Xanthogranulomatous cholecystitis – A diagnostic challenge

An 80-year-old woman presented with a 2 weeks history of upper right quadrant abdominal pain. Physical exam revealed right hypochondrial tenderness. Admission blood tests showed leucocytosis (11.60x10^9/L) and elevated C-reactive protein (10,1 mg/dL), AST (254U/L), ALT (168U/L), g GT (314 U/L) and total bilirubin (3,67 mg/dL)

Ultrasonography showed a non-distended gallbladder (GB), with diffuse and irregular wall thickening, indistinctive from the adjacent liver parenchyma, containing heterogenous material, without lithiasis. Dilation of the intrahepatic biliary ducts was also present; common bile duct diameter was in the upper limit of normal.

MR cholangiopancreatography (MRCP) confirmed the marked diffuse and heterogenous GB wall thickening and heterogeneity of signal of the adjacent liver parenchyma, with restricted diffusion, namely at the confluence of the central biliary ducts with concomitant stenosis. Choledocholithiasis was absent. Hepatic capsular retraction and loss of fat planes between the GB and the hepatic colic flexure and the duodenum were also present.

Regarding the imaging, laboratory and clinical findings, GB cancer was the presumed diagnosis, leading to extended cholecystectomy. Adherence to the colon and liver was confirmed at surgery and pathology of both the extemporaneous and final specimens showed chronic xanthogranulomatous cholecystitis (XGC) infiltrating the hepatic parenchyma, without neoplastic cells.

XGC is an uncommon aggressive form of chronic cholecystitis that can mimic GB cancer. It most commonly affects 60-70-year-old women and clinical presentation is similar to other types of cholecystitis or carcinoma [1]. Histologically, besides an inflamed GB wall, there’s fibrosis and intramural xanthogranulomas [1,2].

Some radiologic features are helpful in favouring the preoperative diagnosis of XCG over carcinoma, as they reflect well the histopathologic findings [2,3,4]: diffusely thickened gallbladder wall enclosing hypoechoic/hypoattenuating/very high T2 signal intensity nodules; continuous mucosal enhancement; absence of intrahepatic bile duct dilation and of macroscopic hepatic invasion. Diagnostic performance increases significantly when a combination of at least three of these findings are present, with sensitivity, specificity and accuracy described as high as 83%, 100% and 91%, respectively [3]. On the other hand, the presence of macroscopic invasion of the liver bed, biliary obstruction and adenopathy favour GB carcinoma (but can be seen in XGC) [3,5]. Serum levels of CA 19-9 may be moderately elevated in cases of XGC, and previous studies have observed that they aren’t helpful to differentiate the two entities [6,7]. Although the coexistence of calculus as a differentiating sign remains under debate, the few studies comparing GB cancer with XGC have shown a stronger association with XGC [5,8]. Preoperative differentiation can be hampered when the destructive xanthogranulomatous process infiltrates adjacent organs and progresses with complications (GB perforation, fistula/abscess formation, biliary ductal obstruction/stricture, and ascending cholangitis), such as in our case; the patient’s age and several other signs also favoured the hypothesis of cancer over XGC: GB wall thickening was heterogeneous, affecting predominantly the fundus; mucosal enhancement could not be evaluated (due to significant wall thickening and absence of distention of the GB); infiltration of the adjacent liver parenchyma was present, as well as a biliary stenosis with intrahepatic bile duct dilation (both confirmed intraoperatively).

Cholecystectomy remains the treatment of choice, since histopathological confirmation is necessary to exclude cancer [9]. Preoperative fie needle aspiration cytology is recommended for suspected cases and meticulous gross observation during surgery along with several intraoperative frozen section examinations are necessary since the association of XGC and GB cancer occurs in around 10% of cases [5,10,11].

To conclude, XGC is an aggressive form of cholecystitis and the high frequency of complications reinforce the need for early suspicion at imaging. Nevertheless, diagnostic performance decreases significantly when severe inflammation is present or in the absence of at least three of the described imaging findings, precluding the accurate differentiation from GB cancer. The final diagnosis remains based on the histopathology findings.