Diagnostic spectrum and cytomorphological features of 1,641 pancreatobiliary EUS-FNA specimens: a five-year retrospective study from a central cytopathology laboratory serving 14 hospitals

Background and aim Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a well-established minimally invasive method for evaluating pancreatic and biliary tract lesions. Cytological assessment of EUS-FNA samples provides information on the heterogeneous spectrum of pancreatobiliary diseases. This study aimed to describe the real-world diagnostic spectrum, cytomorphological characteristics, specimen adequacy, and distribution of cytological diagnostic categories in pancreatobiliary EUS-FNA specimens obtained in routine clinical practice. Methods This retrospective real-world diagnostic spectrum study analyzed 1,641 EUS-FNA specimens obtained from pancreatic and biliary tract lesions between January 2021 and November 2025. Specimens were obtained from EUS-FNA procedures performed at 14 referring hospitals across Germany and interpreted at a single central reference cytopathology laboratory. Specimens were processed using conventional May–Grünwald–Giemsa and Papanicolaou staining, and cytological diagnoses were categorized following systematic cytomorphological evaluation with integration of available clinical and radiological information. The primary study outcomes were the distribution of cytological diagnoses, specimen adequacy, non-diagnostic rates, and the cytomorphological spectrum of pancreatobiliary lesions. Because systematic histopathological or long-term clinical reference-standard follow-up was not available for the entire cohort, formal diagnostic performance analyses were not performed. Results Definitive cytological diagnoses were obtained in 503 cases (30.7%). Non-diagnostic specimens accounted for 133 of 1,641 cases (8.1%), corresponding to a diagnostic yield of 91.9% (1,508/1,641) when all other categories were counted as clinically informative. Pancreatic ductal adenocarcinoma was the most common diagnosis ( n = 291; 17.7%), followed by pancreatic neuroendocrine neoplasms ( n = 51; 3.1%), neuroendocrine carcinoma ( n = 11; 0.7%), acinar cell carcinoma ( n = 10; 0.6%), solid pseudopapillary neoplasm ( n = 6; 0.4%), adenosquamous carcinoma ( n = 2; 0.1%), and mucinous neoplasms including cystadenocarcinoma ( n = 1; 0.1%). Benign and premalignant cystic lesions included pseudocysts ( n = 79; 4.8%), intraductal papillary mucinous neoplasms ( n = 36; 2.2%), and serous cystadenomas ( n = 3; 0.2%). Other findings comprised metastatic tumors ( n = 34; 2.1%), malignant tumors not otherwise specified ( n = 47; 2.9%), suspicious for malignancy ( n = 115; 7.0%), inflammatory lesions ( n = 149; 9.1%), negative/normal cytology ( n = 558; 34.0%), and non-diagnostic samples ( n = 133; 8.1%). Conclusion EUS-FNA cytology provides clinically relevant information across a wide range of pancreatic and biliary tract lesions. This large, real-world cohort delineates the contemporary diagnostic spectrum of pancreatobiliary EUS-FNA cytology encountered in routine clinical practice and provides reference data on the distribution of cytological diagnostic categories, with a supplementary reclassification according to the WHO International System for Reporting Pancreaticobiliary Cytopathology. These data may serve as reference values for institutional quality assurance, including the monitoring of diagnostic yield and non-diagnostic rates.