Preoperative Diagnostic Challenges in Patients Being Evaluated for Resection of Pancreatic Serous Cystadenomas.

Serous cystadenomas (SCAs) are benign pancreatic cystic neoplasms for which surveillance can be safely discontinued once the diagnosis is established with confidence. However, distinguishing SCAs from premalignant or malignant pancreatic cystic lesions remains challenging despite advances in cross-sectional imaging and endoscopic ultrasound (EUS), resulting in unnecessary pancreatic resection. We performed a retrospective review of all pancreatic resections performed at a single tertiary referral center between January 2010 and December 2022 to identify patients with a final pathological diagnosis of SCA. Demographic, radiographic, operative, and postoperative outcomes were analyzed. Among 556 pancreatic resections, 20 patients (4%) had pathologically confirmed SCAs. The median age was 62 years, 55% were women, and the median cyst size was 3.0 cm. Surgery was performed because malignancy could not be excluded in 40% of patients, concern for a mucinous cystic neoplasm in 35%, and interval cyst growth in 25%. Sixteen patients (80%) underwent preoperative EUS with fine-needle aspiration, but cytology was frequently nondiagnostic and neither confirmed SCA nor reliably excluded a mucinous lesion. Seven patients underwent pancreaticoduodenectomy and 13 underwent distal pancreatectomy. Postoperative morbidity occurred in 50% of patients, including clinically relevant postoperative pancreatic fistula in 30%, with no disease-specific mortality. These findings demonstrate that pancreatic resection for SCAs is driven primarily by persistent diagnostic uncertainty rather than symptoms or malignant potential. Despite contemporary imaging and EUS, confidently differentiating SCAs from premalignant or malignant pancreatic cystic neoplasms remains difficult. Improved diagnostic strategies, including molecular testing and enhanced risk stratification, may reduce unnecessary pancreatic resection while preserving oncologic safety.