EUS-Anchored Multimodal Evaluation of Pancreatic Cystic Lesions: Toward a Conceptual Diagnostic Framework
Abstract
1. Background
2. Overview of Pancreatic Cystic Lesions
3. Comprehensive EUS Evaluation of Pancreatic Cystic Lesions
3.1. Morphological Evaluation of PCLs
3.2. Functional Evaluation of PCLs
3.3. EUS-Guided Tissue and Fluid Acquisition
4. Molecular Profiling and Biomarker Characterization of Pancreatic Cystic Lesions
4.1. Conventional Biochemical Biomarkers
4.1.1. CEA
4.1.2. Cyst-Fluid Glucose
4.1.3. Cyst-Fluid Amylase
4.2. Cyst-Fluid Biomarkers with Potential Clinical Application Value
4.2.1. Mucin-Related Glycoproteins
4.2.2. CA19-9
4.2.3. VEGF-A
4.3. Emerging Genetic Molecular Testing
4.3.1. Diagnostic Mutations for Cyst Typing
4.3.2. NGS-Based Platforms
4.3.3. Liquid-Biopsy Markers
5. Artificial Intelligence in the Assessment of PCLs
5.1. Imaging-Based Artificial Intelligence for PCL Evaluation
5.2. AI-Assisted Analysis of Biomarkers and Molecular Profiles in PCLs
5.2.1. AI in Biochemical Biomarker Evaluation
5.2.2. AI in Emerging Molecular and Genomic Biomarker Analysis
6. Multi-Model Approach for Risk Stratification and Personalized Evaluation of PCLs
7. Summary and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
| PCLs | Pancreatic Cystic Lesions |
| EUS | Endoscopic Ultrasound |
| AI | Artificial Intelligence |
| CT | Computed Tomography |
| MRI | Magnetic Resonance Imaging |
| IPMNs | Intraductal Papillary Mucinous Neoplasms |
| MCNs | Mucinous Cystic Neoplasms |
| SCNs | Serous Cystic Neoplasms |
| SPNs | Solid Pseudopapillary Neoplasms |
| cNETs | cystic Neuroendocrine Tumors |
| CE-EUS | Contrast-Enhanced EUS |
| EUS-FNA | EUS-guided Fine-needle Aspiration |
| EUS-FNB | EUS-guided Fine-needle Biopsy |
| EUS-TTNB | EUS through-the-needle micro-forceps Biopsy |
| CEA | Carcinoembryonic Antigen |
| MUC | Mucin-related glycoprotein |
| VEGF | Vascular Endothelial Growth Factor |
| NGS | Next-generation Sequencing |
| HGD | High-grade Dysplasia |
| IC | Invasive Cancer |
| cfDNA | cell-free DNA |
| miRNA | microRNA |
| CNNs | Convolutional Neural Networks |
| AUC | Area Under the curve |
| XAI | Explainable AI |
| ML | Machine Learning |
| SVM | Support Vector Machine |
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| Technique | Target Parameter | Imaging and Sampling Findings | Diagnostic and Risk-Stratification Value | Strengths | Limitations |
|---|---|---|---|---|---|
| Conventional EUS morphology | Cyst structure; ductal anatomy | Multilocularity; wall thickening; mural nodules; MPD dilation; ductal communication | Lesion characterization; identification of worrisome features (e.g., mural nodules, ductal dilation) | High-resolution imaging; real-time assessment | Operator dependence; limited specificity in overlapping features |
| CE-EUS | Vascularity of mural nodules and cyst wall | Hyper-enhancing mural nodules; non-enhancing intracystic material | Differentiation of vascularized neoplastic tissue from avascular intracystic content | Microvascular visualization; contrast-enhanced characterization | Requirement for contrast agents; operator dependence |
| EUS elastography | Tissue stiffness | Increased stiffness (hard pattern); soft pattern | Adjunctive assessment of tissue composition (fibrotic or neoplastic vs. non-neoplastic) | Noninvasive stiffness assessment; functional tissue characterization | Limited standardization; adjunctive diagnostic role |
| EUS-FNA | Cyst fluid | Low cellularity aspirate; fluid biomarkers | Mucinous cyst identification; cytologic confirmation of malignancy when positive | Wide availability; fluid-based biochemical and molecular analysis | Low cellularity; limited sensitivity; false-negative cytology |
| EUS-FNB | Cyst wall; mural nodules; solid components | Core tissue with preserved architecture | Histologic diagnosis in lesions with mural nodules or solid components | Core tissue acquisition; preservation of histologic architecture | Limited utility in purely cystic lesions; technical dependence |
| EUS-TTNB | Intracystic wall; septa; epithelium | Direct epithelial tissue sampling | Histologic characterization of cyst epithelium; cyst subtype classification | Direct epithelial sampling; improved histologic yield | Procedure-related adverse events; technical complexity |
| Features | BD-IPMNs | MD-IPMNs or MT-IPMNs | MCNs | SCNs | cNETs | SPNs |
|---|---|---|---|---|---|---|
| Age (years) | 50–70 | 50–70 | 30–50 | 60–80 | 50–60 | 20–40 |
| Gender | F = M | F = M | F (>95%) | F (70%) | M > F | F (>80%) |
| Location in pancreas | 50% in head and uncinate | Any | 90% in body and tail | Any | Any | Any |
| Clinical symptoms | Mostly no symptom when lesions are small | Mostly no symptom when lesions are small | Up to 50% of cases (might associate with compressive symptoms) | Up to 50% of cases (might associate compressive symptoms) | 90% asymptomatic. Functional symptoms (depend on secreted hormone) | Mostly no. Abdominal pain or discomfort (37%) |
| Calcification | No | No | Rare peripheral calcification | Central calcification in 30–40% | No | Irregular |
| Malignant potential | Yes | Yes | Yes | None | Irregular | Irregular |
| Glucose | Low | Low | Low | Normal | - | - |
| Amylase (U/L) | >250 | >250 | <250 | <250 | - | >250 |
| CEA (ng/mL) | >192 | >192 | >192 | <5 | <5 | <5 |
| KRAS mutation | Yes | Yes | Yes | Very rare | None | |
| GNAS mutation | - | Yes | Yes | - | - | - |
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© 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.
Share and Cite
Liu, E.; Yang, F. EUS-Anchored Multimodal Evaluation of Pancreatic Cystic Lesions: Toward a Conceptual Diagnostic Framework. J. Clin. Med. 2026, 15, 3893. https://doi.org/10.3390/jcm15103893
Liu E, Yang F. EUS-Anchored Multimodal Evaluation of Pancreatic Cystic Lesions: Toward a Conceptual Diagnostic Framework. Journal of Clinical Medicine. 2026; 15(10):3893. https://doi.org/10.3390/jcm15103893
Chicago/Turabian StyleLiu, Enshuo, and Fei Yang. 2026. "EUS-Anchored Multimodal Evaluation of Pancreatic Cystic Lesions: Toward a Conceptual Diagnostic Framework" Journal of Clinical Medicine 15, no. 10: 3893. https://doi.org/10.3390/jcm15103893
APA StyleLiu, E., & Yang, F. (2026). EUS-Anchored Multimodal Evaluation of Pancreatic Cystic Lesions: Toward a Conceptual Diagnostic Framework. Journal of Clinical Medicine, 15(10), 3893. https://doi.org/10.3390/jcm15103893

