Radiology–Pathology Conference:

Xanthogranulomatous cholecystitis$

Christopher Hsua, Jessica L. Hurwitzb, Alan Schussc, Douglas S. Katza,*aDepartment of Radiology, Winthrop-University Hospital, 259 First Street, Mineola, NY 11501, USA

bDepartment of General Surgery, Winthrop-University Hospital, Mineola, NY, USAcDepartment of Pathology, Winthrop-University Hospital, Mineola, NY, USA

Received 18 September 2002; received in revised form 10 October 2002

Abstract

We report the radiology and pathology of a patient with xanthogranulomatous cholecystitis (XC) and review the literature on this

unusual condition.

D 2003 Elsevier Inc. All rights reserved.

Keywords: Xanthogranulomatous cholecystitis; Gallbladder; Computed tomography; Ultrasound

Xanthogranulomatous cholecystitis (XC) was first de-

scribed as a distinct pathological entity in 1981 by Good-

man and Ishak [1]. XC is an unusual but not rare disease,

with an estimated incidence of between 1% and 2% of all

cases of cholecystitis [2]. The pathologic features parallel

xanthogranulomatous pyelonephritis, the clinical presenta-

tion is usually one of chronic cholecystitis, and it may be

difficult to differentiate it from gallbladder cancer until the

pathologic specimen is examined [3]. In this Radiology–

Pathology Conference, the clinical presentation and imaging

findings of a patient with XC are reviewed, along with the

differential diagnosis.

1. Case presentation

A 59-year-old woman presented to our hospital with

several days of right upper quadrant pain, chills, nausea,

vomiting and tachypnea. She denied melena, dysphagia,

anorexia or weight loss. The patient’s past medical and

surgical history included hypertension, diabetes, coronary

artery bypass graft surgery, a cerebrovascular accident and a

right above-the-knee amputation.

On examination, her vital signs were unremarkable. The

lungs were clear and a grade 2/6 systolic ejectionmurmur was

heard. There was right mid and lower abdominal tenderness

without a palpable mass. Normal bowel sounds were present

and there was no rebound or guarding. The white blood cell

count was 20,000, with 91% neutrophils. Routine admission

labs were otherwise normal. A chest radiograph revealed

cardiomegaly. Broad-spectrum intravenous antibiotics were

begun and the patient was admitted to our institution.

CT of the abdomen and pelvis revealed a markedly thick-

walled and enhancing gallbladder, from which extended a

4.5-cm cystic mass; the mass involved the adjacent distal

stomach and proximal duodenum, narrowing the bowel

lumen. Hypodense nodules were evident in the gallbladder

wall inferiorly (Fig. 1A–C). There was no associated biliary

dilatation or adenopathy. In contrast, 9 months earlier, an

abdominal CT performed for unrelated reasons retrospec-

tively showed sludge and/or tiny stones in an otherwise

unremarkable gallbladder (Fig. 1D).

Sonography also demonstrated the markedly abnormal

gallbladder wall, and the associated complex cystic mass

involving the adjacent bowel. No stones were evident

(Fig. 1E–G), although the study was somewhat limited as

the patient could not hold her breath. Endoscopic sonog-

raphy (not shown) was then performed, which revealed

0899-7071/03/$ – see front matter D 2003 Elsevier Inc. All rights reserved.

doi:10.1016/S0899-7071(02)00589-2

$ From the monthly Radiology–Pathology Conferences at Winthrop-

University Hospital.

* Corresponding author. Tel.: +1-516-663-3800; fax: +1-516-663-3800.

E-mail address: dsk2928@pol.net (D.S. Katz).

Journal of Clinical Imaging 27 (2003) 421–425

gallstones in addition to all the other findings seen on CT

and abdominal sonography. Biopsy of the mass in the antral

region showed chronic inflammatory changes but no evid-

ence of tumor.

Fig. 1. A 59-year-old woman with several days of abdominal pain, vomiting and chills. (A–C) Contrast-enhanced CT images of the abdomen show diffuse

gallbladder wall thickening and enhancement (curved arrows), subtle hypodense intramural nodules (open arrows, B) and a cystic mass extending from the

gallbladder into the wall of the gastroduodenal junction (straight arrows). Inflammatory changes are also present in the adjacent fat. (D) Unenhanced CT

image of the abdomen, obtained nine months earlier for unrelated reasons, reveals sludge or tiny stones in the gallbladder (arrow), which is otherwise

unremarkable. (E–G) Sonographic images of the right upper quadrant show a normal common duct (calipers, E), prominent gallbladder wall thickening

(arrows, E) and the extension of the complex cystic mass from the gallbladder (curved arrows, F–G). (H) Xanthogranulomatous inflammation (hematoxylin

and eosin � 40) is demonstrated in this image of the gallbladder wall, characterized by large foam (xanthoma) cells with clear lipid-containing cytoplasm.

