SURVEILLANCE OF SUB-CENTIMETER SIDE-BRANCH IPMNS: RISK OF INVASIVE DISEASE AND FOLLOW-UP RECOMMENDATIONS.

Objective: Define the risk associated with sub-centimeter Side-Branch Intraductal Papillary Mucinous Neoplasms (SB-IPMN) and propose a surveillance strategy based on this cohort.

Background: SB-IPMNs are increasingly discovered with the growing use of high-fidelity cross-sectional imaging, particularly sub-centimeter (<1cm) lesions. Data are absent regarding the risk of progression in sub-centimeter cysts.

Methods: A prospectively maintained database was queried for SB-IPMNs undergoing non-operative surveillance with >2 cross-sectional imaging studies >6 months apart. Clinically-relevant progression (CR-Progression) has been previously defined by development of symptoms, worrisome/high-risk stigmata, or invasive cancer (IC). Growth >5mm in 2years is considered CR-Progression; size>3cm alone is not.

Results: One-thousand patients were included, 291 (29.1%) with SB-IPMN<1cm. Median follow-up from diagnosis was 7.1 years (IQR 3.2-10.4 years) in sub-centimeter cysts vs. 6.4 years (IQR 2.8-10.0 years) in those >1cm (p=0.090). CR-progression was less common in the sub-centimeter group (7.2% vs. 19%, log-rank p<0.001). Cysts that progressed did so at similar time intervals (Median=3.7 vs. 3.3 years, p=0.707). Sub-centimeter cysts developed both IC (1.4% vs 1.8%, log-rank p=0.608), and high-risk pathology (HGD/IC) at a similar rate ( p=0.198) to larger cysts. Cysts that were initially stable for 5 years of surveillance (n=547) developed high-risk pathology in 4.7% (n=25). This was not different by initial cyst size (log-rank p=0.116). Spline curves demonstrate consistently low risk of HGD/IC across increasing cyst size despite a higher rate of CR-progression. CR-progression criteria best discriminated high-risk patholgogy in sub-centimeter cysts. Rate of size growth did not correlate with high-risk pathology (HR=1.14, 95%CI 0.88-1.50).

Conclusion: Sub-centimeter SB-IPMNs develop malignant potential as frequently as their larger counterparts and do so at similar time courses. Often incidental, sub-centimeter presumed SB-IPMNs are diagnosed at arbitrary points in their disease course, and require similar surveillance duration to their larger counterparts., Rate of growth is not predictive of high-risk pathology. t These cysts do not develop CR-progression as frequently, but such features better discriminate high risk pathology in sub centimeter cysts, making development of such features more concerning when they occur.