{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:01:33Z","timestamp":1784952093573,"version":"3.55.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T00:00:00Z","timestamp":1737763200000},"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":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Major mutations (e.g., <jats:italic>KRAS<\/jats:italic>, <jats:italic>GNAS<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, <jats:italic>SMAD4<\/jats:italic>) in pancreatic cyst fluid (PCF) are useful for classifying and risk stratifying certain cyst types, particularly in cases with nondiagnostic cytology. However, the significance of uncommon minor mutations in PCF has yet to be reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In total, 127 PCF specimens (2014\u20132021) from 121 patients that underwent molecular analysis were identified, and detailed clinicopathologic data were recorded. Molecular testing was performed using a laboratory\u2010developed next\u2010generation sequencing panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty\u2010five variants other than <jats:italic>KRAS<\/jats:italic>, <jats:italic>GNAS<\/jats:italic>, <jats:italic>RNF43<\/jats:italic>, <jats:italic>TP53<\/jats:italic>, <jats:italic>CDKN2A<\/jats:italic>, and <jats:italic>SMAD4<\/jats:italic> were detected. Variants that were detected in five or more cases included <jats:italic>ARID1A<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a028), <jats:italic>VHL<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a017), <jats:italic>BRAF<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a012), <jats:italic>ATM<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a08), <jats:italic>APC<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a08), <jats:italic>MEN1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a05), serine threonine kinase 11 <jats:italic>(STK11<\/jats:italic>; <jats:italic>n<\/jats:italic>\u00a0=\u00a05), <jats:italic>PIK3CA<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a05), and <jats:italic>CDH1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a05). Thirty\u2010eight of 121 patients (31%) had histologic confirmation on follow\u2010up resection. Twenty\u2010seven of 28 cysts (96%) with <jats:italic>ARID1A<\/jats:italic> mutations had concurrent <jats:italic>KRAS<\/jats:italic>\/<jats:italic>GNAS<\/jats:italic> mutations; 17 (61%) were diagnosed as neoplastic mucinous cysts on cytology, and 10 (36%) were diagnosed as intraductal papillary mucinous neoplasm (IPMN) on histology (80% low grade). No patients developed disease recurrence or died of disease. Cysts with <jats:italic>STK11<\/jats:italic> mutations had <jats:italic>RAS<\/jats:italic> co\u2010mutations (<jats:italic>KRAS<\/jats:italic>, <jats:italic>n<\/jats:italic>\u00a0=\u00a05; <jats:italic>NRAS<\/jats:italic>, <jats:italic>n<\/jats:italic>\u00a0=\u00a01), and four of those five cysts (80%) were mucinous neoplasms with high\u2010grade atypia on cytology. All three resection specimens were IPMNs with high\u2010grade dysplasia or invasive carcinoma, and two of those patients died of disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In PCFs, <jats:italic>ARID1A<\/jats:italic> mutations were consistently associated with IPMNs (predominantly low grade) with no recurrences or deaths from disease. <jats:italic>STK11<\/jats:italic> mutations appeared to be associated with high\u2010risk mucinous cysts. The detection of minor variants may provide useful preoperative information and add value beyond single\u2010gene genotyping of major mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22935","type":"journal-article","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T11:24:13Z","timestamp":1737804253000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Cytologic, histologic, and clinical correlation of minor mutations in pancreatic cysts"],"prefix":"10.1002","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8598-4485","authenticated-orcid":false,"given":"Melanie C.","family":"Kwan","sequence":"first","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha B.","family":"Pitman","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102016\u2010313586"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.path.2016.04.008"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2015.06.047"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21775"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.09.028"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2013.91"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201014\u20100513"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00161"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2024.100510"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102023\u2010331138"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2023.05.005"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201013\u20100624"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118046108"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1200609"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2514"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3729"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3068"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2628"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21633"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102017\u2010315490"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201017\u20102463"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201006\u20100292"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000005904"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2015.07.041"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2009.725"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)65440\u20105"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.20228"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002\u20109440(10)63053\u20102"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102018\u2010318059"}],"container-title":["Cancer Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.22935","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:57:04Z","timestamp":1760299024000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncy.22935"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,25]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/cncy.22935"],"URL":"https:\/\/doi.org\/10.1002\/cncy.22935","archive":["Portico"],"relation":{},"ISSN":["1934-662X","1934-6638"],"issn-type":[{"value":"1934-662X","type":"print"},{"value":"1934-6638","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,25]]},"assertion":[{"value":"2024-09-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22935"}}