Atypical cells in fine needle aspiration biopsies of pancreas: Causes, work-up, and recommendations for management.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a sensitive and specific method for diagnosing cancer in solid pancreatic masses. However, some cases receive indeterminate atypical diagnoses, which creates management dilemmas. In the 2014 Papanicolaou Society of Cytopathology (PSC) standardized guidelines for pancreatobiliary cytology, specimens in the "Atypical" category show a spectrum of architectural and/or cellular changes beyond normal or reactive, but, quantitatively or qualitatively, insufficient for classification as neoplastic (benign/other), suspicious or positive for malignancy. Implementation of the PSC system decreased atypical diagnoses, particularly for cystic lesions, and redistributed many cases into benign and neoplastic categories. Because no set cytologic criteria exist for the "Atypical" category there is wide variability in its use, and its frequency ranges from 0%-16% (mean 6%). It consists of a heterogeneous mix of cases that occur because of preanalytic, lesion-specific (low cellularity, necrosis, cystic, reactive and premalignant changes), to pathologist-dependent factors (experience, expertise, training and institutional case volume). Outcomes of atypical diagnoses in solid pancreatic masses range from benign to premalignant and malignant and include reactive atypia in pancreatitis, well differentiated adenocarcinoma, and non-ductal malignancies. The associated risk of malignancy (ROM) ranges from 28%-100%, with an overall intermediate ROM in large-scale studies. Cytopathologists and institutions should monitor and keep their personal and/or laboratory's atypical rates low by judiciously using rapid onsite evaluation, ancillary studies, consensus or expert review, as well as correlation with clinical and radiologic findings. Early repeat EUS-FNA is indicated for unresolved cases.