Surg Today Jpn J Surg (1997) 27:757-761 ~ SU~aYTODAV

�9 Springer-Verlag 1997

Mirizzi Syndrome Caused by Xanthogranulomatous Cholecystitis: Report of a case KWANG CHOON LEE 1, OSAMU YAMAZAKI 1, KATSUHIKO HORII 1, HIROYUKI HAMBA 1, IKKO HIGAKI 1, SANAE HIRATA ~, and TAKESI-n INOVE 2

Departments of ~ Surgery and zPathology, Osaka City General Hospital, 2-13-22 Miyakojima-hondori, Miyakojima-ku, Osaka 534, Japan

Abstract: Xanthogranulomatous cholecystitis (XGC) is a rare inflammatory disease of the gallbladder. In severe cases, in- flammation extends to adjacent structures, and XGC is some- times confused with a malignant neoplasm. We recently diagnosed XGC as the preoperative cause of Mirizzi syn- drome in a patient based on the clinical course. The patient was admitted because of obstructive jaundice, with gallblad- der carcinoma as the suspected cause. The gallbladder was swollen with gallstones and the serum level of carbohydrate antigen 19-9 (CA19-9) was 3 070 U/ml at admission. A percu- taneous transhepatic cholangiodrainage (PTCD) was done, and the common hepatic duct as well as the right and left hepatic ducts were found to be obstructed. Later, the CA19-9 level and swelling of the gallbladder decreased and the ob- struction of the bile ducts disappeared. A cholecystectomy was performed and the intraoperative pathohistological diag- nosis of chronic cholecystitis was made from frozen sections. The pathohistological diagnosis of XGC was made from paraffin-embedded sections. Mirizzi syndrome such as that seen in our patient is a rare complication of XGC. XGC occasionally causes extensive inflammation; thus, performing a conventional cholecystectomy can be unsafe. However, in our opinion, a total, not subtotal, cholecystectomy should be done whenever possible because the incidence of gallbladder carcinoma accompanied with XGC is higher than that with ordinary cholecystitis or gallstones.

Key Words: xanthogranulomatous cholecystitis, Mirizzi syn- drome, carbohydrate antigen 19-9 (CA19-9)

Introduct ion

Xanthogranulomatous cholecystitis (XGC) is an un- common inflammatory disease of the gallbladder char-

Reprint requests to: K.C. Lee (Received for publication on Apr. 3, 1996; accepted on Sept. 3, 1996)

acterized by focal or diffuse destructive inflammation, with various proportions of fibrous tissue, acute and chronic inflammatory cells, and lipid-laden macroph- ages? Xanthogranulomatous tissue often extends into adjacent organs, making it difficult to distinguish XGC from a neoplasm. Recently, we treated a patient with XGC extending to the common hepatic duct and the right and left hepatic ducts, resulting in Mirizzi syn- drome. We herein present the details of the clinical and pathologic features of this case.

Case R e p o r t

A 50-year-old man was admitted to our hospital on August 26, 1994, with a 10-day history of jaundice and dark urine with two episodes of severe backache and right hypochondralgia without fever. His weight had decreased by 2kg within the preceding 20 days. On admission, the patient was afebrile and strongly icteric with tenderness on deep palpation to the right upper quadrant. There was no mass, rebound, guarding, or organomegaly. Laboratory studies showed a white blood cell count of 10100/mm 3, a C-reactive protein level of 4.9mg/dl, a total bilirubin level of 21.0mg/dl, a conjugated bilirubin level of 13.9mg/dl, alkaline phos- phatase activity of 1102IU/1, and a carbohydrate anti- gen 19-9 (CA19-9) level of 3070U/ml.

