The Great Imitator: A Case Report of Mirizzi Syndrome Misdiagnosed as Cholangiocarcinoma Bismuth Type II

Abstract

Background

An unusual complication of gallstone diseases is Mirizzi syndrome. This disorder is characterized by jaundice, fever and right upper quadrant pain. It is defined by an obstruction of the common hepatic duct due to an extrinsic compression from a stone in the gallbladder infundibulum or the cystic duct. It should be identified as soon as possible in order to prevent complications, notably biliary sepsis.

This disorder can sometimes mimic the symptoms of cholangiocarcinoma (CCA).

Case summary

We present the case of a 69 years old male presenting for painless jaundice and dark urine of 1 week duration. Upon several abdominal imaging and laboratory examinations, the patient was diagnosed with CCA Klatskin tumor type II. The patient was referred for a bile duct resection with caudate lobectomy and Roux-en-Y hepticojejunostomy. However, during surgery, the patient was found to have 2 large stones at the base of gallbladder, obstructing the common bile duct, directing the diagnosis towards Mirizzi syndrome (MS).

The uniqueness of the case lies in the patient’s presentation, as well as the thorough investigation which were in favor of the Klatskin tumor.

Conclusion

MS is a very rare complication of gallstone diseases. It can sometimes present similarly to CCA. Therefore, a more precise and accurate diagnostic tools should be employed in order to be able to differentiate between these two entities.

Learning Points

• What initially presented as a Klatkin tumor due to obstructive jaundice, proximal bile duct wall thickening, and increased metabolic activity on PET scan was found to be a case of Mirizzi syndrome after intraoperative assessment and negative histological biopsies.

• This could be explained by the fact that as advanced cases of Mirizzi syndrome can cause inflammation induced changes leading to wall thickening and fibrosis, which may mimic neoplastic processes.

• The significance of this case lies in highlighting the diagnostic challenges in recognizing Mirizzi Syndrome due to the overlapping clinical and radiologic features with a Klatskin tumor and emphasizing the necessity of maintaining a high clinical index of suspicion and a broad differential diagnosis in such presentations.

Introduction

Mirizzi syndrome (MS) is a rare complication of a long-standing cholelithiasis, in which a gallstone migrates towards Hartmann’s pouch or the cystic duct, therefore compressing the common hepatic duct and sometimes leading to cholecystobiliary fistula.^1,2 It presents with right upper quadrant pain, jaundice and cholestatic liver enzyme abnormalities, closely resembling other hepatobiliary disorders such as cholangiocarcinoma (CCA).^2,3 Although very rare, early recognition of Mirizzi syndrome is crucial as it can progress to biliary sepsis.^4,5

Case Description

This is the case of a 69 years old male patient, known to have hypertension and BPH, presenting for 1 week history of painless jaundice accompanied by dark urine and clay colored stool. The patient reports that his urine turned dark 3 days prior to onset of jaundice.

He denied any other urinary and abdominal symptoms. The physical exam was negative for any suprapubic, costovertebral or abdominal pain. Initial laboratory testing demonstrated a cholestatic pattern of liver injury. Total bilirubin was 12.4 mg/dL (reference: 0.2–1.2 mg/dL) with direct bilirubin 9.8 mg/dL. Alkaline phosphatase (ALP) was 612 IU/L (reference: 40–129 IU/L), gamma-glutamyl transferase (GGT) 784 IU/L (reference: <60 IU/L), aspartate aminotransferase (AST) 146 IU/L (reference: <40 IU/L), and alanine aminotransferase (ALT) 172 IU/L (reference: <41 IU/L). Inflammatory markers were mildly elevated with C-reactive protein (CRP) 28 mg/L and white blood cell count 11.8 ×10⁹/L. This biochemical profile was consistent with obstructive cholestasis, supporting the radiologic suspicion of a proximal biliary obstruction.

Initially, computed tomography (CT) scan of the abdomen showed a distended gallbladder with enhancing and thickened walls without any visible gallstones. Moreover, mild dilation and enhancement of the intrahepatic duct with a tortuous, dilated and enhancing proximal ducts, close to the confluence was noted. There was no evidence of common bile duct dilation (Figures 1 & 2).

Figure 1.

CT scan showing dilatation of the cystic duct (red arrow) and common hepatic duct (yellow arrow) with mild peri-portal edema (blue arrow)

Figure 2.

CT scan showing distention of the common hepatic duct (blue arrow) and cystic duct (red arrow) showing slightly thickened and enhanced walls

After CT scan, multiplanar multisequence magnetic resonance imaging (MRI) of the abdomen with IV gadolinium, as well as magnetic resonance cholangiopancreatography (MRCP) were done to rule out any underlying process as clinically warranted. Diffusion-weighted imaging (DWI) sequences were not included in the MRI protocol. While DWI can provide adjunctive information in differentiating malignant from inflammatory biliary wall thickening, its absence represents a limitation in the preoperative radiologic assessment of this case. MRI demonstrated circumferential enhancing wall thickening of the proximal common hepatic duct extending up to the level of the ductal confluence. The confluence of the right and left hepatic ducts appeared narrowed but without definite extension into either the right or left hepatic duct branches. No segmental ductal involvement beyond the confluence was identified. Based on involvement reaching the biliary confluence without extension into secondary ducts, the lesion was radiologically classified as Bismuth–Corlette type II.

