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Xanthogranulomatous cholecystitis is an uncommon variant of chronic cholecystitis characterized by the presence of greyish yellow nodules or streaks in the gallbladder wall, mainly caused by lipid-laden macrophages [1]. Although well defined pathologically, xanthogranulomatous cholecystitis still remains difficult for the radiologist to recognize because some of the sonographic [2,3,4] and CT [5, 6] features of the disease are nonspecific, such as gallbladder wall thickening and calculi. This article describes the clinical, sonographic, and CT findings in 26 patients with histologically diagnosed xanthogranulomatous cholecystitis. In five of these patients, the pathologic findings were compared with the results of a sonographic study of the surgical specimen.

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The clinical records and radiologic findings of 26 patients with histologically confirmed xanthogranulomatous cholecystitis were studied retrospectively. The study included 15 women and 11 men having a mean age of 63 years (range, 32-86 years). Also noted from the records was a history of biliary colic, cholecystitis, or pancreatitis. Patients underwent sonography after fasting for at least 6 hr. The following factors were analyzed: presence of gallstones (number and size); presence of biliary sludge; thickness of the gallbladder wall, its echogenicity, and the presence of intramural nodes or bands; loss of interface between the gallbladder and the liver; pericholecystic fluid; ductal dilatation; and choledocholithiasis. Thickening of the gallbladder wall was considered abnormal if it exceeded 3 mm and was defined as diffuse (>50% involved) or focal (<50%) according to Kim et al. [4]. Sonography was performed with a Tosbee (SSA-240A; Toshiba Medical Systems, Tokyo, Japan) or a 128XP/10 (Acuson, Mountain View, CA) unit with a 3.5-MHz vector or a 4-2.5-MHz convex transducer. The average time between the sonographic study and cholecystectomy was 70 days.

Nine patients underwent CT. CT was performed with a Somatom AR.T scanner (Siemens, Erlangen, Germany) with 1-cm sections at 10-mm intervals through the abdomen before and after IV administration of a nonionic contrast agent in six patients and without IV contrast medium in three patients; all patients received oral contrast material. CT findings analyzed were the presence of gallstones; thickness of the gallbladder wall (>3 mm), its density, and the presence of mural nodes or bands; loss of interface between the gallbladder and the liver; pericholecystic fluid; ductal dilatation; and choledocholithiasis. Uptake of the contrast medium by the gallbladder mucosa was also studied. The average time between CT and cholecystectomy was 42 days.

In five patients, a sonographic study of the surgical specimen was also made. The gallbladder was fixed with 10% buffered formalin. Histologic sections were cut at 3 μm and were stained with H and E. Sonography was performed with a 7.5-MHz linear transducer (L7; Acuson) with a 2.5-cm standoff cushion.

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The clinical findings are summarized in Table 1. Fourteen patients had a history of cholecystitis, six had biliary colic, three had gallstone pancreatitis, two had tumors of the gallbladder or biliary tree, and the other had gallstone ileus. The most frequent symptoms during the acute phase of cholecystitis were right hypochondriac and epigastric pain and vomiting. All patients also had a positive Murphy's sign and leukocytosis. The blood cultures performed in two patients and intraoperative bile cultures in another two were sterile.

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TABLE 1 Clinical Findings in 26 Patients with Xanthogranulomatous Cholecystitis

The sonographic findings are presented in Table 2. All patients had cholelithiasis, with most having fewer than five gallstones. Nine patients had biliary sludge and two thirds had a gallbladder wall thicker than 3 mm. This thickening of the wall was diffuse in 16 patients and focal in two. In five patients, a hypoechoic band was observed around the gallbladder (Fig. 1), and in four patients hypoechoic nodules were seen (Fig. 2). In all patients, the gallbladder wall was hyperechoic in comparison with the liver. The wall was well defined in all but four patients. The two patients with biliary adeno-carcinoma had intrahepatic bile duct dilatation. Three patients had extrahepatic bile duct dilatation and two patients had choledocholithiasis. Five of the cholecystitis patients presented with preoperative complications: one with an enterobiliary fistula and the other four with a pericholecystic abscess. Six of the patients with cholecystitis had sonography both after presentation and at follow-up (range, 42-149 days; mean, 80 days). In one patient, the gallbladder wall thickening returned to normal. In all six patients, however, the hypoechoic band or nodules in the gallbladder wall were not seen in the follow-up examination.

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TABLE 2 Sonographic Findings in 26 Patients with Xanthogranulomatous Cholecystitis

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Fig. 1. —60-year-old man with xanthogranulomatous cholecystitis. Sonogram shows thick hypoechoic band (cursors).

