Xanthogranulomatous cholecystitis vs Gallbladder carcinoma

Xanthogranulomatous
Cholecystitis:
Ultrasound, CT, and MRI findings
Ultrasound
CT
Julia T. Chu, HMS IV
Laura Avery, M.D.
Gillian Lieberman, M.D.
MRI

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Patient:
DDx: RUQ abd
Agenda
53yo M with RUQ abd
pain
pain
Imaging Modalities: available to image our patient
Radiologic Findings:
US, CT, MRI
gangrenous cholecystitis, adenomyomatosis
review of anatomy and pathophysiology
Pathology Dx: Xanthogranulomatous
Management: Depends on radiologic Dx!
Take-Home Points
cholecystitis

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Our Patient:
History & Physical Exam
Hx: 53yo M with intermittent RUQ abd pain for 2
years; no fever/chills, nausea/vomiting, weight
loss, or food association
PMH:
Meds:
SH:
Exam:
Labs:
DM 2, hyperlipidemia, HTN
Metformin, ASA, lisinopril, atorvastatin
Plumber married w/ children;
(+) smoking, (-) EtOH
(+) Murphy sign, (+) guaiac
Leukocytosis, ↑
Alk
Phos, ↑
LFTs, ↑
GGT

Vascular
Infarct
Pyelophlebitis
Mesenteric thrombosis
Adrenal infarct
Occlusion
Embolism
Clinical DDx:
RUQ abd
(by mnemonic)
pain
“V I N D I C A T E”
Neoplasm
Degenerative
Renal vein thrombosis
Inflammation/Infection Carcinoma
Osteoarthritis
Cellulitis, Osteomyelitis Cholangioma
Diaphragmatic abscess Pancreatic carcinoma
Trichinosis, TB, Herpes zoster Hodgkin disease
Hepatitis, Hepatic abscess
Cholecystitis, Cholangitis
Lymphosarcoma
Neuroblastoma
Intoxication/
Idiopathic
Duodenitis, Diverticulitis, Colitis Adrenal carcinoma
Alcoholic hepatitis
Pancreatitis, Pyelonephritis Multiple myeloma
Ulcer
Ulcer, Mesenteric adenitis
Gout
Waterhouse-Friderichsen syndrome
Allergic/
Autoimmune
Rheumatoid
spondylitis
Congenital/
Acquired
Anomaly
Ventral hernia
Incisional
hernia
Diverticulum
Obstruction
Cyst
Hydronephrosis
Endocrine
Hyperparathyroidism
Trauma
Contusion
Cough
Hemorrhage
Laceration
Rupture
Herniated disc
Spine fracture

DDx:
Gallbladder carcinoma
Cholecystitis
and
cholelithiasis
Hepatic flexure
syndrome
Carcinoma of the colon
with obstruction
Pancreatitis
Colitis Thus, would involve which conditions?
Diverticulitis
Pancreatic calculus
Pyelonephritis
Embolic nephritis
Carcinoma
Subphrenic abscess
Hepatitis
Liver abscess
RUQ abd
(by anatomy)
Pneumonia/empyema pleurisy
pain
Budd-Chiari syndrome
Our patient’s main DDx, based on:
RUQ pain
(+) Murphy Sign
leukocytosis,
Renal calculus
Legend: Liver Pancreas
Bile duct Small bowel
Gallbladder Large Bowel
Renal System Others
Laceration
Cholangitis
Common duct stone
Duodenal ulcer
would be most likely centered on which organ?
Carcinoma of the
pancreas
www.wrongdiagnosis.com

