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Xanthogranulomatous cholecystitis (XGC) is a benign, uncommon variant of chronic cholecystitis characterised by focal or diffuse destructive inflammatory process of the gallbladder (GB). Macroscopically, it appears like yellowish tumour-like masses in the wall of the GB. This article reports on a 74-year-old woman with XGC mimicking GB cancer.
Xanthogranulomatous cholecystitis (XGC) is a rare, chronic granulomatous inflammation of the gallbladder (GB) first described by Christensen and Ishak1 in 1970 as ‘fibroxanthogranulomatous inflammation’ and later in 1976 as XGC by McCoy et al.2 It is believed to be a variant of chronic cholecystitis with invasive features to surrounding structures that can be destructive and cause significant morbidity. It is predominantly seen in the Japanese or South Asian population with age of presentation between 44 and 63 years.3 4 The prevalence ranges from 0.7% in the USA to 10% in India3 5–8 with no clear gender differences.3 4 8 9 It is usually difficult to clinically distinguish XGC from GB carcinoma due to their similar modes of presentation as shown in our case.
A 74-year-old Caucasian woman presented with painless obstructive jaundice. She had no history of GB disease, smoking or alcohol intake. She had no symptoms of fever, nausea, vomiting, abdominal pain, weight loss or changes in bowel habits. Physical examination revealed generalised icterus with excoriation marks. The abdomen was non-distended with positive bowel sounds. Tenderness was noted in the right upper quadrant with positive Murphy’s sign.
Laboratory investigations were normal except elevated liver function tests (LFTs) that showed aspartate aminotransferase 93 IU/L, alanine aminotransferase 74 IU/L, total bilirubin 7.0 mg/dL, direct bilirubin 4.1 mg/dL, indirect bilirubin 2.9 mg/dL and alkaline phosphatase 1050 IU/L. Carbohydrate antigen 19-9 (CA19-9) level was in the normal range.
Abdominal ultrasound showed an irregularly thickened GB with mild dilation of the extrahepatic bile duct (figure 1). CT (figure 2) and MR cholangiopancreatography of the abdomen revealed a markedly thickened contracted GB with submucosal hypoattenuated nodules. Endoscopic retrograde cholangiopancreatography (ERCP) revealed opacification of the biliary tree and cystic duct with no common bile duct (CBD) dilation, mucosal irregularity, filling defect or stricture. The attached radiological images show non-specific features that are not pathognomonic to XGC or GB cancer.
Laparoscopic cholecystectomy was converted to an open cholecystectomy with liver resection due to extensive adhesions.
Surgical pathology revealed subacute cholecystitis with xanthogranulomatous inflammation without evidence of malignancy as shown in figure 3. Following surgery, the patient’s symptoms and LFTs improved dramatically and she was discharged to follow-up with her primary care physician.
Our elderly patient presented with obstructive jaundice and radiological investigations revealed a thickened GB which raised the possibility of GB cancer. Only about 20% of patients with XGC present with obstructive jaundice as seen in this case which supports the fact that it is not a frequent form of presentation. When it occurs, it is usually due to cholestasis from spread of XGC causing CBD stenosis or strictures or due to Mirizzi syndrome that has been associated in up to 12.8% of cases though not seen in this case.6 10 11 About 96% of patients may present with abdominal pain likely due to acute cholecystitis6 with positive Murphy's sign as noted in our case. Several studies have shown the strong association between gallstones and XGC.3 4 11 Over time, gall stones may lead to stasis and rupture of Rokitansky-Aschoff sinuses or mucosal ulceration leading to extravasation of bile into the GB wall which incites a host of inflammatory cascade with phagocytosis of biliary lipids by macrophages and fibroblasts leading to the formation of xanthoma cells.9 12 Other clinical features may be nausea, vomiting, anorexia, weight loss or abdominal mass.
