Cytologic Characteristics of Circulating Epithelioid Cells in Pancreatic Disease

Background—Circulating epithelioid cells (CECs), also known as circulating tumor/cancer/ epithelial/non-hematologic cells, are a prognostic factor in various malignancies that can be isolated via various protocols. We analyzed the cytomorphologic characteristics of CECs isolated by size in a cohort of patients with benign and malignant pancreatic diseases to determine if cytomorphological features could predict CEC origin. Methods—Blood samples were collected from 9 healthy controls and 171 patients with pancreatic disease presenting for surgical evaluation prior to treatment. Blood was processed with the ScreenCell size-based filtration device. Evaluable CECs were analyzed in a blinded fashion for cytomorphologic characteristics including cellularity, nucleoli, nuclear size/irregularity/variability/ hyperchromasia, and nuclear-cytoplasmic ratio. Statistical differences between variables were analyzed via Fisher's exact test. Results—No CECs were identified in normal healthy controls (n=9). Of the 115 patients with CECs (positive or suspicious), 25 had non-malignant disease and 90 had malignancy. There were no significant differences in any of the cytologic criteria between groups divided by benign versus malignant, neoplastic versus non-neoplastic, or pancreatic ductal adenocarcinoma versus neuroendocrine tumor. Conclusions—CECs were seen in patients with malignant and non-malignant pancreatic disease, but not in healthy controls. There were no morphologic differences between cells from different pancreatic diseases. This suggests that numerous conditions may be associated with CECs in the circulation and that care must be taken not to over-interpret cells identified by cytomorphology as indicative of circulating tumor cells of pancreatic cancer. Additional studies are required to determine the origin and clinical significance of these cells.