{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:53:36Z","timestamp":1760316816843,"version":"build-2065373602"},"reference-count":13,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Neoplastic mucinous cysts (NMC) are premalignant lesions that can be diagnosed on pancreatic cyst fluid (PCF) based on elevated carcinoembryonic antigen or thick extracellular mucin (ECM) without mucinous epithelium. Under the World Health Organization classification, such cases are considered \u201cpancreaticobiliary neoplasm, low\u2010risk\/grade.\u201d This study evaluates the diagnostic accuracy and risk of cysts diagnosed as NMC without mucinous epithelium.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A total of 609 PCF specimens (493 patients) diagnosed as NMC were identified; 279\/609 (45.8%) had no mucinous epithelium: 182 and 61 were diagnosed based only on elevated carcinoembryonic antigen \u2265192 ng\/mL or ECM, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among PCF without mucinous epithelium and with molecular correlation, 110\/165 (66.7%) harbored <jats:italic>KRAS\/GNAS\/RNF43<\/jats:italic> mutations. High\u2010risk mutations (<jats:italic>TP53<\/jats:italic>\/<jats:italic>CDKN2A<\/jats:italic>\/<jats:italic>SMAD4<\/jats:italic>) occurred at similar rates in cysts with low\u2010grade mucinous epithelium as in those without mucinous epithelium (6.5% vs. 3.6%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.224). A total of 63\/71 (88.7%) resections from cysts without mucinous epithelium were confirmed as NMC: 40 (56.3%) had low\u2010grade dysplasia and 23 (32.4%) had at least high\u2010grade dysplasia. A total of 142\/279 (50.9%) PCF without mucinous epithelium were molecularly or histologically confirmed as NMC. No significant differences were found in the rates of new worrisome radiologic features, invasive carcinoma, or disease\u2010related mortality between the groups. Patient survival trended lower in the cohort with mucinous epithelium, though rates were comparable upon subanalysis of only \u201cpancreaticobiliary neoplasm, low\u2010risk\/grade\u201d\u00a0cysts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Even though PCF diagnosed as NMC without mucinous epithelium defaults to a low\u2010risk category, the rates of high\u2010grade neoplasia\/high\u2010risk outcomes are comparable to those with low\u2010grade mucinous epithelium, supporting continued utility of carcinoembryonic antigen and ECM as diagnostic criteria for NMC in the absence of mucinous epithelium.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.70030","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T12:41:08Z","timestamp":1752151268000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic accuracy and risk stratification of pancreatic cyst fluids diagnosed as mucinous neoplasms without mucinous epithelium"],"prefix":"10.1002","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-3096","authenticated-orcid":false,"given":"Priscila","family":"Dias Goncalves","sequence":"first","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8029-4787","authenticated-orcid":false,"given":"M. Lisa","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000005535"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102016\u2010313127"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.02.013"},{"key":"e_1_2_8_5_1","first-page":"629","article-title":"Revisiting the performance of cyst fluid carcinoembryonic antigen as a diagnostic marker for pancreatic mucinous cysts: a comprehensive 20\u2010year institutional review","volume":"73","author":"Kwan MC","year":"2024","journal-title":"Gut"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22681"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-16589-9"},{"key":"e_1_2_8_8_1","article-title":"World Health Organization Joint Editorial Board. WHO Reporting System for Pancreaticobiliary Cytopathology","volume":"2","author":"International Academy of Cytology, International Agency for Research on Cancer","year":"2022","journal-title":"International Agency for Research on Cancer (IAC\u2010IARC\u2010WHO cytopathology reporting systems series"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.22935"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3729"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620\u2010014\u20103254\u20108"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100042\u2010101755"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/mpa.0b013e318033fa12"},{"key":"e_1_2_8_14_1","first-page":"101","article-title":"Pseudocyst of the pancreas: the role of cytology and special stains for mucin","volume":"117","author":"Gonzalez Obeso E","year":"2009","journal-title":"Cancer"}],"container-title":["Cancer Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.70030","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T18:52:30Z","timestamp":1760295150000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncy.70030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":13,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/cncy.70030"],"URL":"https:\/\/doi.org\/10.1002\/cncy.70030","archive":["Portico"],"relation":{},"ISSN":["1934-662X","1934-6638"],"issn-type":[{"type":"print","value":"1934-662X"},{"type":"electronic","value":"1934-6638"}],"subject":[],"published":{"date-parts":[[2025,7,10]]},"assertion":[{"value":"2025-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70030"}}