Molecular analysis of cyst fluids improves the diagnostic accuracy of pre-operative assessment of pancreatic cystic lesions

Abstract

Pancreatic cystic lesions (PCL) are increasingly diagnosed. Endoscopic ultrasound fine-needle aspiration (EUS-FNA) cytology is often used for diagnostic confirmation but can be inconclusive. In this study, the role of molecular analyses in the pre-operative diagnostics of PCL is evaluated. Targeted Next Generation Sequencing (NGS) applied on cytology smears was retrospectively evaluated in a cohort of 37 resected PCL. Usefulness of NGS on fresh cyst fluids was tested in a prospective cohort of patients with newly diagnosed PCL (n = 71). In the retrospective cohort, cytology plus NGS displayed higher sensitivity (94.1% vs. 87.1%) and specificity (100% vs. 50%) than cytology alone for the detection of mucinous neoplasms. In the prospective cohort, sensitivity and specificity of conventional cytology alone were 54.2% and 100% for the detection of mucinous neoplasia and 50.0% and 100% for the detection of high-grade dysplasia, respectively. Adding NGS, all lesions which underwent histopathologic verification (12/71, 17%) could be classified without false positive or false negative results regarding the detection of mucinous neoplasm so far. NGS analysis of cfDNA in PCL fluids is feasible and can increase diagnostic accuracy in the detection of mucinous neoplasms compared to cytology alone. However, algorithms for the detection of high-risk lesions need further improvement.

Single‐Molecule Bioelectronic Label‐Free Assay of both Protein and Genomic Markers of Pancreatic Mucinous Cysts’ in Whole Blood Serum

“…However, the diagnostic sensitivity in detecting high-grade cysts that should immediately undergo resection, remains relatively low (77%). [12] A valid approach to improve the diagnostic sensitivity of high-grade mucinous lesions, enabling a quick diagnostic statement, is to tackle several biomarkers simultaneously. Relevantly they should all be detected with the lowest possible limit-of-detection [13] as they are not present in a normal cell population.…”

“…However, the diagnostic sensitivity in detecting high‐grade cysts that should immediately undergo resection, remains relatively low (77%). [ 12 ]…”

The Yield of String Sign in Differentiating Mucinous from Non-Mucinous Pancreatic Cysts: A Retrospective Cross-Sectional Study

“…Recently, molecular and liquid sample analysis has been reported to improve the diagnostic yield of mucinous pancreatic cysts with potentially high-grade lesions, however, the experience with these tests is still limited, as they are not easily available at every center, are time consuming, and require resources [ 24 ]. Whereas use of the string sign is a simple, bedside, cost-free test providing an immediate diagnosis.…”

Management of pancreatic cysts and guidelines: what the gastroenterologist needs to know

“… 93 , 94 Additional mutations ( TP53 , SMAD4 , PIK3CA , PTEN , CDKN2A ) have been shown to be associated with preoperative risks for advanced neoplasia in mucinous cysts, but need validation in multicenter studies. 93 , 95 – 98 …”

“…93,94 Additional mutations (TP53, SMAD4, PIK3CA, PTEN, CDKN2A) have been shown to be associated with preoperative risks for advanced neoplasia in mucinous cysts, but need validation in multicenter studies. 93,[95][96][97][98] Cyst fluid glucose level: Multiple studies have shown glucose levels to be lower in mucinous compared with non-mucinous PCNs. 24,99,100 For example, a meta-analysis of eight studies including 609 PCNs found that when PCN fluid glucose was compared with PCN fluid CEA, glucose had a higher sensitivity (91% versus 56%) and diagnostic accuracy for detecting mucinous lesions (94% versus 85%), with no difference in specificity between the tests.…”