Moreover, inflammatory changes were noted among the cystic duct draining of the level of the common hepatic duct, distal intrahepatic ducts and gallbladder denoted by increased wall enhancement, gallbladder wall thickening and pericholecystic fat stranding.

Few filling defects were also present in the gallbladder neck, likely representing biliary sludge (Figure 3).

Figure 3.

3D MRCP in the coronal plane showing intrahepatic bile duct dilatation (yellow arrow), filling defect in the proximal common hepatic duct (green arrow), compared to normal distal common bile duct (red arrow)Blue arrow: Cystic Duct; Orange Arrow: Intrahepatic ducts

In addition, there was mild bilateral intrahepatic biliary ductal dilatation, without any evidence of acute cholecystitis.

These findings are in favor of Klatskin tumor type II associated with proximal mild intrahepatic biliary ductal dilatation and sludge within the dilated cystic duct inserting in the common hepatic duct.

Positron emission tomography (PET) scan of the abdomen displayed an increased activity at the level of the proximal common bile duct with SUV max 6.6, further supporting the suspicion of Klatskin tumor seen on MRI (Figure 4).

Figure 4.

PET scan showing an increased activity at the level of the proximal common bile duct

Although endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are commonly employed in the evaluation of indeterminate hilar strictures, these modalities were not pursued preoperatively in this case. Cross-sectional imaging (CT, MRI/MRCP) demonstrated a radiologically resectable hilar lesion without evidence of distant disease, and positron emission tomography computed tomography (PET-CT) showed focal hypermetabolic activity (SUVmax 6.6), further supporting the working diagnosis of Bismuth-Corlette type II hilar CCA(Figure 5).

Figure 5.

Intraoperative figure demonstrating the evacuated stones at the level of the gallbladder base obstructing the common bile duct

In potentially resectable hilar CCA, routine preoperative biliary instrumentation is often avoided due to the risks of cholangitis, post-ERCP pancreatitis, and possible tumor seeding, particularly when imaging findings are strongly suggestive and surgical exploration is planned upfront. Current consensus guidelines indicate that tissue confirmation is not mandatory prior to surgery in cases with high radiologic suspicion of resectable perihilar CCA. ⁶

In retrospect, preoperative ERCP or EUS-guided evaluation might have demonstrated extrinsic compression or cystic duct stones, potentially clarifying the diagnosis.

Based on the abdominal imaging and the conclusive diagnosis of Klatskin tumor, the patient was bound to undergo a bile duct resection with caudate lobectomy and Roux-en-Y hepaticojejunostomy.

During laparoscopy, the gallbladder appeared markedly inflamed and fibrotic, with dense adhesions to the anterior abdominal wall and duodenum. The cystic duct–common hepatic duct junction was indurated, raising concern for infiltrative malignancy. Frozen sections were obtained from the gallbladder wall, the cystic duct margin, the proximal common hepatic duct and the fibrotic tissue at the hepatoduodenal ligament. All frozen sections were negative for dysplasia or malignancy and demonstrated only chronic inflammatory changes with fibrosis.

Given the absence of histologic confirmation of malignancy and the intraoperative finding of a necrotic cystic duct pedicle harboring two impacted calculi compressing the common hepatic duct, the operative plan was modified. Radical oncologic resection with caudate lobectomy was abandoned, and the diagnosis was revised intraoperatively to MS (Csendes type I). A T-tube was placed following stone extraction and bile duct exploration.

Despite radiologic and clinical features suggestive of a Klatskin tumor, definitive intraoperative assessment revealed pathology consistent with MS.

Discussion

MS is a rare complication of cholelithiasis that occurs due to the extrinsic obstruction of the common hepatic duct by a gallstone found either in the cystic duct or in Hartman’s pouch.^1,4 The Csendes classification delineates MS into four subtypes based on the extent of biliary involvement: Type I lesions are those causing an external compression of the common bile duct. In Type II lesions, a cholecystobiliary fistula is present and erodes less than one-third of the circumference of the bile duct. In Type III lesions, the fistula involves up to two-thirds of the duct circumference and in Type IV lesions there is a complete destruction of the bile duct. ²

Clinically, patients usually present with obstructive jaundice, dark colored urine, clay colored stools, right upper quadrant (RUQ) pain and bile duct dilation on imaging.^2,3 The initial imaging modality is a RUQ ultrasound. If the findings show a suspected stone in the common bile duct, MRCP is the imaging of choice.^5,6 Note that no abdominal ultrasound was done in our case. However, the gold standard remains the ERCP as it permits a clear visualization of both the biliary tract and the cholecystobiliary fistulas if present. ⁷ Management is surgical and depends on disease severity. If mild (Type I), a laparoscopic cholecystectomy is indicated. For severe cases (Types II-IV), surgeries can range from partial cholecystectomies to biliary duct reconstruction or hepaticojejunostomy. ³

It is important to note that despite its rarity – with an occurrence of 0.1% in patients with gallstones, MS often presents with nonspecific symptoms that can overlap with other obstructive conditions, posing significant diagnostic challenges. ⁵ Therefore, even if considered as an uncommon complication of cholelithiasis, it is essential to consider it in the differential diagnoses.

