1 SUBMITTED 11 OCT 22 2 REVISION REQ. 2 JAN 22; REVISIONS RECD. 1 FEB 22 3 ACCEPTED 23 MAR 23 4 ONLINE-FIRST: MAY 2023 5 DOI: https://doi.org/10.18295/squmj.5.2023.022 6 7 Preoperative Diagnosis of Xanthogranulomatous Cholecystitis 8 Asma S. AlHatmi, Atheel Kamoona, *Ishaq S. Al Salmi 9 10 Radiology Department, The Royal Hospital, Muscat, Oman 11 *Corresponding author’s email: ishaqalsalmi85@gmail.com 12 13 Introduction 14 A sixty-one years old man, known case of hypertension presented to the hepatobiliary surgery 15 clinic, Royal Hospital, Muscat, Oman, in December 2020 with a history of right upper quadrant 16 pain associated with nausea, vomiting, loss of appetite and jaundice for the past two months. On 17 examination, tenderness and fullness were present over the right upper quadrant. Laboratory 18 investigations showed deranged liver function test with elevated liver enzymes and bilirubin 19 level. The total count of white blood cells and neutrophils were normal. Cancer Antigen 19-9 20 (CA 19-9) was elevated reaching 2364 U/mL and Carcinoembryonic Antigen (CEA) was 21 negative. Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) of abdomen 22 were performed. CT revealed irregular diffuse mural wall thickening of the gallbladder along 23 with few hypoattenuating mural nodules, multiple hyperdense calculi and pericholecystic fluid 24 collection. Poor fat plane to the adjacent liver parenchyma was seen and common bile duct 25 (CBD) was mildly dilated with multiple calculi noted within it. MRI showed a diffusely 26 thickened gallbladder along with few non enhancing mural nodules within the thickened wall 27 which showed iso- to slightly hypointense signal on both T1 and T2-wieghted images and some 28 of them demonstrated reduced signal in opposed images (OP) denoting microscopic fat 29 depositions of xanthogranuloma In post contrast images, smooth luminal surface enhancement 30 along with focal area of early enhancement of adjacent liver parenchyma were noted. The 31 mailto:asmaalhatmi1989@gmail.com mailto:atheel88@gmail.com javascript:if(intFormHasChanged%20==%200)%7bpopupReviewerInfoEMDetails(16219,%209079,'squmj',%200)%7delse%7bpopupReviewerInfoEMDetails(16219,%209079,'squmj',%201)%7d mailto:ishaqalsalmi85@gmail.com diagnosis of Xanthogranulomatous Cholecystitis (XGC) was raised. Endoscopic Retrograde 32 Cholangiopancreatography (ERCP) was performed for biliary decompression and CBD stone 33 extraction and stent insertion. Later, total radical cholecystectomy with resection of segment 34 4B/5 of liver and portahepatis and celiac lymph node dissection were done and showed a 35 gallbladder mass with surrounding greater omental adhesions extending to adjacent liver 36 parenchyma and hepatic flexure with no evidence of liver or peritoneal metastasis. The 37 postoperative period was uneventful. The histopathology report revealed XGC with no evidence 38 of malignancy. XGC is uncommon inflammatory condition of the gallbladder in which the 39 diagnosis can be challenging on both imaging and histopathology due to overlapping features 40 with other serious conditions like carcinoma of the gallbladder. We report the CT and MRI 41 findings of XGC with a literature review. 42 43 Informed patient consent of publication was obtained. 44 45 Comment 46 XGC is a rare type of chronic cholecystitis that was first reported by Christensen et al in 1970.1 47 The underlying pathophysiology is still unclear, although many hypotheses attributed this 48 condition to a bile leak into the gallbladder wall which occurs secondary to Rokitansky sinuses 49 rupture or mucosal injury in long standing high intraluminal pressure of the gallbladder due to 50 obstructing stones. Subsequently, this leads to an inflammatory reaction that will attract more 51 foamy cells and macrophages resulting in chronic infiltrative granulomatous inflammation and 52 fibrosis which may extend to involve the adjacent structures.1,2 The histopathology reveals an ill-53 defined infiltrative yellow mass of thickened gallbladder wall.2 Half of the XGC cases are 54 associated with pericholecystic fat infiltration and hepatic extension. 