Elevating pancreatic cystic lesion stratification: Current and future pancreatic cancer biomarker(s)

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an incredibly deadly disease with a 5-year survival rate of 9%. The presence of pancreatic cystic lesions (PCLs) confers an increased likelihood of future pancreatic cancer in patients placing them in a high-risk category. Discerning concurrent malignancy and risk of future PCL progression to cancer must be carefully and accurately determined to improve survival outcomes and avoid unnecessary morbidity of pancreatic resection. Unfortunately, current image-based guidelines are inadequate to distinguish benign from malignant lesions. There continues to be a need for accurate molecular and imaging biomarker(s) capable of identifying malignant PCLs and predicting the malignant potential of PCLs to enable risk stratification and effective intervention management. This review provides an update on the current status of biomarkers from pancreatic cystic fluid, pancreatic juice, and seromic molecular analyses and discusses the potential of radiomics for differentiating PCLs harboring cancer from those that do not.

Keywords: Biomarker; Early detection; IPMN; Pancreatic cancer; Pancreatic cystic lesions; Pancreatic ductal adenocarcinoma; Radiomics.

Fig. 1.

Chart depiction of pancreatic cystic lesions (PCLs) types. All PCLs are divided into three main types, inflammatory, serous and mucinous. Those grouped under the “Other” heading are rare cyst types that include pseudopapillary tumors (SPT), lymphoendothelial cysts (LEC), and pancreatic neuroendocrine neoplasia (PNEN). The inflammatory type is predominately comprised of pseudocysts. Importantly, serous type cysts are rarely malignant. Mucinous cysts, however, divided into intraductal pancreatic mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN), harbor a greater potential for malignancy. Thus, this is the primary PCL population that undergoes surgical resection. The prevalence of IPMN types (branch, main, and mixed duct), as well as sub-classifications (gastric, intestinal, pancreaticobiliary, and oncocytic), are shown along with their respective proportions that harbor concurrent malignancy.

Fig. 2.

MRIs, gross images, and histology of various cystic lesion types resected from patients. The left column has serous cystic neoplasm (SCN) examples. A characteristic stellate scar is appreciated on the MRI and the gross specimen demarcated by red arrows. SCN histology is characterized by the presence of simple cuboidal epithelial cells with clear cytoplasm. The middle column has mucinous cystic neoplasm (MCN) examples. The MRI of an MCN is demarcated by a red arrow that is septated (small arrowheads) and contains an enhanced mural nodule (large arrowhead). The gross specimen contains a large septated lesion with a thick-walled pseudocapsule. Typical MCN histologic presentation with dense ovarian type stroma and epithelial cells lining the cyst that form papillae. The right column has examples of intraductal papillary mucinous neoplasms (IPMNs). Dilation of the main pancreatic duct is appreciated on MRI as demarcated by red arrows. The image of a gross IPMN specimen shows communication between the main pancreatic duct (arrowheads) and the solid/papillary lesion (arrow). Histologic presentation is typical of IPMNs with large papillary structures lined by epithelial cells harboring various degrees of atypia. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)