Increase in Branched Duct IPMN Lesion Size During Surveillance Is Not Associated With Other High-Risk Features: A Multi-Center Study

Abstract

Introduction: Branched duct intraductal papillary mucinous neoplasms (BD-IPMNs) are the most common type of incidental pancreatic cysts. Cyst growth on follow-up imaging remains a concerning sign and usually prompts more rigorous surveillance or surgical resection. The significance of size changes of BD-IPMNs over time remains unclear. The aim of this study is to find predictors of cyst growth and whether rapid cyst growth is associated with increased risk of malignancy. Methods: This is a retrospective study of BD-IPMN patients managed at 2 high-volume referral centers. Patients were included if they were followed for more than 6 months and underwent pancreatic imaging at least twice. Cyst size on imaging studies was calculated by averaging the major and minor axis dimensions. Mean cyst growth rate percentage (MGRP) was calculated as: (final size − initial size)/(initial size)*(100/years) in order to reflect initial cyst size. Rapid cyst growth was defined as a mean cyst growth rate percentage (MGRP) ≥20% per year. Results: Between 1996 and 2013, 326 patients were diagnosed with BD-IPMNs; 168 met inclusion criteria and were followed for a median of 24 months (range: 6.1-114.5 months). Mean age was 64.7±12.1 years; 101 (60.1%) were men. Mean cyst size at baseline (MCSB) was 15.72±9.3 mm. During follow- up, 76 (45.2%) showed an increase in size, of which 27 cysts (35.5%) exhibited rapid growth, with MGRP ≥20% per year occurring in older patients (68.89 years vs. 63.88 years; p=0.04). Rapid cyst growth was not associated with family history of pancreatic disease, smoking, alcohol intake, development of interval symptoms, and cyst characteristics such as baseline size, multiplicity, location, presence of mural nodules or septae, and mean cyst fluid CEA level (4407.6 ng/mL vs. 1863.2 ng/mL; p=0.28). Cyst fluid from 107 cysts was sent for DNA analysis and showed K-ras mutations in 27. Compared to K-ras negative cysts neither MCSB (16.59 mm vs. 17.83 mm) nor MGRP (6.53% per year vs. 3.71% per year) was significantly different. Similar results were observed in cysts with high DNA levels (≥40 ng/uL) or ≥2 allelic imbalance mutations. Eighteen patients underwent surgery during follow-up; 15 (83.3%) patients had low-grade dysplasia (LGD), and 3 had advanced neoplasia (1 high-grade dysplasia and 2 with invasive carcinoma). None of the 3 cysts with advanced neoplasia had MGRP ≥20% per year. Conclusion: BD-IPMNs grow in a significant proportion of patients. However, a significant increase in cyst size was not associated with other high-risk patient or cyst characteristics. Cyst fluid tumor markers do not predict which lesions are likely to grow rapidly. Rapid growth of BD-IPMNs was not associated with advanced neoplasia on surgical pathology.