Peripheral vascular rim on endoscopic ultrasound as a practical rule-in sign for pancreatic neuroendocrine neoplasms

Detection of a pancreatic mass is often anxiety-provoking for both patients and clinicians. This anxiety is largely driven by the poor prognosis associated with pancreatic ductal adenocarcinoma (PDAC), which continues to underlie a dismal 5-year survival rate despite advances in oncologic care.1 PDAC is the most common type of pancreatic cancer, accounting for approximately 90% of cases. Pancreatic neuroendocrine neoplasms (pNENs) are the second most common, accounting for approximately 1% to 5%.2 Because prognosis, biology, and treatment strategies differ substantially among pancreatic tumors, rapidly differentiating PDAC from other tumors, particularly pNEN, is essential whenever a pancreatic mass is identified.

In current practice, contrast-enhanced computed tomography (CT) is typically the first-line imaging modality for evaluating pancreatic masses. However, differential diagnosis between PDAC and pNEN via CT alone remains challenging, particularly in small lesions or cases with atypical enhancement patterns.3 Endoscopic ultrasound (EUS) has emerged as a central modality for evaluating pancreatic masses due to its superior lesion detection sensitivity, especially for small pancreatic tumors.4,5 EUS also enables tissue acquisition, and histological confirmation remains the gold standard.4,5

Careful EUS-based morphological assessment prior to biopsy plays a critical role in guiding clinical suspicion and procedural planning. This is particularly relevant when tissue acquisition is not feasible, such as in lesions located in technically challenging locations or in patients with increased bleeding risk due to hematologic disorders or ongoing anticoagulation therapy.6 In such cases, the ability to extract meaningful diagnostic information from EUS imaging alone becomes especially important.

Several adjunctive EUS techniques have been developed to improve lesion characterization. Among these, elastography and contrast-enhanced EUS (CE-EUS) are the most thoroughly studied. Elastography provides information on tissue stiffness and may help differentiate malignant from benign lesions.7 To date, its availability depends on platform-specific hardware and software, and result interpretation remains operator-dependent. In contrast, CE-EUS enables real-time assessment of microvascular perfusion and has shown high diagnostic utility for differentiating hypervascular pNEN from hypovascular PDAC.8 At present, commonly used second-generation contrast agents are not universally available, and CE-EUS requires intravenous contrast administration, dedicated contrast-specific imaging settings, and additional observation time for dynamic-phase assessments.

In contrast, Doppler-based assessments are universally available on virtually all EUS platforms and do not require additional equipment or contrast agents. Despite its simplicity, Doppler imaging has been underutilized for detailed vascular characterization and its use is often limited to identification of major vessels rather than elucidation of subtle microvascular patterns.

Amaya-Fragoso et al.9 introduced the peripheral vascular rim (PVR) observed on EUS Doppler as a novel and highly specific imaging feature associated with pNEN. The authors demonstrate that PVR is exclusively observed in pNEN and achieves 100% specificity for histopathological diagnosis, thereby supporting its role as a practical rule-in sign. Notably, this finding can be obtained using standard power Doppler imaging without contrast enhancement or additional procedural time, thereby highlighting its potential applicability in routine clinical practice. In their study of 125 solid pancreatic lesions (43 pNEN and 82 PDAC), hypervascularity was far more common in pNEN than in PDAC (46.5% vs. 1.2%). A PVR was identified in 34.9% of pNENs and 0% of PDACs. Pancreatic atrophy, pancreatic duct dilation, and vascular invasion are commonly associated with PDAC. Mean lesion size was approximately 40 mm, and subgroup analysis (<20 mm vs. >20 mm) showed that PVR remained exclusive to pNEN despite the limited number of small PDACs. In multivariate analysis, hypervascularity (odds ratio [OR], 3.8), PVR (OR, 2.8), and pancreatic atrophy (OR, 0.3) remained significant. From a diagnostic standpoint, PVR achieved 100% specificity and positive predictive value, but only 34.9% sensitivity, underscoring its role as a rule-in rather than a rule-out sign.

Beyond its diagnostic performance, PVR is particularly intriguing because it reflects the presence of vascularity and its spatial distribution. This pattern may correspond to the underlying tumor biology of pNEN, which is characterized by a rich and organized microvascular network.10 In contrast, PDAC is typically associated with desmoplastic stroma and relatively poor vascularization.3 Identification of a circumferential vascular signal surrounding the lesion may thus provide biologically meaningful information that extends beyond conventional morphological assessment.

This observation aligns with the evolving role of EUS as a modality integrating structural and functional imaging. While CE-EUS represents a more advanced approach to perfusion assessment,8 the present study suggests that even basic Doppler techniques can capture clinically relevant microvascular features when interpreted with attention to specific patterns. In this regard, PVR may serve as a simplified surrogate marker of vascular architecture, bridging the gap between conventional EUS and advanced imaging techniques.

This study has several limitations. PVR offers limited sensitivity, and its absence does not exclude a diagnosis of pNEN. Vascular patterns may vary according to tumor size, grade, and technical factors affecting Doppler signal acquisition. Our study’s retrospective single-center design also raises the possibility of selection bias and limits the generalizability of our findings. Interobserver variability and lack of standardized criteria for PVR assessment warrant further investigation.

PVR should not be regarded as a substitute for tissue acquisition. EUS-guided biopsy remains the reference standard for diagnosis and grading, particularly given its implications for treatment selection.3,5,6 Instead, PVR may function as a complementary imaging marker that enhances diagnostic confidence, especially in cases where biopsy is not feasible or yields inconclusive results.

From a broader perspective, this study highlights a pragmatic balance between advanced imaging technologies and real-world applications. Although CE-EUS can provide detailed characterization of tumor perfusion, Doppler-based assessment offers a universally accessible and cost-neutral alternative that can inform clinical decision-making. Such simple and reproducible imaging features may confer a meaningful clinical impact in routine practice. Future prospective multicenter studies with standardized imaging protocols are warranted to validate these findings and define their role in multimodal diagnostic algorithms for pancreatic lesions.