Other inflammatory cells are present including lymphocytes, neutrophils and plasma cells.

C. Hsu et al. / Journal of Clinical Imaging 27 (2003) 421–425422

A cholecystectomy was then performed. Initially, a

laparoscopic approach was utilized, but adhesions necessi-

tated conversion to an open procedure. An inflamed gall-

bladder with an associated nodular, indurated mass

(corresponding to the findings at CT and sonography) were

identified, along with a cholecystoduodenal fistula. The

mass represented an abscess, which was entered and drained

into the pyloroduodenal junction. Two stones were iden-

tified in the abscess. A cuff of gallbladder serosa was left at

the site of cystic duct obstruction, and the fistula was

repaired. An intraoperative cholangiogram showed no evid-

ence of a stricture or stone. Intraoperative cultures revealed

rare gram negative rods and rare Lactobacilli.

The patient was placed on total parenteral nutrition, and

approximately 3 weeks after admission was discharged in

stable condition to a nursing home for rehabilitation.

The gallbladder specimen measured 9.5� 3.5� 3.5 cm.

The external surface was tan brown to red, with patchy areas

of fibrous thickening. The opened gallbladder showed thick,

pasty bile material with embedded black multifaceted cal-

culi measuring up to 1.5 cm. The gallbladder wall varied in

thickness from 2 to 15 mm, and was hemorrhagic and

necrotic with areas of embedded calculi material. Fibrous

thickening was also noted within the gallbladder wall.

Microscopic review of the gallbladder wall (Fig. 1H)

showed acute, focally ulcerating, hemorrhagic and necrot-

izing cholecystitis, superimposed on chronic cholecystitis,

with intramural acute inflammation and numerous foamy

macrophages, consistent with XC.

2. Discussion

Due to the complex nature of the gallbladder and

adjacent abnormalities in our patient, the differential dia-

gnosis included acute cholecystitis, which occasionally may

be complicated by abscess or fistula formation [4], chronic

cholecystitis, XC and carcinoma. All of these disorders are

associated with gallstones and are all more common in

women. Complicating matters significantly, these gallblad-

der diseases cannot be reliably distinguished prospectively

on clinical or radiologic grounds, or even occasionally at

gross inspection at surgery. Additionally, in a minority of

patients, all of these processes may even coexist and are

often not anticipated clinically [4].

The majority of patients with gallbladder carcinoma

present with advanced disease. The diagnosis should be

thought of when the gallbladder wall is greater than 1 cm

in thickness, especially if there is associated asymmetric

mural irregularity, a focal mass or lymphadenopathy.

Gallbladder carcinoma should be the leading differential

diagnosis when these findings are present on cross-sec-

tional imaging studies, as well as some combination of

biliary obstruction at the porta hepatis, extension of the

disease process to the adjacent liver and focal liver

lesions [4]. In a recent report, helical CT of the abdomen

was 85% accurate in the diagnosis of local extent of

gallbladder cancer [5], a significant improvement over

prior studies.

XC, the final diagnosis in our patient, was first described

as a distinct pathological entity in 1981; Goodman and

Ishak [1] reported the first 40 cases from the Armed Forces

Institute of Pathology. XC is an unusual but not rare disease,

with an estimated incidence of between 1% and 2% of all

cases of cholecystitis [2]. The pathologic features parallel

xanthogranulomatous pyelonephritis, and the clinical pre-

sentation is usually one of chronic cholecystitis [3]. There is

an association with obesity and diabetes in some series [6],

and most patients present in the sixth and seventh decades of

life [7]. On examination, less than one-half of patients have

a palpable right upper quadrant mass [7]. There are no

specific clinical or laboratory features. In a review of 12

cases, all patients had right upper quadrant pain, which

varied in duration from 3 days to 8 months. The patients

often had nausea, vomiting and fever [8]. Anorexia and

weight loss may also occur [3].

Fig. 1. (continued )

C. Hsu et al. / Journal of Clinical Imaging 27 (2003) 421–425 423

The exact etiology of XC is uncertain, but the proposed

pathophysiology is as follows: Chronic gallbladder infec-

tion, associated with gallstones in the vast majority of cases,

leads to the development of microabscesses in the wall, with

extension to the Rokitansky-Aschoff sinuses. This sequence

may be due to some combination of obstruction of gall-

bladder outflow, extravasation of bile into the gallbladder

wall and mucosal ulceration secondary to the gallstones.