Ultrasonography showed a mass in the gallbladder measuring about 8cm in diameter, with several gall- stones, an unclear border between the gallbladder and the liver, and dilatation of the intrahepatic bile ducts. Computed tomography (CT) showed a greatly swollen gallbladder and dilatation of the intrahepatic bile ducts (Fig. 1). The diagnosis of obstructive jaundice was made and at first, gallbladder carcinoma was suspected. While performing the percutaneous transhepatic cholangiodrainage (PTCD) procedure, a drainage cath- eter was placed from the left intrahepatic bile duct to

758 K.C. Lee et al.: Xanthogranulomatous Cholecystitis and Mirizzi Syndrome

Fig. 1. Computed tomography (CT) scan on admission show- ing a swollen gallbladder with a low-density area and an un- clear border between the gallbladder and the liver, The intrahepatic bile ducts are dilated

Fig. 3. Cholangiogram 6 weeks after PTCD showing stenosis of the right and left hepatic ducts and the common hepatic ducl, and filling defects in the gallbladder

Fig. 2. Cholangiogram during percutaneous transhepatic cholangiodrainage (PTCD) showing dilatation of the intra- hepatic bile ducts of the left lobe of the liver and an almost complete V-shaped obstruction of the left hepatic duct. The cystic duct is obstructed while the common bile duct looks normal

the common bile duct. The common hepatic duct and the left and right hepatic ducts were thus found to be almost completely obstructed (Fig. 2).

The serum levels of total bilirubin and CA19-9 gradu- ally decreased, with CA19-9 reaching 90U/ml 6 weeks after PTCD began. Repea ted cholangiography after PTCD was thus started and showed that the obstruction of the bile ducts disappeared gradually; however, no abnormal connection between the pancreatic and com- mon bile duct was found (Fig. 3). Ul t rasonography and a CT scan done about 20 days after the PTCD was begun, showed that the swelling of the gallbladder had decreased. Hepat ic arteriography showed irregularity and stenosis of both the right hepatic and the cystic arteries, a pseudoaneurysm of the cystic artery in the arterial phase, and staining of the gallbladder in the venous phase (Fig. 4). Malignant cells were not found in the bile sampled several times through the PTCD cath- eter. A biopsy of the left hepatic and common hepatic ducts was done under percutaneous transhepatic cholangioscopy, but no malignancy was found. An up-

K.C. Lee et al.: Xanthogranulomatous Cholecystitis and Mirizzi Syndrome 759

Fig. 5. A photomicrograph of the gallbladder shows abundant foamy histiocytes (xanthoma cells), a granulomatous reaction with multinucleated giant cells (arrows), and fibrosis, but no atypia of the epithelium. All parts of the gallbladder were affected by xanthogranulomatous cholecystitis

Fig. 4. Hepatic arteriograms showing irregularity and stenosis of the right hepatic and cystic arteries (arrowheads), a pseudoaneurysm of the cystic artery (arrow) in the arterial phase (top), and staining of the gallbladder in the venous phase (arrowheads; bottom)

per gastrointestinal series showed a hemispherical de- fect of the bulbus of the duodenum next to the gallblad- der, but fiber gastroscopy showed the duodenal mucosa to be normal. A barium enema also showed the entire colon to be normal. A preoperative diagnosis of Mirizzi syndrome was thus made.

On October 12, 1994, a laparotomy was done. During the operation, the gallbladder was found to be chroni- cally inflamed with pericholecystic microabscesses. The neck of the gallbladder was found to adhere to the right hepatic and common hepatic ducts. A normograde

cholecystectomy was done and an intraoperative patho- logical examination of frozen sections of the gallbladder showed chronic cholecystitis without malignancy. Dur- ing cholecystectomy, the right hepatic duct was injured, but thereafter was repaired with interrupted sutures. The PTCD catheter was left in place. A pathological diagnosis of XGC was made based on paraffin- embedded sections taken from various parts of the gall- bladder (Fig. 5). The common bile duct was left intact, so a histological inspection was not possible. The gall- bladder stones were more than 95% cholesterol. Thir- teen days after the operation, cholangiography through the PTCD catheter showed bile leakage from the right hepatic duct, so bile drainage was continued. Cholan- giography on day 27 after the operation showed no leakage, and the catheter was clamped for 3 days before being removed on day 30 after surgery. On November 13, 1994, the patient was discharged.