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Imaging Modalities:
Available/Applicable to Our Patient
with RUQ pain, ↑
WBC, (+)Murphy
Ultrasound (US): abdomen/gallbladder to look for gallstones, aneurysm
Nuclear Medicine: cholescintigraphy (or HIDA scan) with or w/out
cholecystokinin to evaluate the function of the gallbladder and the bile
ducts
X-ray: Upper GI series to rule out stomach/duodenum conditions;
abdomen; colon barium enema; chest x-ray to rule out pneumonia
Computed Tomography (CT): abdomen to further evaluate the
gallbladder for mass/carcinoma as well as other abd organs such as the
nearby pancreas
Magnetic Resonance Imaging (MRI): T1 with fat saturation, T2 to
assess soft tissue changes such as fluid, inflammation, edema; MR
cholangiopancreatography (MRCP) to visualize the biliary tract and
pancreatic ducts
Invasive: cholangiography, percutaneous cholecystostomy, endoscopic
retrograde cholangiopancreatography (ERCP)
American College of Radiology, www.acr.org

Arrive at Our Dx, Step by Step …
H&P:
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Hx
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Exam –
RUQ abd
pain
(+) Murphy sign
Labs – Leukocytosis
Clinical DDx:
• Cholecystitis
• Cholelithiasis
• Choledocholithiasis
• Cholangitis
• Hepatitis
• Pancreatitis
Imaging: Ultrasound

Normal Liver
Our Patient:
Findings on Ultrasound
Sagittal
Gallbladder
Courtesy of Dr. MaryEllen Sun (BIDMC PACS)
Patient
Hyperechoic fatty liver with
abnormality in the region
contiguous to gallbladder
Abd aorta
√ Marked irregular GB wall thickening
√ Cholelithiasis with (+) US Murphy sign
Film Findings: hyperechoic fatty liver, markedly thickened
gallbladder wall, cholelithiasis with (+) US Murphy sign
Impression: Gangrenous cholecystitis vs GB carcinoma
Sagittal
Partners CAS

Arrive at Our Dx, Step by Step …
H&P:
• Hx – RUQ abd pain
• Labs – Leukocytosis
• Exam – (+) Murphy sign
Clinical DDx:
• Cholecystitis
• Choledocholithiasis
• Cholangitis
• Hepatitis
• Pancreatitis
US Findings:
• Irregular gallbladder wall
thickening
Imaging: CT to evaluate gallbladder wall
thickening vs “mass”; why?
• gallbladder carcinoma has a poor prognosis of
85% mortality within 1 year of diagnosis
• need to further evaluate the US findings with
more imaging studies before embarking on any
treatment
US DDx:
• Gangrenous cholecystitis
• Gallbladder carcinoma

Our Patient: Findings on CT scan
Axial, oral C+
Cystic structure
Irregular wall thickening
involving the gallbladder fundus
Gallbladder
Fundus
Cystic duct
Neck
Body
Common
hepatic
duct
Common
bile duct
www.wiltshiresurgery.com
Heterogeneous low density in the adjacent liver
Film Findings: Irregularly thickened wall at the gallbladder
fundus, low attenuation in liver adjacent to the gallbladder, cyst
at the fundus.
Partners CAS

Our Patient: Pertinent negative
findings on CT scan
Coronal, oral and IV C+
Cystic structure
Irregular wall thickening
involving the gallbladder fundus
No pericholecystic
No intra or extrahepatic
fluid or inflammation
biliary
ductal
No wall thickening in the inferior and
medial aspect of the gallbladder
Partners CAS
dilatation
Impression: CT findings suspicious for malignancy. Infection
much less likely given no pericholecystic fluid or inflammation.

Arrive at Our Dx, Step by Step …
H&P:
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Hx
–
Labs –
Exam –
RUQ abd
pain
Leukocytosis
(+) Murphy sign
Clinical DDx:
• Cholecystitis
• Choledocholithiasis
• Cholangitis
• Hepatitis
• Pancreatitis
US Findings:
• Irregular gallbladder wall
thickening
Imaging: MR to further evaluate soft tissue
changes in the gallbladder and the adjacent
liver to assess inflammatory changes and
confirm or rule out malignancy
CT DDx: gallbladder malignancy
CT Findings:
• Irregular wall thickening at the gallbladder fundus
• Cystic structure at the gallbladder fundus
• No pericholecystic fluid or inflammation
• No biliary ductal dilatation
US DDx:
• Gangrenous cholecystitis
• Gallbladder carcinoma

