Intrabiliary Metastasis of Colon Cancer Mimicking Cholangiocarcinoma and Chemotherapy-Induced Sclerosing Cholangitis: A Case Report

Introduction

Intrabiliary metastasis of colon cancer without involvement of the hepatic parenchyma is rare (1). Metastases to the liver can cause biliary obstruction and result in painless jaundice, pale stools, dark urine, and pruritis, and such metastases are associated with elevations of direct bilirubin and alkaline phosphatase (2). In addition, imaging findings showing such metastases as mimicking sclerosing cholangitis as a multifocal biliary stricture are rare. Here, we report a case of intrabiliary metastasis of colon cancer and the associated imaging findings.

Case Presentation

An 82-year-old man presented with colon metastasis after right hemicolectomy and while undergoing chemotherapy. Laboratory tests at regular follow-up revealed elevated CA19-9 and CEA. Computed tomography (CT) was performed, which revealed soft tissue density in the common bile duct (CBD) and right intrahepatic duct (IHD) with wall thickening, resulting in biliary dilatation (Figures 1 and 2). Percutaneous transhepatic cholangiography and drainage (PTCD) was performed, and cholangiography revealed multiple strictures of the intrahepatic and extrahepatic bile ducts, causing obstructive jaundice (Figure 3). Based on his history and radiological findings, the differential diagnosis included metastasis, chemotherapy-induced sclerosing cholangitis (CISC), and cholangiocarcinoma. Cytology of bile collected from the percutaneous transhepatic drainage tube revealed no features of malignancy. CT-guided biopsy was then performed and revealed high-grade atypical glands. Immunohistochemical study revealed that the atypical glands were CK7(−), CK20(+), and CDX-2(+) (Figure 4).

According to the study result, metastatic adenocarcinoma would be considered first rather than biliary duct primary malignancy given the absence of CK7 expression. The patient’s condition was poor, total bilirubin levels increased again, and liver function worsened, requiring the insertion of two PTCDs on each side. One month later, septic biliary tract infection exacerbated progressively, and the patient finally died.

Discussion

In our case, CT and cholangiography revealed wall thickening of the extrahepatic and intrahepatic bile ducts accompanied by stricture and dilatation. Our case also presented the imaging findings of biliary obstruction and biliary stricture, which are also the imaging findings for secondary sclerosing cholangitis and primary cholangiocarcinoma. CISC has been reported to be occasionally caused by hepatic arterial infusion chemotherapy with fluoropyrimidines (3–5). In the study, considering the sudden onset of bile duct lesion during chemotherapy (FOLFOX4), as sclerosing cholangitis was suspected, the patient received initial treatment with steroids, and the chemotherapy was discontinued. However, rapid elevated tumor markers (CEA: 171 ng/mL, CA19-9: 10115 U/mL) and no improvement after cessation of chemotherapy were noted. Distinctive findings of sclerosing cholangitis, such as “onion skin” fibrosis (6) around the bile duct, were not found in the liver biopsy in our case. Cholangiocarcinoma has the following morphology and growth patterns: mass formation, periductal infiltration, and intraductal growth (7). The imaging findings of intraductal and periductalinfiltrating type of cholangiocarcinoma included biliary strictures, intraductal neoplasms, and focal or diffuse ductal thickening with or without enhancement (8, 9). Differentiating intrabiliary colorectal liver metastases from primary intrahepatic cholangiocarcinoma is difficult. However, immunohistochemical studies, such as CK7, CK20, and CDX2 staining, can provide the definite diagnosis (10). Metastatic colon carcinoma shows CK20 positivity and CK7 negativity in contrast to the adjacent bile duct epithelium, which is CK7-positive and CK20- negative (11). In our case, no CK7 expression was found. According to the result, metastatic adenocarcinoma would be considered first rather than primary biliary duct malignancy. In our case, imaging studies revealed obstructive jaundice without an intraparenchymal mass. Biopsy techniques for intrabiliary lesions include brush cytology, clamshell forceps under choledochoscopic guidance, and clamshell forceps under fluoroscopic guidance. In a previous study, the choledochoscope-directed biopsy technique had highest sensitivity and specificity, but this difference was not statistically significant (12). However, in this study, the patient refused to accept endoscopic retrograde cholangiopancreatography (ERCP), and clamshell forceps were not available in our hospital; thus, we performed transhepatic biopsy. Because ductal thickening with soft tissue density cannot be well identified under sonography, real-time USG combined with CT is useful for localizing inconspicuous focal hepatic lesions (13). The etiology of intrabiliary growth of liver metastasis is unknown, but the etiology probably involves vascular invasion or the implantation of malignant cells in the biliary epithelium through bile flow (14). Patients with intrabiliary metastasis have better prognosis than patients without metastasis; moreover, patients with macroscopic involvement have a much higher 5-year survival rate (80%) than those with microscopic involvement (15). However, the condition of our patient was poor, his total bilirubin levels increased again, and his liver function worsened, even after two PTCDs were inserted on both sides; consequently, the patient was transferred to the hospice ward and died 1 month later.

Conclusion

In conclusion, intrabiliary metastasis is easily overlooked. An immunohistochemical study is helpful to achieve the correct diagnosis and management.