760 K.C. Lee et al.: Xanthogranulomatous Cholecystitis and Mirizzi Syndrome

Discussion

X G C is found in a small proport ion of cholecystectomy specimens, ranging f rom 0.7% 2 to 1.8%; 1 an intermedi- ate incidence of 1.2% had been repor ted f rom Japan? X G C may begin when both obstruction and acute in- f lammation are present. Bile then enters the s t roma of the gallbladder through ulcerations in the surface of the mucosa, or through ruptured Aschoff-Roki tansky si- nuses. Macrophages gather at the site of inflammation and ingest the bile lipids to form large, round, pale xanthoma cells. Edlund and Olsson 4 and Kitagawa et al. 5 repor ted that the t ime between the onset of symp- toms of acute cholecystitis and granuloma formation is 3 or 4 weeks. One pat ient with X G C has also been re- ported in whom irregular hyper t rophy of the gallblad- der developed within 15 days after the onset of symptoms. 6 In our patient, the period f rom the onset of acute cholecystitis to format ion of the granuloma seemed to be about 10 days.

X G C can be unexpectedly found during elective cholecystectomy and is often mistaken for gallbladder carcinoma. The preoperat ive diagnosis of X G C is dif- ficult, and an intraoperative diagnosis f rom frozen sections is often needed to distinguish it f rom carci- noma. ~,7,s Irregulari ty and stenosis of the cystic artery strongly suggest carcinoma. In patients with acute or chronic cholecystitis (or both), the hepatic ducts are seldom both involved. In our patient, gallbladder carci- noma was suspected at first, because both hepatic ducts were obstructed and the serum level of CA19-9 was very high. However , f rom the clinical course, the preoperat ive diagnosis of acute and chronic cholecy- stiffs was made because the gallbladder had decreased in size, the serum level of CA19-9 had decreased, the obstruction of the bile ducts had disappeared, and nei- ther the cytological examinat ion of bile obtained through the PTCD catheter nor pathological examina- tion of the biopsy specimens of the left hepatic and common hepatic ducts had shown malignancy.

CA19-9 is a tumor marker for pancreatobil iary neo- plasms, 9 but slightly increased amounts of CA19-9 can also be associated with benign biliary diseases? ~ Kitagawa et al. 5 repor ted that 6 of 44 patients with X G C had abnormally high serum levels of CA19-9. A de- crease in an originally high serum CA19-9 level indi- cates a benign disease rather than a malignancy. ~2

Mirizzi syndrome is a rare disorder consisting of an obstruction of the common hepatic duct resulting f rom gallstone impaction in either the cystic duct or neck of the gallbladder. ~3 Patients like ours with Mirizzi syn- drome involving obstruction of both hepatic ducts are even more rare? 4,~5 X G C occasionally causes extensive inflammation and transmural fibrosis involving the en- tire gallbladder, extending into the liver and obscuring

structures in the por ta hepatis. 1,16 We therefore think that X G C sometimes causes Mirizzi syndrome. How- ever, Mirizzi syndrome such as that seen in our pat ient is a rare complication of XGC, and to our knowledge only three patients with X G C and Mirizzi syndrome have previously been r e p o r t e d Y 7,~8 One reason may be that X G C is unfamiliar to many general surgeons and histopathologists. 8 Howard et al. 16 has suggested that when severe fibrosis extends into surrounding struc- tures, particularly the liver bed and por ta hepatis, and when a conventional cholecystectomy is unsafe, a subto- tal cholecystectomy is needed if the surrounding struc- tures are not to be injured. However , we think that total, and not subtotal, cholecystectomy should be done if possible, because the incidence of gallbladder carci- noma accompanied with X G C is higher than that with either ordinary cholecystitis or gallstones? ~22 One pa- tient with Mirizzi syndrome was repor ted to have died due to carcinoma developing in the remaining gall- bladder 2 years and 10 months after subtotal cholecystectomy. 23

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