Unraveling the Long-term Natural History of Branch Duct Intraductal Papillary Mucinous Neoplasm: Beyond 10 years

Objective: To describe the long-term natural history of Branch duct intraductal papillary mucinous neoplasm (BD-IPMN). Background: The BD-IPMN is a known precursor of pancreatic cancer, yet its long-term natural history is largely unknown. Methods: We retrospectively reviewed patients with BD-IPMN who were followed at the Massachusetts General Hospital for at least ten years without surgical intervention. Patient and cyst characteristics, development of worrisome features (WF), need for surgery, and malignancy were recorded. The risk of pancreatic cancer in this cohort was compared with the general population by determining the Standardized Incidence Ratio (SIR). Results: 316 patients with BD-IPMN who were followed for at least ten years without intervention were identified. The median age was 63 years, and the median follow-up was 13.5 years (range 10 – 28.8 years). Median cyst size at diagnosis was 1.2 cm (IQR 0.8 – 1.7), was 1.8 cm (IQR 1.2-2.6) at ten years, and increased to 2.0 cm (IQR 1.3 – 3.0) by the end of surveillance. At the 10-year mark, 24% of patients had WF, and by the end of surveillance, an additional 20% had developed WF or high-risk stigmata. 8.2% of patients developed pancreatic malignancy (high-grade dysplasia or invasive cancer). The SIR for pancreatic cancer was 9.28 (95%CI of 5.82 – 14.06), with almost two-thirds of invasive cancers occurring within the pancreatic cyst. Conclusions: After ten years of surveillance for BD-IPMN without intervention, the disease continues to progress and one of every 12 patients will develop malignancy. The risk of pancreatic cancer appears to be nine times higher than in the comparable age-matched population.