{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T07:19:42Z","timestamp":1764832782235,"version":"3.46.0"},"reference-count":13,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"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":["Pathology International"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    We report a case of pancreatic ductal adenocarcinoma (PDAC) in a 51\u2010year\u2010old woman with\n                    <jats:italic>PRSS1<\/jats:italic>\n                    \u2010associated hereditary pancreatitis (HP) and a history of chronic alcohol and tobacco use. Following neoadjuvant chemotherapy, she underwent total pancreatectomy. Histological analysis of the entire pancreas revealed no high\u2010grade PanINs and scattered low\u2010grade PanINs, with and without\n                    <jats:italic>KRAS<\/jats:italic>\n                    mutations, indicating molecular heterogeneity. Genomic profiling identified multiple driver alterations, comprising both clonal and subclonal events, including mutations in\n                    <jats:italic>KRAS, CDKN2A\/B, SMAD4, ATRX, MSH3<\/jats:italic>\n                    , and the\n                    <jats:italic>TERT<\/jats:italic>\n                    promoter. Immunohistochemistry showed strong nuclear p53 overexpression despite the absence of\n                    <jats:italic>TP53<\/jats:italic>\n                    mutation, suggesting a chromosomal instability phenotype. These findings support the hypothesis of a chromothripsis\u2010like catastrophic genomic event contributing to rapid oncogenesis, bypassing the conventional PanIN sequence. The background of chronic inflammation, advanced lipomatous atrophy, and environmental exposures may have facilitated this transformation. This case underscores the need to consider alternative, nonlinear pathways of PDAC development in genetically predisposed individuals and highlights the potential utility of molecular surveillance for early detection and risk stratification.\n                  <\/jats:p>","DOI":"10.1111\/pin.70055","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T12:38:46Z","timestamp":1760445526000},"page":"586-592","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Case of Pancreatic Ductal Adenocarcinoma in\n                    <i>PRSS1<\/i>\n                    \u2010Associated Hereditary Pancreatitis in the Absence of High\u2010Grade PanIN: Suggestive of Chromothripsis\u2010Like Tumor Evolution"],"prefix":"10.1111","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1846-1838","authenticated-orcid":false,"given":"Tomoko","family":"Norose","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology, Department of Pathology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8631-821X","authenticated-orcid":false,"given":"Nobuyuki","family":"Ohike","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Department of Pathology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunari","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Sunakawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiya","family":"Sugiura","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Department of Pathology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirotaka","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology, Department of Pathology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9026-244X","authenticated-orcid":false,"given":"Junki","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Pathology St. Marianna University School of Medicine Kawasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16134-7"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(04)00013-8"},{"key":"e_1_2_12_4_1","article-title":"Pancreatic Cancer Risk in Hereditary Pancreatitis","volume":"5","author":"Kiraly T. W.","year":"2014","journal-title":"Frontiers in Physiology"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2009.09.009"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000164"},{"key":"e_1_2_12_7_1","first-page":"856","article-title":"A Family of the Hereditary Pancreatitis Discovered During Treatment of Diabetes Mellitus","volume":"54","author":"Kato H.","year":"2011","journal-title":"Diabetes"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-86152-y"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0804385"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/1457452"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7744"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41417-024-00768-6"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/2025.04.17.649416"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31723"}],"container-title":["Pathology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pin.70055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T06:29:10Z","timestamp":1764829750000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pin.70055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":13,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/pin.70055"],"URL":"https:\/\/doi.org\/10.1111\/pin.70055","archive":["Portico"],"relation":{},"ISSN":["1320-5463","1440-1827"],"issn-type":[{"type":"print","value":"1320-5463"},{"type":"electronic","value":"1440-1827"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"2025-08-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}