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Endoscopic ultrasound tissue acquisition, in the form of fine needle biopsy (EUS-FNB) was designed to provide a proper quantitative sample for determining the histologic architecture and further immunohistochemical staining. This study aimed to investigate the contribution of associating contrast-enhanced ultrasound imaging (CEUS) with EUS-FNB for differentiating solid pancreatic lesions without on-site cytopathology. Patients from our institutional database who underwent CE-FNB-EUS for the evaluation of a solid pancreatic lesion were retrieved. Micro vascularization of the tumor was evaluated over 2 min during CEUS after intravenous injection of 4.8 mL SonoVue and was classified as hypervascular, isovascular or hypovascular during both arterial and venous phase. Final diagnosis was based on histopathology of surgical specimens or EUS-guided tissue acquisition and clinical follow-up. Our retrospective study (2018-2021) enrolled 46 patients with a mean age of 58, female to male ratio 1:2, mass location: 2/3 head, 1/3 body and tail of the pancreas, average mass size 3.5 cm, mean number of needle passes (fanning technique): 2. Final pathology revealed pancreatic ductal adenocarcinoma-PDAC (26), mass-forming pancreatitis-MFP (10), pancreatic neuroendocrine tumors-pNETs (4), undifferentiated carcinoma (3), mucinous carcinoma (1), pancreatic metastasis (1). Hypo-enhancement was noted in 67% of the patient, and the final diagnosis was malignancy in all those cases. Regarding the enhancement patterns: hypovascularity in both arterial and venous phase was associated to PDAC, hypervascularity or isovascularity in both phases were associated to either MFP or NETs, while the carcinomas were hypervascular. A heterogeneous appearance with non-enhancing areas was noted in a small percentage of the hypo-enhancing lesions and it might suggest necrosis. The overall diagnostic accuracy was 91%. CE-EUS allows detailed visualization of the dynamic enhancement patterns hence it helps to identify the target of EUS-FNB among different pathological areas of the lesions. CE-FNB-EUS can be used for the differential diagnosis and adequate sampling of solid pancreatic lesions without on-site cytopathology. [ABSTRACT FROM AUTHOR]