Background Pancreatic ductal adenocarcinoma (PDAC) represents the most common primary pancreatic malignancy. An understanding of the cytomorphologic features of conventional ductal adenocarcinoma and its variants is important to ensure accurate diagnoses. Methods The clinicopathological and cytological data of serous fluids in PDAC patients were obtained from the electronic medical records and pathology database. All samples were analyzed and reclassified according to the “The International System for Reporting Serous Fluid Cytopathology” guidelines. Cytomorphologic features were examined with SurePath automatically prepared slides and stained using the Pap method in malignant (MAL) effusion specimens from 21 patients with PDAC. Immunocytochemical staining was conducted on 12 cell blocks from MAL PDAC effusion. Results A total of 137 serous fluids specimens of PDACs were included, among which 61 (44.5%), 9 (6.6%), 13 (9.5%), 52 (38.0%), and 2 (1.5%) patients were classified into malignancy, suspicious for malignancy, atypia of undetermined significance, negative for malignancy and nondiagnostic groups, respectively. The key cytologic features for the conventional type of PDAC included cohesive clusters of ductal cells in glandular crowding and disorganized “drunken honeycomb” pattern or intercalated duct‐like structure with anisonucleosis, cytoplasmic vacuoles, and concomitant “Indian‐file” configuration. Undifferentiated carcinoma was comprised of enlarged, undifferentiated, pleomorphic MAL cells. Adenosquamous carcinoma could show glandular and/or squamous differentiation. Colloid carcinoma was composed of three‐dimensional cancer cell clusters floating in thick mucin. Conclusion Crowding and disorganized “drunken honeycomb” pattern or intercalated duct‐like structure with anisonucleosis, may represent an important clue for diagnosing PDAC in serous fluids. Immunocytochemical staining in combination with review of medical records and cytomorphological data can serve as useful adjuncts for distinguishing between PDAC and its variants.
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