Surveillance of subcentimeter side-branch intraductal papillary mucinous neoplasms: risk of invasive disease and follow-up recommendations

Abstract

Background: Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs) are increasingly recognized with the increasing use of high-fidelity cross-sectional imaging, particularly subcentimeter (<1 cm) lesions. Data regarding the risk of progression in subcentimeter cysts are absent. This study aimed to define the risk associated with subcentimeter SB-IPMNs and to propose a surveillance strategy based on this cohort.

Methods: A prospectively maintained database was queried for patients with SB-IPMN who underwent nonoperative surveillance with ≥2 cross-sectional imaging studies performed >6 months apart. Clinically relevant (CR) progression has been previously defined as the development of symptoms, worrisome/high-risk stigmata, or invasive cancer (IC). Growth of ≥5 mm in 2 years is considered CR progression, whereas size of ≥3 cm alone is not.

Results: A total of 1000 patients were included in the study, of whom 291 (29.1%) had SB-IPMN of <1 cm. The median follow-up times from diagnosis were 7.1 years (IQR, 3.2-10.4) in subcentimeter cysts and 6.4 years (IQR, 2.8-10.0) in cysts of ≥1 cm (P =.090). CR progression was less common in the subcentimeter cyst group than in the larger cyst group (7.2% vs 19.0%, respectively; log-rank P <.001). Cysts that progressed did so at similar time intervals (median: 3.7 years in the subcentimeter cyst group vs 3.3 years in the larger cyst group; P =.707). The subcentimeter cyst group developed IC (1.4% in the subcentimeter cyst group vs 1.8% in the larger cyst group; log-rank; P =.608) and high-risk pathology (high-grade dysplasia [HGD]/IC) at a similar rate as the larger cyst group (P =.198). Of 547 patients with cysts that were initially stable for 5 years of surveillance, 25 (4.7%) developed high-risk pathology. This was not different by initial cyst size (log-rank P =.116). Spline curves demonstrated consistently low risk of HGD/IC across increasing cyst size despite a higher rate of CR progression. The CR progression criteria best discriminated high-risk pathology in subcentimeter cysts. The rate of size growth did not correlate with high-risk pathology (hazards ratio, 1.14; 95% CI, 0.88-1.50).

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

Keywords: Cyst surveillance; Intraductal papillary mucinous neoplasm; Pancreatic cancer; Pancreatic cyst.