Our Patient:
Findings on MR imaging
Axial T1-weighted Gradient Echo with Fat Sat;
Post-Gadolinium
Arterial Phase
Partners CAS
Axial T1-weighted Hi-Resolution with Fat Sat;
Post-Gadolinium
Slight enhancement of GB wall mucosa, most
prominently involving the fundal portion
Partners CAS
Film Findings: Wall thickening thickened along the gallbladder fundus measuring wall with up hyper-intensity
of the mucosa to 15mm in mostly maximum involving thickness the fundus

Our Patient:
Findings on MR imaging
Axial T1-weighted Gradient Echo with Fat Sat;
Post-Gadolinium,
Arterial Phase
Partners CAS
Axial T1-weighted Hi-Resolution with Fat Sat;
Post-Gadolinium
No clear communication between the fundus and
this cystic collection could be demonstrated
Partners CAS
Film Findings: Small small cystic cyst area at adjacent the fundus to the fundus with ? communication to
the gallbladder measuring that cannot up to 2.0 be cm, clearly (+) rim identified enhancement on MR

Axial T2-weighted with Fat Saturation
Our Patient:
Findings on MR imaging
Irregular wall thickening
involving the gallbladder fundus
Partners CAS
Coronal T2-weighted Single-Shot Fast Spin Echo
(SSFSE)
Gallbladder sludge and stones
Film Findings: Gallstones and, again, irregularly thickened
gallbladder wall involving the fundus
Partners CAS

Our Patient:
Findings on MR imaging
Coronal 2D Thick-Slab Abdomen
(MR Cholangiopancreatography, or MRCP)
Right hepatic duct
Cystic duct
Gallbladder
Major duodenal papilla
Left hepatic duct
Common hepatic duct
Common bile duct
Pancreatic duct
Hepatopancreatic
R and L
hepatic Common ducts
Cystic
Common
duct
Gallbladder
Co
Main pancreatic duct
Com
Hepatopancreatic ampulla
Com
Major duodenal papilla
ampulla Com
(4)
Common
hepatic Gallbladde duct
r
carcinoma
Common
Common
bile duct
Film Findings: No biliary/pancreatic duct obstruction/dilatation
Duodenum
Duodenum
Com
Partners CAS
Copyright ® The McGraw-Hill Companies, Inc.
Impression: Normal biliary/pancreatic http://academic.kellogg.cc.mi.us/herbrandsonc/bio201 ductal system.
McKinley/Digestive%20System.htm
(2)
(1)
(3)

R and L
hepatic Common ducts
Common Cystic duct
CoGallbladder
The Biliary
Main pancreatic duct
Com
Hepatopancreatic ampulla
Com
Major duodenal papilla
Com
Duodenum
Com
(2)
(4)
(1)
Copyright ® The McGraw-Hill Companies, Inc.
Quick Review:
Common Gallbladder
hepatic carcinoma duct
Common
Common
bile duct
(3)
and Pancreatic Ducts
(1) R and L hepatic ducts merge to
form a common hepatic duct
(2)
(3)
(4)
http://academic.kellogg.cc.mi.us/herbrandsonc/bio201_McKinley/Digestive%20System.htm
Common hepatic and cystic
ducts merge to form a common
bile duct
Pancreatic duct merges with
common bile duct at the
hepatopancreatic ampulla
Bile and pancreatic juices
enter duodenum at the major
duodenal papilla

Our Patient:
Findings on MR imaging
Axial T2-weighted with Fat Saturation
↑ T2 signal abnormality (hyper-intensity) surrounding the
gallbladder and adjacent liver parenchyma
No enlarged lymph nodes.
Patent hepatic vasculature.
No ascites.
Film Findings: ↑ T2 signal surrounding the fundus, patent hepatic
Partners CAS
vasculature, no lymphadenopathy or ascities
Impression: Overall MRI findings suggestive of fatty infiltration,
adenomyomatosis likely complicated by chronic cholecystitis;
gallbladder adenocarcinoma cannot be entirely excluded.

