Cytologic characteristics of circulating epithelioid cells in pancreatic disease

Abstract

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.

Cytology and cell‐block immunohistochemistry of circulating tumour cells

“…It is possible that other researchers have found megakaryocytes while looking for CTCs but have not recognised them. Images of megakaryocyte‐like cells have been published in at least one previous paper on CTCs . In the current study, we also found that megakaryocytes were more common in patients with carcinoma than in healthy volunteers.…”

“…one previous paper on CTCs. 13 In the current study, we also found that megakaryocytes were more common in patients with carcinoma than in healthy volunteers. Many of the megakaryocytes appeared to have lost their cytoplasm.…”

“…A study of patients with pancreatic tumours found that no circulating epithelioid cells (cells resembling epithelial cells on cytology) were identified among nine normal healthy controls. Of the 115 patients with circulating epithelioid cells, 25 had nonmalignant disease and 90 had malignancy.…”

Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas

“…However, this has to be taken with a grain of salt, since this cannot be assigned to all tumor entities. For example, screening for pancreatic ductal adenocarcinoma (PDAC) by liquid biopsy has low specificity due to the fact that other non-malignant diseases of the pancreas like chronic pancreatitis can lead to high rates of false positive epithelial cell numbers in the blood [8,9].…”

Cytokeratin-positive cells in the bone marrow from patients with pancreatic, periampullary malignancy and benign pancreatic disease show no prognostic information

“…Also one of the PCR-based studies report a rate of 11% in cases with benign pancreatic disease, while reporting only one positive case in 20 healthy controls (30). In addition, there is one report disclosing the presence of epithelal cells in the bloodstream of patients with benign pancreatic disease (31). These cells could potentially enter the bone marrow via the bloodstream and could thereby be detected in BM-samples as well.…”