Diagnostic utility of cytologic sampling for main pancreatic duct abnormalities: A decade of institutional experience

Background Pancreatic duct abnormalities may be the only imaging manifestation of neoplasia, but the diagnostic utility of duct cytology is unclear. The objective of this study was to evaluate cytology in relation to duct diameter, ancillary studies, and histologic follow‐up. Methods The authors retrospectively analyzed 158 pancreatic duct cytology specimens from 144 patients obtained during 2014–2024. Main duct dilatation (MDD) was stratified by diameter. Cytologic diagnosis, fluid biochemistry, next‐generation sequencing (NGS), and cytology–histology correlation were assessed. Results Of 158 specimens, 145 (91.8%) had MDD, and 13 (8.2%) had stricture/stenosis. Sampling comprised 133 fine‐needle aspirations (84.2%) and 25 brushings (15.8%). In total, 98 specimens (62.0%) were nondiagnostic or negative. Cytologic diagnosis distributions did not differ among MDD groups ( p = .316). Carcinoembryonic antigen (CEA) was available for 93 specimens; 20 (21.5%) exceeded 192 ng/mL, including nine with nondiagnostic or atypical cytology. Of 60 specimens with interpretable NGS, 31 (51.7%) had mucinous‐associated mutations, and nine (15.0%) had high‐risk alterations. Histology was available for 51 patients; all 14 patients with neoplastic–other cytology had confirmed neoplasms. Adenocarcinoma was identified in 14 patients: one of 10 was nondiagnostic, four of seven were atypical, two of 14 were neoplastic–other, one of two was suspicious, and six of seven were positive. Cytology alone (neoplastic–other or worse) was 64.7% sensitive and 94.1% specific for neoplasia; adding available CEA and then NGS increased sensitivity to 73.5% and 91.2%, respectively, with 88.2% specificity. Conclusions Pancreatic duct cytology was highly specific but only moderately sensitive for neoplasia and did not differ by MDD severity. Although there was a modest decrease in specificity, CEA and NGS substantially improved sensitivity, supporting their adjunctive value in cytologically indeterminate cases.