":"Ohike","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology St. Marianna University School of Medicine Hospital  Kawasaki Japan"},{"name":"Department of Pathology, Division of Molecular Pathology St. Marianna University School of Medicine  Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e31823c0b05"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2017.11.007"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-16589-9"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13050945"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.23093"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0000000000002135"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/deo2.177"},{"key":"e_1_2_14_9_1","volume-title":"Guidelines for Cytological Diagnosis","author":"Japanese Society of Clinical Cytology","year":"2015"},{"key":"e_1_2_14_10_1","volume-title":"WHO Reporting System for Pancreaticobiliary Cytopathology","author":"International Agency for Research on Cancer","year":"2022"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_14_12_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2019"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/pin.13438"}],"container-title":["Diagnostic Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dc.70187","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/dc.70187","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dc.70187","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:26:11Z","timestamp":1790997971000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/dc.70187"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":12,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["10.1002\/dc.70187"],"URL":"https:\/\/doi.org\/10.1002\/dc.70187","archive":["Portico"],"relation":{},"ISSN":["8755-1039","1097-0339"],"issn-type":[{"value":"8755-1039","type":"print"},{"value":"1097-0339","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"assertion":[{"value":"2026-05-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}