Studies from the UK, USA, Japan and India have shown possible coexistence of XGC with GB cancer with estimates ranging from 0.2% to 12.5%3 9 13 14 A recent study showed that XGC may be associated with a precancerous lesion of GB cancer probably due to its distribution of macrophages as well as upregulation of oncogenes and tumour marker expression.15 Patients with coexisting GB cancer are more likely to present with weight loss, anorexia, jaundice and a palpable mass.16 The main difficulty in studying the precancerous lesions of GB is the fact that it is impossible to perform a follow-up because the diagnosis is established after the cholecystectomy. Therefore, evidence relating these lesions to cancer is determined indirectly.
Macroscopically, the GB is thickened with yellow nodules formed of inflammatory foci extending to adjacent structures like the liver, duodenum, transverse colon and omentum.4 Histology usually reveals granulomatous giant cells, lymphocytes, fibroblasts, histiocytes, mucosal ulceration, cholesterol clefts, haemosiderin deposits and lipid-laden macrophages which could be rounded, foamy macrophages or spindle-shaped cells with granular cytoplasm and elongated cells4 (figure 3).
Laboratory tests often show non-specific derangements as shown in our patient with predominant cholestatic pattern. The CA19-9 tumour marker has been shown to be unreliable in differentiating XGC from GB cancer as it can be high in both the conditions.11 Likewise CA19-9 can be elevated in various benign hepatobiliary conditions like bacterial cholangitis, biliary obstruction, acute or chronic pancreatitis and cystic fibrosis and liver cirrhosis. F-fluorodeoxyglucose-positron emission tomography has shown some promising results in differentiating between benign and malignant lesions with sensitivity and specificity ranging from 75% to 78% and 82% to 100%, respectively, for the detection of GB cancer.17–19 However, several cases of false-positive results have undermined its utility mainly because inflammatory cells as seen in XGC also have high rates of glucose metabolism similar to malignant cells and can also be picked up.20–22
Ultrasound and CT scan may show non-specific GB wall thickening, cholelithiasis and GB wall hypoechoic nodules or bands23 but only a CT scan showing intramural hypoattenuated nodules occupying more than 60% of the GB wall thickness has significant specificity for the differentiation of XGC from GB cancer.24 The presence of diffuse GB wall thickening, continuous mucosal line, intramural hypoattenuated nodules, absence of macroscopic hepatic invasion and lack of intrahepatic biliary dilation on CT scan could help differentiate XGC from GB cancer with sensitivity and specificity of 83% and 100%, respectively, when three of these five findings are observed.25
ERCP with brush cytology has a high specificity but a low sensitivity for detecting biliary malignancies and often requires transpapillary cholangioscopy and endoscopic ultrasound-guided fine-needle aspiration to increase diagnostic yield.26 27 Fine- needle aspiratione and cytology has shown to be useful in differentiating XGC from GB cancer with a sensitivity of 90.6% and a specificity of 94.7% in detecting GB cancer.28 Surgery is the preferred treatment option and up to 80% of laparoscopic procedures are converted to open surgery mainly due to extensive adhesions, dense fibrosis and concerns for possible malignancy.8 29 Generally, surgical difficulties are often encountered during laparoscopic cholecystectomy leading to suggestions that XGC may be a risk factor for conversion to open surgery in patients undergoing laparoscopic cholecystectomy.30 Intraoperative frozen section can be helpful if the inflammation is confined to the GB.31 However, frozen sections rarely influence the intraoperative decision to do extensive dissection if the inflammation has spread beyond the GB.16 30 Moreover frozen sections have been shown to have high false-negative results.20 31 32 Postoperative prognosis is usually very good and patients tend to make full recovery. Complications include fistulae from GB to the skin or duodenum and a high rate of postoperative infection.4
In conclusion, XGC is a rare, benign, chronic inflammation of the GB that closely mimics GB cancer in its clinical, biochemical, radiological and intraoperative features and only histopathology can definitively differentiate the two conditions.
Competing interests: None.
Patient consent: Not obtained.
Provenance and peer review: Not commissioned; externally peer reviewed.