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Background Patients with xanthogranulomatous cholecystitis sometimes exhibit imaging and intraoperative findings that are similar to those of advanced gallbladder cancer,thus these patients are easily misdiagnosed.The present study aimed to investigate the characteristics of xanthogranulomatous cholecystitis masquerading as gallbladder cancer that could potentially aid in the correct diagnosis of this condition.Methods The clinical,serological,radiological and operative features of twelve patients with obviously wall-thickening or mass-forming xanthogranulomatous cholecystitis were retrospectively analyzed.Additionally,the patient preoperative features were compared to those of 36 patients with advanced gallbladder cancers.Results Twelve patients with xanthogranulomatous cholecystitis exhibited one to three episodes of acute cholecystitis within 0.5 to 7 months prior to admission to the hospital.Five of these patients exhibited concomitant choledocholithiasis,whereas no concomitant choledocholithiasis was identified in patients with advanced gallbladder cancer.The incidence of abdominal pain (x2=6.588,P=0.010),acute cholecystitis (x2=29.176,P=0.000),acute cholangitis (x2=6.349,P=0.012),choledocholithiasis (x2=16.744,P=0.000),carcinoembryonic antigen test (P=0.007),CA125 (P=0.001),and diffuse gallbladder wall thickening (x2=6.031,P=0.014),continued mucosal line (x2=15.745,P=0.000),homogeneous enhancement of mucosal line (x2=19.947,P=0.000),submucosal hypoattenuated nodules or band (x2=18.607,P=0.000) in computed tomography demonstrated statistically significant differences between cases of xanthogranulomatous cholecystitis and gallbladder cancer.Furthermore,all the twelve patients with xanthogranulomatous cholecystitis exhibited at least one positive computed tomography imaging feature aside from past acute cholecystitis episode,and no patient with advanced gallbladder cancer simultaneously exhibited past acute cholecystitis episode and at least one positive computed tomography imaging feature.Conclusions The accurate preoperative diagnosis of xanthogranulomatous cholecystitis includes an integrated review of past acute cholecystitis episode,choledocholithiasis,and positive computed tomography imaging features.Besides,we present an algorithm for intraoperative diagnosis.