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Fig. 2. —73-year-old woman with xanthogranulomatous cholecystitis. Sonogram shows thickened gallbladder wall (cursors) with hypoechoic nodule (arrow), neck stone, and small pericholecystic fluid collection (c).

Eleven CT scans were obtained in nine patients. Table 3 summarizes the results. The gallbladder was thickened in six patients, diffusely in four and focally in two. Cholelithiasis was identified in three patients, and one patient had “porcelain” gallbladder. One patient had a pericholecystic abscess. The gallbladder wall was well defined on CT in all but two patients. Three gallbladders showed hypodense bands, a finding that was similar to sonographic findings. In one patient the band measured 16 H and surrounded the gallbladder. Two of these patients were given IV contrast material and their scans showed homogeneous contrast enhancement of the gallbladder mucosa (Fig. 3A). Follow-up CT performed in one of these patients 13 days later showed an almost complete reduction of the gallbladder hypodense band, but the uniform uptake by the mucosa persisted (Fig. 3B). No patient showed rim enhancement as is observed in xanthogranulomatous pyelonephritis. Comparison of the sonographic and CT findings in the same patients showed similar results except that lithiasis was better detected on sonography.

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TABLE 3 CT Findings in Nine Patients with Xanthogranulomatous Cholecystitis

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Fig. 3A. —59-year-old woman with xanthogranulomatous cholecystitis. Contrast-enhanced CT scan shows thickened gallbladder wall. Note contrast enhancement in mucosa and hypodense outer band.

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Fig. 3B. —59-year-old woman with xanthogranulomatous cholecystitis. CT scan obtained 13 days after A shows smaller hypodense band. Note persistence of enhancement in mucosa.

Sonography of the surgical specimens showed a well-defined hypoechoic area corresponding to the xanthogranulomatous foci (Fig. 4A,4B,4C) in all patients. All patients had a history of cholecystitis. The mean time between the cholecystitis episode and surgery was 163 days (range, 56-241 days). All patients had similar preoperative findings, with a thickened wall or a hypoechoic band or nodules or both. Two underwent CT, with one showing a pericholecystic abscess and the other a hypoattenuated band.

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Fig. 4A. —60-year-old woman with xanthogranulomatous cholecystitis. Photograph of specimen from gallbladder shows xanthogranulomatous changes in wall. Xanthogranulomatous nodules appear as yellowish nodules.

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Fig. 4B. —60-year-old woman with xanthogranulomatous cholecystitis. Photograph shows histologic section of xanthogranulomatous nodule. (H and E, × 1)

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Fig. 4C. —60-year-old woman with xanthogranulomatous cholecystitis. Sonogram shows nodule (cursors) as well-defined hypoechoic mass.

The surgical treatment was open cholecystectomy in 14 patients (three in the setting of more extensive surgical intervention) and laparoscopic cholecystectomy in 12 patients. In the latter group, surgery was complicated by adhesions or a thickened gallbladder wall in 10 cases (83%). In six patients the gallbladder ruptured, with extravasation of lithiasis into the peritoneal cavity. Two patients undergoing laparoscopy required conversion to open surgery, in one case because of a short cystic duct and in the other because of bleeding from the cystic artery. In another two patients, it was necessary to widen the umbilical hole. The average hospital stay for patients undergoing open surgery was 21 days (range, 9-60 days) and for patients having laparoscopic cholecystectomy, 5 days (range, 3-10 days).

Pathologically, in addition to xanthogranulomatous changes, all patients had chronic cholecystitis and 10 had acute cholecystitis superimposed on chronic cholecystitis. In addition, two patients had adenocarcinoma, and five patients had lymphadenopathy, which histologic analysis showed was reactive lymphadenitis in four patients and metastatic disease in one of the cancer patients.

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Xanthogranulomatous cholecystitis is an uncommon form of chronic cholecystitis, representing between 0.7% and 13.2% of gallbladder disease [3, 7] and mainly affecting women between 60 and 70 years old [3, 4, 8]. Its importance lies in the fact that clinically and radiologically it can be confused with the prognostically far more serious condition of carcinoma of the gallbladder [7, 9].

Although the mechanism leading to this condition remains unclear, extravasation of bile into the gallbladder wall, with involvement of Rokitansky-Aschoff sinuses, or extravasation through a small ulceration in the mucosa, appears to be a precipitating factor [4]. The presence of calculi or biliary tree obstruction may play an important role [6], as in xanthogranulomatous pyelonephritis. In our series as in others reported in the literature [1, 3], almost all patients had cholelithiasis or biliary obstruction.