36% of the cases are 55 associated with biliary obstruction and reactive lymphadenopathy.2,3,4 Microscopically, XGC 56 shows a mixture of xanthogranuloma with foamy histiocytes, macrophages and fibroblasts.2 57 XGC is an uncommon disease with estimated prevalence rate of 0.7-10%.1 It is predominantly 58 seen among elderly women in their sixth to eighth decades of life.1,2 80% of XGC cases are 59 associated with gallbladder calculi. The association between XGC and gallbladder carcinoma is 60 doubtful, although some studies in the literature reported gallbladder carcinoma in 8.5% to 61 30.5% of XGC cases.1 Accompanying bacterial infections can also be identified and commonly 62 isolated organisms are Escherichia coli, Klebsiella and Enterococcus.2 One third of XGC cases 63 are associated with complications such as perforation, abscess and fistula formation, 64 inflammatory infiltration to adjacent structures including the liver, colon and abdominal wall.1,2 65 The clinical presentation of XGC is variable and non-specific.1 Majority of the patients present 66 with right upper quadrant pain and features of chronic cholecystitis. On examination, right upper 67 quadrant tenderness and palpable mass can be seen. No specific laboratory test is available for 68 XGC.2 Elevated leukocytes level is usually present. Some XGC cases may show elevated tumor 69 marker levels like CA 19-9 and CEA.2,4 70 71 Radiological images play a key role in the diagnosis of XGC, although sometimes the 72 radiological diagnosis of XGC can be difficult due to overlapping features with other 73 conditions.2,4 Ultrasound (US) examination may show significant focal or diffuse gallbladder 74 wall thickening with associated calculi or sludge.1,3 Presence of hypoechoic nodules within 75 thickened wall is a typical finding which favors the diagnosis of XGC.1 Rana et al studied 76 features of GB wall thickening in US which help to differentiate between XGC and gall bladder 77 carcinoma. Presence of focal wall thickening, wall disruption and indistinct liver margin favors 78 underlying neoplastic process compared to diffuse wall thickening or intramural features 79 including echogenic foci and hypoechoic nodules which favors benign process like XGC.8 The 80 most common CT finding of XGC is diffuse gallbladder wall thickening with presence of 81 intramural hypodense nodules or bands and luminal surface enhancement with continuous 82 mucosal line.3,4,5 Goshima et al found that five CT findings improve the sensitivity and 83 diagnostic accuracy for XGC which help to differentiate it from gallbladder carcinoma.5 Those 84 include the above-mentioned CT findings in addition to absence of intrahepatic bile duct 85 dilatation and hepatic invasion.1,5 Kobayashi et al developed a scoring system of five CT 86 components to improve the diagnostic sensitivity and specificity of XGC. It includes diffuse wall 87 thickening of gallbladder, presence of intramural nodules or bands, absence of polypoid lesions, 88 pericholecystic infiltration and pericholecystic abscess. They concluded that presence of three or 89 more findings have high specificity of 94% and sensitivity of 77% for the diagnosis of XGC.4 90 CT may also show associated findings like cholelithiasis and choledocholithiasis along witwall h 91 possible associated previously mentioned complications.3,4,6 CT findings of the current patient ( 92 Figure 1) show comparable findings including irregular diffuse gallbladder mural thickening 93 along with few hypoattenuating mural nodules, multiple hyperdense calculi, pericholecystic fluid 94 collection and choledocholithiasis. Poor fat planes to the adjacent liver parenchyma is also noted. 95 96 MRI usually demonstrates findings similar to the CT scan.1 Signal drop-out in In-phase and 97 Opposed-phase chemical shift imaging denoting the presence of microscopic fat within the 98 thickened gallbladder wall is considered a characteristic finding of XGC.3 Diffusion weighted 99 imaging has an additive value which helps to further discriminate between XGC and gallbladder 100 carcinoma. Majority of gallbladder carcinomas show diffusion restriction compared to only 7% 101 of XGC cases.3,5,7 MRI of the current patient ( figure 2) shows a diffusely thickened gallbladder 102 wall along with few mural nodules within the thickened wall some of which demonstrate signal 103 drop-out in opposed-phase images (OP) denoting microscopic fat depositions of 104 xanthogranuloma. In postcontrast images, smooth luminal surface enhancement and focal area of 105 early enhancement of adjacent liver parenchyma is noted. No evidence of diffusion restriction 106 was seen. 107 108 Carcinoma of the gallbladder and gallbladder actinomycosis are the most challenging differential 109 diagnosis for XGC and the radiological diagnosis can be difficult due to overlapping features.1,2 110 Fine needle aspiration cytology (FNAC) or biopsy can be helpful preoperatively for further 111 differentiation.2 The systemic review shows that FNAC was an efficient and safe method for 112 diagnosis of gallbladder carcinoma with high sensitivity, specifity and low complication rate. 113 Percutaneous biopsy is un common minimally invasive procedure which can be helpful to 114 diagnose the unresectable cases, however it can be rarely associated with such complications like 115 hemorrhage, bacteremia, bile leakage and peritonitis and tumor seeding. False negative results 116 can occurred especially in small sized lesion.1,2 