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MRI Dx:
What is
Adenomyomatosis?
Definition: benign, abnormal
though non-premalignant
gallbladder mucosal
hyperplasia, muscular wall
thickening, and formation of
intramural diverticula or sinus
tracts called Rokitansky-
Aschoff sinuses
Radiologic Finding: Pearl
Necklace Sign
Very Very small small cystic cystic structures structures
(Pearl (Pearl Necklace Necklace Sign) Sign)
Multiple
gallbladder stones
uodenum
Haradome, H. et al. Radiology 2003. 227(1): 80-8.

Arrive at Our Dx, Step by Step …
H&P:
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Hx
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Labs –
Exam –
RUQ abd
pain
Leukocytosis
(+) Murphy sign
Clinical DDx:
• Cholecystitis
• Choledocholithiasis
• Cholangitis
• Hepatitis
• Pancreatitis
US DDx:
• Gangrenous cholecystitis
• Gallbladder carcinoma
Pathology/Management: Open
cholecystectomy to make the definitive,
final Dx by histology and determine future
management of our patient
MR DDx:
• Adenomyomatosis
• Gallbladder adenocarcinoma
MR Findings:
• Thickened gallbladder wall
• Fundus cyst with ?communication
• Gallbladder stones
• No biliary obstruction/dilatation
• ↑ T2 signal surrounding the fundus
CT DDx: gallbladder malignancy

Our Companion Patient:
Findings on Gross Pathology
Cross section of the resected
gallbladder
Serosa covered with dense
fibrous adhesions
Gross Pathology Findings:
(1) fibrosis and wall thickening
(2) disruption of gallbladder wall
(3) xanthogranulomatous foci
Disruption of the gallbladder wall
Ulcerated mucosal surface
Diffuse wall thickening
Yellow nodules/plaques, or
xanthogranulomatous
foci, extend into
adjacent liver through the wall
Levy, A. et al. Radiographics. 2002. 22(2): 387-413.

H&E stain
Our Companion Patients:
Thickened, fibrotic wall
Levy, A. et al. Radiographics. 2002. 22(2): 387-413.
Findings on Histology
Lipid-laden mø: 2 morphological types
Fibroblasts,
inflammatory cells
Xanthogranulomatous
cholecystitis
focus (blackarrows
( blackarrows above)
Contains:
(1) bile pigment
(2) chronic inflammatory cells
(3) foamy pigment-laden macrophages (mø)
Spindle-shaped Spindle shaped cells
with more granular
cytoplasm and
elongated nuclei
(1)
(2)
Rounded foamy
macrophages
Varadarajulu S, et al. Up-to-Date
No dysplasia or malignancy!

Arrive at Our Dx, Step by Step …
H&P:
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Hx
–
Labs –
Exam –
RUQ abd
pain
Leukocytosis
(+) Murphy sign
Clinical DDx:
• Cholecystitis
• Choledocholithiasis
• Cholangitis
• Hepatitis
• Pancreatitis
US DDx:
• Gangrenous cholecystitis
• Gallbladder carcinoma
Pathology (Final) Dx:
Xanthogranulomatous
cholecystitis
Gross/Histologic Findings:
• Wall thickening with fibrotic serosa
• Xanthogranulomatous foci
• Bile extravasation through disrupted wall
• Lipid-laden macrophages
• Chronic inflammatory cells
MR DDx:
• Adenomyomatosis
• Gallbladder adenocarcinoma
CT DDx: gallbladder malignancy

Dx:
What is
Xanthogranulomatous
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Cholecystitis?
Definition: unusual form of benign, chronic
cholecystitis with focal or diffuse destructive
inflammatory process
Signs and symptoms: RUQ abd pain, fever,
leukocytosis, vomiting, (+) Murphy sign
Hallmarks:
(1) thickened, fibrotic, disrupted gallbladder wall
(2) foamy histiocytes
(3) bile extravasation

Dx:
What is
Xanthogranulomatous
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Cholecystitis?
Pathophysiology: gallbladder or cystic
duct obstruction ↑ gallbladder
intraluminal pressure rupture of
Rokitansky-Aschoff sinuses or mucosal
ulceration extravasation of bile into the
gallbladder wall
s63.4x1.jpg
s63.jpg
bile
bile
s63.jpg
http://anatomy.iupui.edu/courses/histo_D502/D502f04/Labs.f04/digestive%20III%20lab/Lab13index.htm

