Management of Extensive Xanthogranulomatous Cholecystitis Lesions: A Case Report

Introduction

Xanthogranulomatous cholecystitis (XGC), first described as a benign gallbladder pseudotumor in 1970, is a rare form of chronic cholecystitis characterized by proliferative fibrosis and infiltration of foam cells and macrophages [1]. Its prevalence varies from 1.3% to 8.8% across regions and study populations, predominantly affecting individuals over age 50 years [1,2]. The clinical manifestations of XGC are non-specific, including abdominal pain, nausea, fever, and jaundice, and often resemble those of acute or chronic cholecystitis [3]. According to previous clinical reports, most such patients have gallstones or bile duct stones. Patients with XGC often present with elevated markers of infection (leukocytes, C-reactive protein, procalcitonin), and up to 30% ~ 50% of XGC patients also have elevated carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) [4]. The increase of tumor markers in XGC increases the difficulty of differentiating XGC from gallbladder cancer. In addition, it resembles gallbladder cancer (GBC) due to its destructive inflammation and frequent extension into adjacent tissues [3,4]. Extensive XGC lesions, defined here as those exceeding 10 cm with extensive involvement of surrounding organs, pose distinct management challenges due to widespread, dense adhesions and hepatic invasion. This report details a rare case of extensive XGC, highlighting its diagnostic challenges, surgical management, and long-term outcomes, to contribute to the limited body of documented cases.

Case Report

A 72-year-old woman presented with a 20-year history of intermittent recurrent abdominal pain and fever, which had worsened over the past 3 months. These symptoms were accompanied by a marked reduction in appetite and an unintentional weight loss of approximately 10 kg. She reported no jaundice, although fever was noted in her long-term history. Physical examination revealed a palpable mass in the right upper quadrant below the costal margin, measuring approximately 16×10cm. The mass was firm, well-defined, fixed, and mildly tender. Murphy’s sign was negative. Preoperative laboratory tests, including infection markers, procalcitonin (PCT), and liver function, were within normal limits. Her CA19-9 was mildly elevated at 130 U/mL (reference range: <43 U/mL) on admission.

Initial ultrasound imaging suggested gallstones with possible inflammatory or neoplastic lesions. CT imaging revealed a significantly distended gallbladder that had lost its normal morphology, with multiple internal septations and low-density fluid-filled areas. Small, calcified gallstones were scattered within the gallbladder body, and the boundaries between the gallbladder, inferior liver edge, right anterior abdominal wall, and adjacent intestines were indistinct, showing a prominent edematous zone (Figure 1A, 1B). MRI confirmed diffuse gallbladder wall thickening with multiple cystic lesions, septate stones, and pericholecystic exudative effusion. The lesion extended to the inferior liver edge and right anterior abdominal wall, with adhesions to adjacent intestines. The cystic duct was intermittently visible, showing filling defects consistent with stones. T2-weighted axial MRI depicted an inflamed, enlarged gallbladder with surrounding exudation, measuring approximately 107×76×96 mm. MRCP revealed dilatation of the hilar bile ducts and left intra-hepatic bile ducts (Figure 2A–2C).

The patient was diagnosed with xanthogranulomatous cholecystitis (XGC), and surgical resection was recommended following a multidisciplinary team (MDT) discussion. Initially, a laparoscopic cholecystectomy was attempted. However, intraoperative findings revealed a mass in the right upper abdomen with significant adhesions to the abdominal wall and surrounding organs, necessitating conversion to open surgery. The adhesions between the hollow organs were carefully dissected, enabling gradual mobilization of the gallbladder. Due to dense adhesions in the gallbladder bed, a hepatic wedge resection at the gallbladder bed was performed. The right hepatic duct and common bile duct wall were densely adherent to the mass, requiring careful separation. Due to dilatation of the hilar bile ducts and left intra-hepatic bile ducts and uneven-sized stones in the gallbladder, a common bile duct exploration with choledochotomy was performed to determine whether there were residual stones or lesions in the common bile duct. After that, T-tube drainage was placed due to the severe cholangitis and the possibility of postoperative common bile duct stenosis. Intraoperative cholangiography confirmed no residual stones in the common bile duct, and no stenosis or injury to the intra-hepatic or extrahepatic bile ducts, with smooth contrast flow into the duodenum and no extravasation (Figure 3).

The resected gallbladder specimen (Figure 4A) contained numerous black stones, approximately 5 mm in diameter, and yellowish, turbid, pus-like fluid. A solid mass at the gallbladder base, measuring approximately 5×3 cm, consisted of abundant yellow granulation tissue. Histopathological examination with hematoxylin-eosin (HE) staining (Figure 4B) confirmed the diagnosis of xanthogranulomatous cholecystitis (XGC) with abscess formation, characterized by significant fibrous tissue hyperplasia, hyaline degeneration, and dense infiltration of histiocytes, foam cells, neutrophils, and chronic inflammatory cells.

The patient recovered uneventfully following surgery and was discharged on the 7th postoperative day. Her CA19-9 level normalized before discharge. No abnormalities were reported during a 7-year follow-up period.