Adenomyomatosis is another differential 117 diagnosis which is characterized by intramural foci of cholesterol crystals with characteristic 118 reverberation comet tail artefacts on US and “pearl necklace sign” On T2-weighted images.1,3 119 120 Cholecystectomy is the treatment of choice for XGC.2 However, complete removal can be 121 challenging due to extensive adhesions and local inflammatory infiltration.1 A recently published 122 systemic review showed that half of XGC cases required open cholecystectomy and conversion 123 rate was reaching 35%. Although majority of these surgeries were complex, the mortality and 124 complication rates were low and found to be 0.3% and 2-6% respectively.9 125 126 XGC is a rare variant of chronic cholecystitis and the diagnosis can be suspected on pre-127 operative imaging in the presence of typical characteristic imaging findings. However, some 128 cases can be misleading due to overlapping features with other conditions. Sometimes, FNAC is 129 helpful in pre-operative diagnosis. 130 131 Authors’ Contribution 132 AH collected the clinical and radiological data, reviewed literature and drafted the manuscript. IS 133 supervised the work, selected the representative images and reviewed the manuscript. AK 134 created the idea and reviewed the manuscript. All authors approved the final version of the 135 manuscript. 136 137 References 138 1. Singh VP, Rajesh S, Bihari C, Desai SN, Pargewar SS, Arora A. Xanthogranulomatous 139 cholecystitis: What every radiologist should know. World J Radiol. 2016;8(2):183-191. 140 doi:10.4329/wjr.v8.i2.183 141 2. Rammohan A, Cherukuri SD, Sathyanesan J, Palaniappan R, Govindan M. 142 Xanthogranulomatous cholecystitis masquerading as gallbladder cancer: can it be 143 diagnosed preoperatively?. Gastroenterol Res Pract. 2014;2014:253645. 144 doi:10.1155/2014/253645 145 3. Zhao F, Lu PX, Yan SX, Wang GF, Yuan J, Zhang SZ, Wang YX. CT and MR features 146 of xanthogranulomatous cholecystitis: an analysis of consecutive 49 cases. Eur J Radiol. 147 2013;82(9):1391-1397. doi:10.1016/j.ejrad.2013.04.026 148 4. R, Kobayashi T, Ogasawara G, Kono Y, Mori K, Kawasaki S. A scoring system based on 149 computed tomography for the correct diagnosis of xanthogranulomatous cholecystitis. 150 (2020) Acta radiologica open. 9 151 (4):2058460120918237. doi:10.1177/2058460120918237 152 https://doi.org/10.1177/2058460120918237 5. Goshima S, Chang S, Wang JH, Kanematsu M, Bae KT, Federle MP. 153 Xanthogranulomatous cholecystitis: diagnostic performance of CT to differentiate from 154 gallbladder cancer. Eur J Radiol. 2010;74(3):e79-e83. doi:10.1016/j.ejrad.2009.04.017 155 6. Bo X, Chen E, Wang J, et al. Diagnostic accuracy of imaging modalities in differentiating 156 xanthogranulomatous cholecystitis from gallbladder cancer. Ann Transl Med. 157 2019;7(22):627. doi:10.21037/atm.2019.11.35 158 7. Feng L, You Z, Gou J, Liao E, Chen L. Xanthogranulomatous cholecystitis: experience in 159 100 cases. Ann Transl Med. 2020;8(17):1089. doi:10.21037/atm-20-5836 160 8. Rana P, Gupta P, Kalage D, Soundararajan R, Kumar-M P, Dutta U. Grayscale 161 ultrasonography findings for characterization of gallbladder wall thickening in non-acute 162 setting: a systematic review and meta-analysis. Expert Rev Gastroenterol Hepatol. 163 2022;16(1):59-71. doi:10.1080/17474124.2021.2011210 164 9. Frountzas M, Schizas D, Liatsou E, et al. Presentation and surgical management of 165 xanthogranulomatous cholecystitis. Hepatobiliary Pancreat Dis Int. 2021;20(2):117-127. 166 doi:10.1016/j.hbpd.2021.01.002 167 168 169 170 Figure 1: Contrast enhanced Computed Tomography (CT) scans of the abdomen in axial and 171 coronal views from (A–C) demonstrate irregular diffuse gallbladder mural thickening (red arrows) 172 along with few hypoattenuating mural nodules (white head arrows). Multiple hyperdense calculi 173 (white arrows) and pericholecystic fluid collection (yellow arrows) are seen. Poor fat planes to the 174 adjacent liver parenchyma is noted (blue arrows). 175 176 A C 177 178 Figure 2: Magnetic Resonance imaging (MRI) of the abdomen from (A–D) including T2W image 179 (A), In-phase (IP) (B), Opposed-phase (OP) chemical shift imaging (C), T1WI post contrast 180 images in axial (D) show a diffusely thickened gallbladder wall along with few non enhancing 181 mural nodules within the thickened wall which showed iso- to slightly hypointense signal on both 182 T1 and T2-wieghted images and (white head arrows) some of which demonstrate reduced signal 183 in opposed images (OP) denoting microscopic fat depositions of xanthogranuloma (red arrows). 184 Minimal pericholecystic fluid. smooth luminal surface enhancement is noted in post contrast 185 images (blue arrows). Focal area of early enhancement of adjacent liver parenchyma is seen (green 186 arrows). 187 B D