Histiocytes accumulate in the gallbladder wall as a reaction

to the extravasated bile (which contains bile lipids and

cholesterol), and over time the microabscesses are replaced

by xanthogranulomatous nodules, which further increase the

thickness of the gallbladder wall. Rupture of the serosa may

occur, with extension of the disease process to the adjacent

liver and bowel. A significant localized fibrous reaction may

also occur [2,3,7–9].

On gross examination of the gallbladder in XC, stones

are identified in most cases, along with irregular wall

thickening and poorly demarcated yellow or brown nodules

of varying sizes associated with mucosal ulceration. Culture

of fluid obtained from the gallbladder lumen may yield

growth of E. coli, Klebsiella and Enterococcus. Gangrenous

changes may be present in some cases [3,6,8]. Microscopic

examination of the gallbladder wall reveals the intramural

xanthogranulomatous nodules, which are composed of

histiocytes, giant cells and other chronic inflammatory cells

including lymphocytes and plasma cells, surrounding a

vascular fibroblastic reaction [3]. The nodules usually run

the full extent of the gallbladder wall, with variable exten-

sion to the adjacent fat [10]. Hemosiderin and extravasated

bile along with cholesterol clefts are also present in the

gallbladder wall, and there is usually evidence of intense

but less specific chronic cholecystitis in the rest of the

gallbladder [7].

The first reports of the CT findings of patients with XC

described enlargement of the gallbladder with an irregular,

often markedly thickened and enhancing wall, and loss of

the normal planes between the gallbladder, liver and duo-

denum. Moderate to marked gallbladder wall thickening

was usually apparent on sonography, and an infiltrating

mass was evident on both sonography and CT in some

cases [3,6,7].

As early as 1984, the difficulty in prospectively distin-

guishing between XC and gallbladder carcinoma on cross-

sectional imaging studies was recognized [3]. In a ret-

rospective review of the CT findings in 11 cases of XC

and 17 cases of gallbladder carcinoma by Chun et al. [11],

even when adenopathy, hepatic involvement or biliary

obstruction were present, XC was still the final diagnosis

in some cases. Diffuse gallbladder wall thickening was

more commonly seen with XC, but there was too much

overlap with carcinoma for this to be useful. However,

carcinoma was more probable if there was marked regional

adenopathy, heterogeneous adenopathy or if there were

multiple masses or a large heterogeneous mass extending

to the liver [11].

More recent reports have focused on the identification of

intramural nodules on both sonography and CT, which are

usually due to the xanthogranulomatous nodules and less

likely due to intramural microabscesses. In the review by

Chun et al. [11], intramural low-density nodules were

present in all 11 cases of XC, compared with 7 of the 17

cases of carcinoma. When the nodules occupied a large area

of the gallbladder wall, the diagnosis of XC was much more

likely. On sonography, corresponding hypoechoic nodules

were also identified. Chun et al. [11] also pointed out that

intramural nodules may also be simulated by intramural

abscesses in complicated acute cholecystitis, and even by

the hyperplastic cholecystoses. In 1999, Kim et al. [10]

performed radiologic–pathologic correlation on 19 patients

with XC. Histologically, all had intramural nodules, which

were either microabscesses (n = 11), xanthogranulomas

(n = 5) or a combination (n = 3). CT and/or sonography

showed nodules in 10 patients, and xanthogranulomas were

more detectable on sonography or CT than were micro-

abscesses. The microabscesses were believed to be present

in the earlier phase of the disease, whereas xanthogranulo-

mas were present in the later phase [11]. Parra et al. [12]

reviewed the sonographic and CT findings in 26 patients

with XC. Hypoechoic nodules or bands were identified in

the gallbladder wall on sonography, and a corresponding

hypoechoic band was seen on CT [12].

At surgery, an attempt should be made to differentiate XC

from carcinoma, although this may be difficult; complete

resection should be attempted, even if this entails a partial

(and nonanatomic) hepatic resection [7]. The adhesions,

which are commonly present, often increase the complica-

tion rate and the operating room time [6]. The role of needle

biopsy in suggesting a preoperative diagnosis of XC is

controversial; the diagnosis may not be reliably established

with fine needle aspiration or core biopsy and, if carcinoma

is present, there is concern that the needle tract may be

seeded with tumor [6,7]. Further complicating matters, there

is up to a 10% incidence of carcinoma in XC [7]. Of the 40

original cases of XC from the Armed Forces Institute of

Pathology, there were 8 which had concurrent adenocarci-

noma, including 5 of the gallbladder proper and 3 of the bile

ducts [1]. Of 168 more recent cases of XC from the Armed

Forces Institute, 19 were associated with malignancy, includ-

ing 9 with gallbladder or cystic duct carcinoma [2].

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