Cytology of cystic lesions of the pancreas: Practical insights, pearls, and pitfalls

Abstract Pancreatic cyst fluid (PCF) specimens present significant interpretive challenges. Accurate preoperative diagnosis is essential for guiding patient management, as pancreatic cysts vary from benign to pre‐malignant and malignant. Appropriate triage differentiates low‐risk cysts requiring surveillance from high‐risk cysts necessitating surgical resection, the latter of which have increased likelihood of progressing to or harboring invasive carcinoma. Optimal PCF assessment integrates radiological, cytological, biochemical, and molecular findings if available. Key biochemical markers such as carcinoembryonic antigen and glucose can improve the detection of neoplastic mucinous cysts. However, cytology remains the most specific modality for identifying high‐risk cysts. Cytomorphologic interpretation is particularly challenging due to the scant cellularity and degenerative changes often present in these specimens. This review provides practical insights to improve the evaluation of pancreatic cysts, emphasizing the importance of a multidisciplinary approach and highlighting diagnostic pearls and common pitfalls to aid in accurate interpretation and optimal patient care.