Discussion

Xanthogranulomatous cholecystitis (XGC), also known as fibrous granulomatous cholecystitis or bile granulomatous cholecystitis, is a rare form of cholecystitis, accounting for approximately 0.7% to 13.2% of all cholecystitis cases [1,2,4]. Although its exact pathogenesis remains unclear, XGC is thought to result from a combination of acute inflammation and obstruction. Elevated intraluminal pressure within the gallbladder facilitates bile infiltration into the gallbladder wall through mucosal ulcers or ruptured Rokitansky-Aschoff sinuses (RAS), triggering an inflammatory response in adjacent tissues [3]. The bile is then degraded into insoluble cholesterol and bile lipids, which are phagocytosed by macrophages to form foam cells, leading to the development of yellow granulomas characterized by extensive fibroblast proliferation [3]. This inflammatory process often extends to surrounding tissues and organs, causing dense adhesions that complicate cholecystectomy.

Clinically, XGC presents with non-specific symptoms such as abdominal pain, nausea, fever, and jaundice, which can mimic acute cholecystitis during acute episodes [2,5]. Notably, 80% to 90% of XGC patients have comorbid gallstones or bile duct stones, with most seeking medical attention due to concurrent acute or chronic cholecystitis [2,6]. Elevated tumor markers, including carcinoembryonic antigen (CEA) [7], carbohydrate antigen 19-9 (CA19-9) [8,9], and carbohydrate antigen 125 (CA125) [10], have been reported in a minority of patients. In this case, the patient’s CA19-9 was mildly elevated at 130 U/mL (reference range: <43 U/mL) on admission but normalized after surgery. This elevation complicates the differentiation of XGC from gallbladder carcinoma (GBC), as inflammatory stimulation in XGC can increase glycoprotein secretion by bile duct epithelial cells. Moreover, approximately 25% of GBC patients are CA19-9-negative, underscoring the limitations of serological tests alone for accurate differential diagnosis [11]. In addition, with the development of AI (artificial intelligence), deep-learning (DL) models combining clinical characteristics and CT images demonstrated its ability to effectively differentiate XGC from GBC preoperatively, which significantly aid surgeons in making surgical decisions [12].

In complex cases where distinguishing XGC from GBC is challenging, ultrasound-guided fine-needle aspiration cytology (FNAC) is a valuable diagnostic tool, achieving a diagnostic accuracy of up to 97% when routine imaging fails [13]. Image-guided percutaneous fine-needle aspiration biopsy (FNAB) can also aid in diagnosis but is limited by technical difficulties in sampling deep lesions, small tissue yields, and variable sensitivity and specificity depending on sample quality. Additionally, preoperative biopsy of potentially malignant GBC carries a risk of implantation metastasis[14]. Therefore, in cases where GBC is strongly suspected, intraoperative frozen section (FS) examination is preferred over FNAB [6].

Surgical intervention remains the primary treatment for XGC, with laparoscopic cholecystectomy as the preferred approach [1,2,15,16]. However, the conversion rate to open surgery ranges from 10% to 80%, significantly higher than that of routine laparoscopic cholecystectomy [11]. The extensive inflammatory process in XGC often leads to dense adhesions, fistula, and complications in approximately 30% of patients, such as gallbladder perforation, bile duct obstruction, liver abscesses and fistulas to the liver, duodenum, or stomach, making laparoscopic surgery particularly challenging. It has been reported that surgical complications are also more frequent, with an incidence of 20.7~46.1% compared to 2.6% in standard laparoscopic cholecystectomy [15]. A systematic review [11] that analyzed all the clinical research data of XGC published in the database up to June 2020 showed that 6% (56/964) of the patients presented wound infections after surgery. Among the 439 patients, 11 presented with biliary fistula, while 17/655 (3%) patients had bile leakage or biliperitoneum. In addition, 9/491 (2%) of the patients had bile tract lesions, and 5/294 (2%) of the patients had residual choledocholithiasis. The possible causes of these complications, apart from extensive fibrotic and inflammatory nature of the disease, may also be related to surgical factors, including intraoperative conversion to laparotomy, and additional complex surgical procedures such as wedge hepatectomy or cholangiectomy.

In summary, XGC is a diagnostically challenging condition requiring a multidisciplinary approach for accurate diagnosis and effective management. Surgical intervention, although definitive, is often complicated by the disease’s tendency to involve surrounding organs and tissues, as well as its potential for malignant transformation. For patients suspected to have malignant tumors before surgery, laparoscopic surgery is not recommended. Instead, intraoperative frozen section analysis should be conducted to effectively avoid tumor implantation and metastasis and secondary surgery. To the best of our knowledge, this case is one of the few reported instances of extensive XGC lesions in the literature, providing valuable insights into the optimal management of this rare condition. These findings highlight the importance of preoperative imaging, intraoperative pathological evaluation, and tailored surgical strategies to optimize patient outcomes.

Conclusions

Xanthomatous granuloma is a rare benign cholecystitis charactered by xanthomous granuloma of gallbladder wall, which is often difficult to distinguish from GBC. Since preoperative biopsy can increase the risk of tumor implantation and metastasis as well as the incidence of complications, intraoperative frozen section was carried out to reduces the misdiagnosis of XGC or gallbladder cancer and facilitate selecting the optimal surgical strategy. Laparoscopic cholecystectomy is the preferred treatment for benign gallbladder diseases. However, cholecystectomy is recommended for XGC with unclear anatomical structure and severe adhesions around the gallbladder, due to the relatively higher complication rate and conversion rate of laparoscopic surgery.