Xanthogranulomatous cholecystitis: a premalignant condition?

Abstract

Xanthogranulomatous cholecystitis (XGC) is an uncommon variant of chronic cholecystitis, characterized by marked thickening of the gallbladder wall and dense local adhesions. It often mimics a gallbladder carcinoma (GBC), and may coexist with GBC, leading to a diagnostic dilemma. Furthermore, the premalignant nature of this entity is not known. This study was undertaken to assess the p53, PCNA and beta-catenin expression in XGC in comparison to GBC and chronic inflammation. Sections from paraffin-embedded blocks of surgically resected specimens of GBC (69 cases), XGC (65), chronic cholecystitis (18) and control gallbladder (10) were stained with the monoclonal antibodies to p53 and PCNA, and a polyclonal antibody to beta-catenin. p53 expression was scored as the percentage of nuclei stained. PCNA expression was scored as the product of the percentage of nuclei stained and the intensity of the staining (1-3). A cut-off value of 80 for this score was taken as a positive result. Beta-catenin expression was scored as type of expression-membranous, cytoplasmic or nuclear staining. p53 mutation was positive in 52% of GBC cases and 3% of XGC, but was not expressed in chronic cholecystitis and control gallbladders. p53 expression was lower in XGC than in GBC (P<0.0001). PCNA expression was seen in 65% of GBC cases and 11% of XGC, but not in chronic cholecystitis and control gallbladders. PCNA expression was higher in GBC than XGC (P=0.0001), but there was no significant difference between the XGC, chronic cholecystitis and control gallbladder groups. Beta-catenin expression was positive in the GBC, XGC, chronic cholecystitis and control gallbladder groups. But the expression pattern in XGC, chronic cholecystitis and control gallbladders was homogenously membranous, whereas in GBC the membranous expression pattern was altered to cytoplasmic and nuclear. The expression of p53, PCNA and beta-catenin in XGC was significantly different from GBC and similar to chronic cholecystitis, thus indicating the inflammatory nature of XGC and may not support a premalignant nature of the lesion.