{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T04:01:55Z","timestamp":1784952115773,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T00:00:00Z","timestamp":1474329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The diagnosis of a pancreatic cyst as mucinous or high\u2010risk dictates the need for follow\u2010up or surgery. Molecular analysis of aspirated pancreatic cyst fluid (PCF) can provide valuable information not obtained by carcinoembryonic antigen (CEA) analysis or cytology.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>All patients who underwent molecular analysis of PCF between March 2013 and June 2015 were reviewed, including pathology, imaging, and follow\u2010up. Molecular testing was performed using a patented, anchored multiplex polymerase chain reaction next\u2010generation sequencing (NGS) platform, which sequenced numerous hotspots in 39 genes linked with malignancy. Performance of NGS and cytology was calculated using final outcome, as determined by clinicopathologic follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The study cohort included 113 PCFs from 105 patients. In total, 119 variants were detected in 67 PCFs (59%). Variants were more common in intraductal papillary mucinous neoplasms (IPMNs)\/cancer than in nonmucinous cysts (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.005). The inclusion of v\u2010Ki\u2010ras2 Kirsten rat sarcoma viral oncogene homolog (<jats:italic>KRAS<\/jats:italic>)\/guanine nucleotide\u2010binding protein (<jats:italic>GNAS<\/jats:italic>) variants improved the classification of IPMNs as mucinous from 50% by microscopy to 100%. Seventy\u2010five percent of cancers had high\u2010grade atypia versus 0% of IPMNs and nonmucinous cysts (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.002). Variants in tumor protein 53 (<jats:italic>TP53<\/jats:italic>), SMAD family member 4 (<jats:italic>SMAD4<\/jats:italic>), cyclin\u2010dependent kinase inhibitor 2A (<jats:italic>CDKN2A<\/jats:italic>), and notch1 (<jats:italic>NOTCH1<\/jats:italic>) were detected only in malignant cysts. Cytology was similarly specific (100%) for detecting malignant cysts but was more sensitive than the identification of late mutations by NGS (75% vs 46%).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The detection of <jats:italic>KRAS<\/jats:italic>\/<jats:italic>GNAS<\/jats:italic> variants improves the identification of mucinous neoplasms. Variants in <jats:italic>TP53, SMAD4, CDKN2A<\/jats:italic>, and <jats:italic>NOTCH1<\/jats:italic> support the diagnosis of a high\u2010risk cyst requiring surgery or additional sampling. Although molecular analysis is not a replacement for cytopathology, it does provide valuable information for accurate preoperative diagnosis, helping to classify mucinous neoplasms and high\u2010risk cysts that require surgical resection. <jats:bold><jats:italic>Cancer Cytopathol<\/jats:italic> 2017;125:41\u201047<\/jats:bold>. \u00a9 <jats:italic>2016 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21775","type":"journal-article","created":{"date-parts":[[2016,9,20]],"date-time":"2016-09-20T09:16:38Z","timestamp":1474362998000},"page":"41-47","source":"Crossref","is-referenced-by-count":106,"title":["Next\u2010generation sequencing adds value to the preoperative diagnosis of pancreatic cysts"],"prefix":"10.1002","volume":"125","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8603-6538","authenticated-orcid":false,"given":"Matthew W.","family":"Rosenbaum","sequence":"first","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology Concord Repatriation General Hospital Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Dudley","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University Stanford California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long P.","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. John","family":"Iafrate","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha B.","family":"Pitman","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.07.3340"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.122"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121317"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gie.2015.06.047"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2007.01516.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2012.04.004"},{"key":"e_1_2_8_8_1","unstructured":"American Gastroenterological Association.Pancreatic cysts. 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