Clinical findings on physical examination and the results of laboratory tests do not appear to be of use in differentiating this gallbladder disorder from other more frequent types [1, 7]. The vomiting, upper right quadrant pain, positive Murphy's sign on sonography, and leukocytosis observed in our patients are similar to the findings described in other types of cholecystitis. A history of repeated episodes of biliary colic or pancreatitis is also fairly common. Of greater interest is the possible association of xanthogranulomatous cholecystitis with other diseases, especially tumors of the gallbladder and bile ducts. Although disagreement exists on this matter [10], both our series and other reported series support the existence of this association [7, 11]. Also, patients presented with a high comorbid factor such as a perforated gallbladder, abscess formation, or enterobiliary fistula [1, 12]. These comorbid factors were seen in 23% of our patients. Two patients presented with enterobiliary fistula and four patients had a perforated gallbladder with abscess formation. In our series, probably because of the small number of cultures performed, no organism was isolated, although several organisms, such as Escherichia coli, Klebsiella species, and Enterococcus species, have been isolated in bile cultures from patients with xanthogranulomatous cholecystitis and in xanthogranulomatous pyelonephritis [3].

Although gallstones and a thickened and echogenic gallbladder wall are frequent radiologic findings, they are nonspecific. The presence of sludge is also common and was observed in 35% of our patients, a figure slightly lower than the 50% reported by Casas et al. [3]. Three groups of researchers have reported hypoechoic nodules and bands in the gallbladder wall to be the most characteristic findings in the disease [2,3,4]. In our series, nodules were observed in four patients (15%), fewer than the eight (73%) of 11 patients reported by Kim et al. [4]. A hypoechoic band was seen in five patients (19%), a percentage similar to that of Casas et al. Because sonography is currently the technique of choice in the investigation of patients with gallbladder disease, we performed sonography in five surgical gallbladder specimens showing nodular xanthogranulomatous changes to determine whether the xanthogranulomatous nodules appear sonographically as hypoechoic areas. In all five cases, we confirmed that xanthogranulomatous nodules did in fact behave as well-defined hypoechoic areas. This finding suggests that the hypoechoic bands might be caused by a more generalized involvement of the mucosa, which is sometimes evident in the surgical specimen [8]. The explanation of this sonographic appearance might lie in the lipid content of the lesion or in its cellular density.

As with sonography, thickening of the gallbladder wall was also the most frequent CT finding. Two patients presented with a hypoattenuated band around the gallbladder similar to that described by Chun et al. [6] and Hanada et al. [13], and homogeneous uptake of contrast material by the gallbladder mucosa. In these patients, CT was performed during an acute episode of cholecystitis. One patient underwent follow-up CT 13 days later, which showed that the band had disappeared, but the mucosal uptake of contrast material persisted together with low-attenuation nodules within a thickened wall. In other cases, thickening of the wall was indistinguishable from that found in other gallbladder diseases, and in three patients the wall thickness was normal. This experience suggests that the most characteristic CT findings may be more apparent in the acute phase of the disease [6]. One noteworthy finding in our series was the presence of xanthogranulomatous changes in a patient with a porcelain gallbladder similar to those described by Düber et al. [9], suggesting that xanthogranulomatous changes can also be found in this type of gallbladder.

In addition to sonography and CT, other methods appear useful or promising in the diagnosis of xanthogranulomatous cholecystitis. Fine-needle aspiration biopsy has been used in several cases with good results [3, 14]. Sonographic contrast agents appear to give a type of vascular enhancement that, although not specific, could be helpful in the diagnosis [15]. To our knowledge, only one published report exists of MR imaging in a patient with xanthogranulomatous cholecystitis; those authors could not differentiate xanthogranulomatous cholecystitis from gallbladder carcinoma [16].

Nearly all the patients who underwent laparoscopic cholecystectomy presented some difficulty during the surgical procedure. However, only two patients required conversion to open surgery. This experience indicates a need for a wider study to determine whether xanthogranulomatous cholecystitis is a risk factor for conversion to open surgery in patients treated with laparoscopic cholecystectomy.

In conclusion, we consider that the presence of hypoechoic nodules or bands in a thickened gallbladder wall, together with calculi in a patient with chronic disease, is highly suggestive of xanthogranulomatous cholecystitis. The preoperative identification of xanthogranulomatous cholecystitis can be important in the proper surgical management of these patients and in the differential diagnosis with other gallbladder diseases.