Spatial-Domain Low-Coherence Quantitative Phase Microscopy to Improve the Cytological Diagnosis of Pancreatic Cancer

Abstract

Use of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytology to detect pancreatic cancer is limited, with a high false negative rate mainly due to the relatively fewer number of completely cancerous cells. To improve the accuracy of EUS-FNA cytological diagnosis, we evaluated a novel optical system—spatial-domain low-coherence quantitative phase microscopy (SL-QPM)—to analyze nanoscale nuclear architecture on original cytology samples, especially those diagnosed as indeterminate for malignancy, with the goal of maintaining high specificity and reducing false positive rate. We performed SL-QPM on original cytology samples obtained by EUS-FNA from 40 patients with suspicious pancreatic solid lesions (27 adenocarcinomas, 5 neuroendocrine tumor, 8 chronic pancreatitis), including 13 cases that were cytologically indeterminate. Each diagnosis had been confirmed by follow-up surgical pathology. The SL-QPM-derived nanoscale nuclear architectural parameters distinguished pancreatic cancer from cytologically indeterminate cells. A logistic regression model using nuclear entropy and SD increased the sensitivity of cytology in identifying pancreatic cancer from 72% to 94% while maintaining 100% specificity. The SL-QPM-derived nanoscale nuclear architecture properties show great promise in improving the cytological diagnosis of EUS-FNA for pancreatic cancer and could be used when traditional cytopathology does not get an accurate diagnosis, and can be easily translated into a traditional clinical device.