The Role of Markedly Elevated Cyst Carcinoembryonic Antigen in Risk-Stratifying Pancreatic Cysts

Carcinoembryonic antigen (CEA) level is currently being used in algorithms of commercially available pancreatic cyst fluid analysis platforms. However, the evidence to date on its role in risk stratification for mucinous lesions is heterogenous. We therefore sought to examine the relationship between the magnitude of CEA elevation and the structural and molecular properties of pancreatic cysts.

All patients who underwent pancreatic cyst fluid analysis at a single institution from 2012 to 2019 were retrospectively examined. Structural features on endoscopic ultrasound were analyzed as a function of cyst fluid CEA. A subset of patients who underwent surgical resection was separately analyzed.

A total of 634 pancreatic cyst fluid samples were obtained from 566 patients. Among all samples, 57% had normal cyst fluid CEA. Of those with elevated CEA, 22% had elevations <1000, 13% between 1000 and 10,000, and 8% > 10,000 ng/mL. The CEA >10,000 group had the highest rates of solid components (P = 0.039), mural nodules (P = 0.044), and mean number of DNA abnormalities (P < 0.001). The overall malignancy rate among all patients with cyst CEA >10,000 ng/mL was 14% (n = 7). Importantly, there was a strong association between the magnitude of the CEA elevation and the number of DNA abnormalities (P < 0.001) and the presence of oncogene mutations (P < 0.001).

In this large dataset of pancreatic cyst fluid aspirates, the magnitude of the CEA elevation was associated with worrisome features. Especially at its most extreme, elevated CEA should be further examined in the assessment of neoplastic risk for patients with an established diagnosis of a mucinous pancreatic cyst.