• Piotr Zelga, Yasmin G Hernandez-Barco, Motaz Qadan, Cristina R Ferrone, Avinash Kambadakone, Nora Horick, Asif Jah, Andrew L Warshaw, Keith D Lillemoe, Anita Balakrishnan, and Carlos Fernández-Del Castillo.
• From the Department of Surgery (Zelga, Qadan, Ferrone, Warshaw, Lillemoe, Fernández-del Castillo), Massachusetts General Hospital and Harvard Medical School, Boston, MA.
• J. Am. Coll. Surg. 2022 Jun 1; 234 (6): 1021-1030.

BackgroundThe 2017 revised International Association of Pancreatology guidelines for management of intraductal papillary mucinous neoplasm (IPMN) describe worrisome features (WF) and high-risk stigmata (HRS), recommending resection in the latter and further work-up and close surveillance for patients with WF. The effect of multiple WF on the likelihood of malignancy has not been evaluated.Study DesignEight hundred ten patients who underwent pancreatic resection for IPMN in 2 tertiary referral centers were identified from prospective institutional databases. Patients were retrospectively categorized into subgroups according to the number of WF or HRS and presence of malignancy, defined as high-grade dysplasia (HGD) or invasive cancer on final pathology.ResultsThree hundred seventy-nine (47%) patients had HRS, 370 (46%) had 1 or more WF, and 61 patients (7%) had neither. Malignancy was present in 70% (n = 267) of patients with HRS and in 30% (n = 127) of those with WF. Only 3 of 61 patients without WF/HRS had malignancy, and all only in the form of HGD. The risk of malignancy increased in a stepwise fashion with the number of WF, to 22%, 34%, and 59% with 1, 2, and 3 WF, respectively (p = 0.001), and reached 100% in patients with 4 or more WF. Although the relative risks differed for particular WF, the areas under the curve were not statistically different.ConclusionWe confirm that presence of HRS in IPMN is associated with a very high likelihood of malignancy. The presence of a single WF has a malignancy risk of 22%, and additional WF increase this risk significantly. When 3 or more WF are present, the risk is similar to that of HRS.Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.

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