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Management:
Xanthogranulomatous
Significance of
Cholecystitis
Significance: may simulate malignancy clinically,
radiologically, and pathologically
Management of XG cholecystitis: open
cholecystectomy with complete resection of the
gallbladder due to dense fibrosis, extensive
inflammation, ?coexistent malignancy
Management of GB carcinoma:
(1) aggressive surgery – partial/segmental hepatic
resection or Whipple procedure
(2) no resection at all with chemo/radiation instead

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Take Home Points:
XG cholecystitis: benign yet focally/diffusely
destructive inflammatory gallbladder disease
with (1) fibrosis and wall thickening, (2) bile
extravasation, (3) lipid-laden mø, (4)
acute/chronic inflammatory cells
XG cholecystitis
vs GB carcinoma:
Patients
with carcinoma are more likely to present with
anorexia, weight loss, palpable mass, and
jaundice
Preoperative Dx
by radiographs:
may
significantly alter therapy and patient prognosis
– be careful!

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What happened to Our Patient?
Our patient underwent an exploratory
laparoscopy that was converted to open
cholecystectomy, which went successfully
without any complications
His gallbladder was diagnosed with
xanthogranulomatous cholecystitis without
any associated malignancy by pathology
and histology
Our patient is alive and well as of today in
June, 2008

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Acknowledgements
Gillian Lieberman, M.D.
Laura Avery, M.D.
James Kang, M.D. (resident)
Karen Lee, M.D. (fellow)
Maryellen Sun, M.D. (fellow)

References
Chun KA, Ha HK, Yu ES, Shinn KS, Kim KW, Lee DH, Kang SW, Auh YH. Xanthogranulomatous
cholecystitis: CT features with emphasis on differentiation from gallbladder carcinoma. Radiology. 1997
Apr; 203(1): 93-7.
Guermazi A. Are there other imaging features to differentiate xanthogranulomatous cholecystitis from
gallbladder carcinoma? Eur Radiol. 2005 Jun; 15(6): 1271-2.
Haradome H, Ichikawa T, Sou H, Yoshikawa T, Nakamura A, Araki T, Hachiya J. The pearl necklace sign:
an imaging sign of adenomyomatosis of the gallbladder at MR cholangiopancreatography. Radiology.
2003 Apr; 227(1): 80-8.
Levy AD, Murakata LA, Rohrmann CA Jr. Gallbladder carcinoma: radiologic-pathologic correlation.
Radiographics. 2001 Mar-Apr; 21(2): 295-314.
Levy AD, Murakata LA, Abbott RM, Rohrmann CA Jr. From the archives of the AFIP. Benign tumors and
tumorlike lesions of the gallbladder and extrahepatic bile ducts: radiologic-pathologic correlation. Armed
Forces Institute of Pathology. Radiographics. 2002 Mar-Apr; 22(2): 387-413. Review.
Shuto R, Kiyosue H, Komatsu E, Matsumoto S, Kawano K, Kondo Y, Yokoyama S, Mori H. CT and MR
imaging findings of xanthogranulomatous cholecystitis: correlation with pathologic findings. Eur Radiol.
2004 Mar; 14(3): 440-6.
Srivastava M, Sharma A, Kapoor VK, Nagana Gowda GA. Stones from cancerous and benign gallbladders
are different: A proton nuclear magnetic resonance spectroscopy study. Hepatol Res. 2008 May 27.
Varadarajulu S, Zakko SF. Xanthogranulomatous cholecystitis. Up-to-date. 2007.
Slides 16 and 17 –
http://academic.kellogg.cc.mi.us/herbrandsonc/bio201_McKinley/Digestive%20System.htm
Slide 25 –
http://anatomy.iupui.edu/courses/histo_D502/D502f04/Labs.f04/digestive%20III%20lab/Lab13index.htm