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

Abstract

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.

Diagnostic Performance of Pancreatic Cytology with the Papanicolaou Society of Cytopathology System: A Systematic Review, before Shifting into the Upcoming WHO International System

“…Our study found the ROM of the "atypical" category ranged from 28 to 100%. Reporting under this category has been linked with significant interobserver variability; while reasons for an "atypical" interpretation include sample degeneration, limited cellularity, prominent reactive or dysplastic changes, gastrointestinal contamination, or inexperience of the pathologist [33]. Rapid on-site evaluation (ROSE) could reduce sampling artifacts during EUS-FNA [34].…”

“…However, it seems to be of reduced value in pancreatic cystic lesions [35]. Reduction in "atypical" interpretations could be reached by applying ancillary techniques like immunohistochemistry or next-generation sequencing, asking help from experts, or performing a repeat FNA [33,[36][37][38].…”

Liquid-based cytology features of pancreatic acinar cell carcinoma: comparison with other non-ductal neoplasms of the pancreas

“…There are situations where reactive acini in pancreatitis could be misinterpreted as acinar cell neoplasia on cytology specimens [ 12 , 21 ]. HooKim et al [ 5 ] demonstrated that the presence of syncytial clusters, prominent cherry red nucleoli and necrosis could be useful clues for the distinction between reactive pancreatic acini and ACC. ACC may show overlapping cytologic features with intraductal oncocytic papillary neoplasm; however, ACC is more mitotically active, and demonstrates a necrotic background [ 22 ].…”

“…Endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) is a well-established diagnostic method for solid pancreatic tumors, and thus an accurate diagnosis on aspiration cytology material is essential to guide the next steps for patient management [ 4 , 5 ]. While conventional smear (CS) cytology was the standard method for processing EUS-FNA cytology specimens, CS preparations often result in bloody smears, dry artifacts, and crushing artifacts, which could obscure the cytologic features and result in a suboptimal diagnosis [ 6 ].…”