Open journal

ISSN 2471-142X

Worrisome Features for Intraductal Papillary Mucinous Neoplasm: Should We be Worried?

Lorenzo Dioscoridi*

Lorenzo Dioscoridi, MD, PhD

Digestive and Interventional Endoscopy Unit, ASST GOM Niguarda, Milan, Italy; E-mail:

Pancreatic cystic neoplasms include different types of cysts with various biological behavior. The most prevalent are intraductal papillary mucinous neoplasm (IPMN). The majority of IPMN is located in the head of the pancreas. A single cystic mass as well as segmental involvement or involvement of the entire pancreatic duct can be present. 

Management of IPMN should focus on the prevention of malignant progression, while avoiding unnecessary morbidity of surgery. This requires specialized centers with dedicated multidisciplinary teams.

Worrisome features are indicated and described during imaging study of IPMN.

These features, according to 2017 Fukuoka Consensus Guidelines are cyst size ≥3 cm, thickened or enhancing cyst walls, main duct size 5-9 mm, non-enhancing mural nodules, an abrupt change in pancreatic duct caliber with distal pancreatic atrophy, pancreatitis, and lymphadenopathy.1

Although these data represent an indication to perform endoscopic ultrasound study, recent studies have showed that these conditions are not strictly related to high-risk of malignancy.

Izumo et al2 showed that an enhancing mural nodule ≥5 mm, pancreatitis, and thickened/enhancing cyst walls were independent predictive factors for high-grade dysplasia. However, none of worrisome features were pointed out.

Li et al3 described a good correlation for prediction of high-grade dysplasia in presence of high-risk stigmata.

Furthermore, pancreatic resection for worrisome imaging features often demonstrates pathology consistent with low-grade dysplasia.

A recently published multi-institutional study on 324 patients by Wilson et al4 found that 44% of specimens resected according to current guidelines had only low-grade dysplasia.

Sugimoto et al5 confirmed in a single-center, retrospective analysis, that main pancreatic duct diameter of 7.2 mm (one of the high-risk stigmata) was identified as an optimal cutoff for a prognostic factor for malignant disease in IPMN (Table 1).


Table 1. Results of International Studies on Malignant Predictors for IPMN


Number of patients


Izumo et al2


Enhancing mural nodule ≥5 mm, pancreatitis and enhancing cyst walls were independent predictive factors for high-grade dysplasia.
Li et al3


48.3% of patients who met high-risk stigmata were respectively confirmed as high-grade dysplasia.
Wilson et al4


In the absence of high-risk features, high-grade dysplasia was present in 57.4% of patients with 2 or more worrisome features.
Sugimoto et al5


A main pancreatic duct diameter of 7.2 mm or greater was an independent prognostic factor for malignant neoplasms.
Shimizu et al6


On multivariate analysis, existing carcinoma was associated with female gender, main pancreatic duct IPMN, nodule size, and pancreatic juice cytology grade.


Shimizu et al6 developed a nomogram to attempt to predict the probability of the presence of carcinoma in patients with IPMNs. Gender, type of lesion (MD-IPMN vs. BD-IPMN), size of mural nodules and pancreatic fluid cytology were all assigned points: none of them is classified as worrisome feature.

On the base of the recent literature, we can start to consider “worrisome features” as indicators of mostly low-grade dysplasia and we should not based strict follow-up and/or indications to surgery on them.

1. Dbouk M, Brewer Gutierrez OI, Lennon AM, et al. Guidelines on management of pancreatic cysts detected in high-risk individuals: An evaluation of the 2017 Fukuoka guidelines and the 2020 International Cancer of the Pancreas Screening (CAPS) consortium statements. Pancreatology. 2021; 21(3): 613-621. doi: 10.1016/j.pan.2021.01.017

2. Izumo W, Higuchi R, Furukawa T, et al. Importance of each high-risk stigmata and worrisome features as a predictor of high-grade dysplasia in intraductal papillary mucinous neoplasms of the pancreas. Pancreatology. 2020; 20(5): 895-901. doi: 10.1016/j.pan.2020.06.011

3. Li B, Guo SW, Shi XH, et al. Diagnostic efficacy for predicting intraductal papillary mucinous neoplasms of the pancreas with high grade dysplasia or invasive carcinoma based on the surgery indications in different guidelines. Zhonghua Wai Ke Za Zhi. 2021; 59(5): 359-365. doi: 10.3760/cma.j.cn112139-20200507-00365

4. Wilson GC, Maithel SK, Bentrem D, et al. Are the current guidelines for the surgical management of intraductal papillary mucinous neoplasms of the pancreas adequate? A multi-institutional study. J Am Coll Surg. 2017; 224(4): 461-469. doi: 10.1016/j.jamcollsurg.2016.12.031

5. Sugimoto M, Elliott IA, Nguyen AH, et al. Assessment of a revised management strategy for patients with intraductal papillary mucinous neoplasms involving the main pancreatic duct. JAMA Surg. 2017; 152: e163349. doi: 10.1001/jamasurg.2016.3349

6. Shimizu Y, Kanemitsu Y, Sano T, et al. A nomogram for predicting the probability of carcinoma in patients with intraductal papillary-mucinous neoplasm. World J Surg. 2010; 34: 2932-2938. doi: 10.1007/s00268-010-0785-9