Cystic tumors of the pancreas: Current perspectives on diagnosis and management

Abstract

Pancreatic cystic lesions are being increasingly detected, mainly due to the widespread use of cross-sectional imaging. The reported prevalence ranges from 13% to 18% in asymptomatic individuals. These lesions display a broad histologic spectrum, from benign pseudocysts to premalignant mucinous cystic neoplasms and invasive carcinomas. Although many classification and management strategies exist, the natural history of numerous pancreatic cystic lesions remains incompletely understood, contributing to significant clinical uncertainty. Current diagnostic tools, including computed tomography, magnetic resonance imaging, endoscopic ultrasound, and cyst fluid analysis, are constrained by either suboptimal sensitivity or high costs. Cytology, while specific when positive, suffers from low sensitivity. Biochemical markers such as carcinoembryonic antigen, amylase, and glucose can help in cyst differentiation, whereas molecular testing (e.g., KRAS, GNAS, RNF43 mutations) provides additional diagnostic and prognostic value. However, the application of molecular diagnostics is still restricted in routine practice due to costs, access issues, and a lack of standardization. This diagnostic uncertainty leads to both overtreatment and undertreatment. Some patients undergo unnecessary surgeries for benign lesions, which exposes them to procedural risks and long-term consequences. Others may experience delays in interventions for high-risk cysts and missing opportunities for cancer prevention. Additionally, prolonged, and often unnecessary surveillance burdens patients and healthcare systems psychologically and financially. In this minireview, we present a comprehensive overview of the classification, diagnostic approach, and management of pancreatic cystic lesions, incorporating recent evidence and current international guidelines (Fukuoka, American Gastroenterological Association, European). We also highlight the limitations of existing strategies and emerging tools such as radiomics, next-generation sequencing, and novel biomarkers. Additionally, we emphasize the urgent need for cost-effective, accurate, and accessible diagnostic pathways. A more refined risk stratification approach is essential to optimize outcomes, reduce healthcare waste, and improve the quality of life for patients with pancreatic cystic lesions.

Keywords: Pancreatic cystic lesions; Intraductal papillary mucinous neoplasm; Radiomics; Molecular diagnostics; Risk stratification; Artificial intelligence; Endoscopic ultrasound; Next-generation sequencing; Pancreatoscopy; Multidisciplinary management

Core Tip: Pancreatic cystic lesions are increasingly detected in clinical practice, yet their diagnosis and management remain challenging due to overlapping imaging features, variable malignant potential, and limitations in current diagnostic tools. This minireview provides an up-to-date overview of classification systems, diagnostic strategies, including imaging, cyst fluid analysis, and molecular testing, as well as international guideline recommendations. It also highlights emerging technologies such as radiomics and next-generation sequencing. Emphasis is placed on the urgent need for cost-effective, accurate, and patient-focused risk stratification models to guide personalized surveillance and therapeutic decisions.