Related Experiment Video
Updated: Jan 7, 2026
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Molecular Analysis of Mixed-Type and Branch-Duct Intraductal Papillary Mucinous Neoplasms
Amudhan Kannan1, Gilbert Z Murimwa1, John C Mansour1
1Pancreatic Cancer Prevention Program, University of Texas Southwestern Medical Center, Dallas.
Importance:
Studying the molecular profiles of mixed-type and branch-duct (BD) intraductal papillary mucinous neoplasms (IPMNs) is important to understand the underlying biological basis for higher malignant potential of mixed-type IPMNs.
Objective:
To compare mutation patterns in mixed-type vs BD-IPMNs through cyst fluid next-generation sequencing (NGS) analysis using PancreaSeq NGS.
Design, Setting, And Participants:
For this cohort study, pancreatic cyst fluid specimens from 31 medical centers were sent to a centralized NGS lab for analysis between January 2018 and February 2020. Patients with IPMNs (based on KRAS and GNAS mutant status) and with available main pancreatic duct (MPD) size data were included. Patients with main-duct IPMNs and with MPD 10 mm or greater were excluded. Mixed-type IPMNs were defined as IPMNs with an MPD of 5 to 9 mm, and BD-IPMNs were defined as IPMNs with an MPD less than 5 mm. High-risk mutations (HRMs) were categorized as alterations in TP53, SMAD4, CTNNB1, and mTOR genes. Advanced neoplasia was defined as IPMNs with invasive carcinoma or high-grade dysplasia. Data were analyzed from June 1 to 5, 2025.
Main Outcomes And Measures:
Primary outcomes included rates of HRMs and the co-occurrence of 2 or more HRMs in mixed-type IPMNs and BD-IPMNs.
Results:
Among 674 patients with IPMNs, 202 had mixed-type IPMN, and 472 had BD-IPMN. There were 379 female patients (56.2%) and 295 male patients (43.8%); the mean (SD) age was 70.3 (9.6) years. HRMs were observed in 106 patients (16%), with TP53, SMAD4, and MTOR mutations more common in mixed-type IPMNs. Of the 674 patients, 167 patients underwent surgical resection, and these 167 patients had final surgical pathology available. Overall, mixed-type IPMNs had significantly higher rates of HRMs (62 [31%] vs 44 [9.3%]; P < .001) and co-occurrence of 2 or more HRMs (25 [12.4%] vs 14 [3%]; P < .001) compared with BD-IPMNs. On multivariate logistic regression, mixed-type IPMNs were independently associated with HRMs (odds ratio, 3.42; 95% CI, 1.72-6.82). Preoperative NGS detection of HRMs showed 90% sensitivity, 100% specificity, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 86% for predicting advanced neoplasia in mixed-type IPMNs. The presence of any worrisome feature or high-risk stigmata showed a sensitivity of 100%, very low specificity of 13.3%, PPV of 67%, and NPV of 100%.
Conclusions And Relevance:
This study found that mixed-type IPMNs are more likely to harbor HRMs associated with advanced neoplasia. Cyst fluid NGS is highly sensitive and specific for predicting advanced neoplasia in patients with mixed-type IPMNs and should therefore be considered to help upgrade or downgrade risk based on the presence or absence of other worrisome features.