One of the MS mimicking lesions is the Klatskin tumor, a type of CCA accounting for 10-20 % of the total intrahepatic disorders. ⁸ It is found within 2 cm of the junction of the right and left hepatic duct at the hepatic hilum. ⁹ It is categorized into several types,following the Bismuth-Corlette classification:

Type I are the tumors found below the convergence of the left and right hepatic ducts. If the tumor reaches only the junction of the hepatic ducts it is considered as a Type II. Tumors obstructing the common hepatic duct and either the right or left hepatic duct are classified as Type III and multicentric tumors that involve the convergence and the right and left hepatic ducts are Type IV tumors. ⁶ It can also present with jaundice, pruritus, dark urine, clay-colored stool, abdominal pain and weakness. It is diagnosed by CT scan and can appear as a hyper attenuating intraductal mass with mural thickening, lumen obliteration at the hilar bile duct causing intrahepatic biliary radical dilatation. MRCP can also be used.^8,9 Also, a biopsy of a presumed CCA is not recommended as it might increase the risk of tumor seeding. ⁹ According to the Bismuth–Corlette classification, type II tumors involve the hepatic duct confluence without extension into the right or left secondary ducts. In our case, the lesion demonstrated circumferential narrowing up to the confluence without clear lateral ductal extension, fulfilling radiologic criteria for type II classification. However, this case illustrates how inflammatory compression at the cystic duct–common hepatic duct junction may simulate confluence involvement and potentially lead to overclassification.

Cross-sectional imaging plays a central role in differentiating MS from hilar CCA; however, significant overlap exists. In MS, typical findings include: Impacted stone in the cystic duct or gallbladder neck, extrinsic compression of the common hepatic duct, inflammatory wall thickening and pericholecystic fat stranding. Conversely, hilar CCA more commonly demonstrates: Irregular asymmetric ductal wall thickening, abrupt ductal cutoff, delayed contrast enhancement and absence of gallstones.

In our case, circumferential proximal duct wall enhancement and focal fluorodeoxyglucose (FDG) uptake favored malignancy, while subtle pericholecystic inflammatory changes and cystic duct filling defects were retrospectively suggestive of MS.

MRCP is highly sensitive for detecting biliary strictures but cannot reliably distinguish inflammatory from neoplastic wall thickening. CT similarly lacks specificity in differentiating fibrosis from tumor infiltration. PET-CT, although useful for staging, is limited by false-positive uptake in inflammatory conditions. These limitations underscore the importance of integrating imaging pattern recognition with clinical and biochemical findings and maintaining suspicion for inflammatory mimickers of malignancy.^9-11

Despite ongoing advances in CT, MRCP, PET-CT, and endoscopic imaging techniques, differentiating inflammatory biliary strictures from hilar cholangiocarcinoma remains difficult and highly operator-dependent. Accurate interpretation requires close multidisciplinary collaboration among radiologists, gastroenterologists, and hepatobiliary surgeons. ⁹ Emerging artificial intelligence (AI)-assisted imaging analysis and radiomics may further improve diagnostic precision in the future by identifying subtle imaging patterns that are not readily apparent on conventional assessment. Nevertheless, even when preoperative imaging favors Mirizzi syndrome, underlying cholangiocarcinoma cannot always be definitively excluded. Consequently, intraoperative exploration and frozen section analysis continue to play a critical role in establishing the final diagnosis and guiding the extent of surgical resection. ¹⁰

Thus, in our case what initially presented as a Klatskin tumor due to obstructive jaundice, proximal bile duct wall thickening, and increased metabolic activity on PET scan was found to be a case of MS after intraoperative assessment and negative histological biopsies. False-positive FDG uptake on PET-CT in biliary inflammatory conditions has been well documented. Active inflammation results in increased glucose metabolism due to macrophage and neutrophil activation, leading to increased FDG accumulation that may mimic malignancy. In MS, impacted stones and cystic duct necrosis can generate intense periductal inflammation and fibrosis, producing focal hypermetabolic activity indistinguishable from CCA on PET imaging. Similar observations have been reported in inflammatory biliary conditions mimicking both MS and hilar malignancy. ¹⁰ This pathophysiologic mechanism likely explains the SUVmax of 6.6 observed in our patient. This could be explained by the fact that as advanced cases of MS can cause inflammation induced changes leading to wall thickening and fibrosis, which may mimic neoplastic processes. ³

Conclusion

The significance of this case lies in highlighting the diagnostic challenges in recognizing MS due to the overlapping clinical and radiologic features with a Klatskin tumor and emphasizing the necessity of maintaining a broad differential diagnosis in such presentations.