Clinicopathological Characteristics and Long-Term Outcomes of Cystic vs. Solid Pancreatic Neuroendocrine Tumors: A Multi-Institutional Experience with 1727 Patients

Objective: To investigate the clinicopathological features and long-term outcomes of cystic and solid pancreatic neuroendocrine tumors (PanNETs).

Summary background data: PanNETs uncommonly present as cystic lesions. Whether cystic PanNETs represent a distinct clinical entity compared to solid PanNETs is controversial.

Methods: Clinicopathologic data of patients with resected PanNETs were collected from 4 high-volume centers between 2000-2019. Clinicopathological characteristics and outcomes of patients with cystic and solid PanNETs were compared based on a 3 cm tumor size cut-off using the Chi-squared test and Mann-Whitney U test. Survival estimates were calculated with the Kaplan-Meier method and log-rank test and multivariable analysis using a Cox proportional hazard model.

Results: Of the 1727 patients undergoing pancreatectomy for PanNET, the median age was 58.1 years (IQR, 18.4), and 53.3% were male. Of these, 177 (10.3%) were cystic and 1550 (89.7%) solid. Cystic PanNETs were more prevalent in patients with hereditary syndromes, less frequently functional, and more often located in the body/tail of the pancreas. After the exclusion of patients with functional tumors, WHO G3 tumors, hereditary syndromes, neoadjuvant treatment, and metastatic stage, 145 cystic PanNETs were compared to 1059 solid PanNETs, and the median follow-up period of the cohort was 64 months. Cystic PanNETs demonstrated significantly fewer high-risk histopathological features, lymph node metastases (5.5% vs. 24.0%, P<0.001), and distant recurrence (4.1% vs. 14.4%; P<0.001). Among tumors ≤3 cm, cystic PanNETs had a low rate of lymph node metastases (3.9% vs. 17.8%; P<0.001), recurrence (3.1% vs. 8.4%; P=0.041), and low propensity to recur distantly. Cystic PanNETs had favorable long-term survival regardless of tumor size.

Conclusion: Cystic PanNETs have a more benign course than their solid counterparts and conservative management can be considered for EUS-FNA-proven cystic PanNETs ≤3 cm. Parenchyma and lymph-node sparing resections are warranted in patients with cystic PanNETs>3 cm. Patients with poor baseline performance status may forego cystic PanNET resection and not affect their overall survival.