Extrahepatic bile duct hepatocellular carcinoma due to recurrence of hematogenous metastasis 50 months after hepatectomy

A 66-year-old man with hepatitis C underwent an extended left hepatectomy for HCC in the medial segment of the liver. Preoperative dynamic computed tomography (CT) and intraoperative evaluation revealed no lymph node metastasis (Fig. 1). Histopathologically, the 3.9-cm-diameter tumor was confirmed to be moderately differentiated HCC with trabecular structure. In addition to microscopic venous invasion, tumor cells had extensively invaded the portal vein, resulting in a tumor thrombus in the left portal vein. There were several daughter nodules of intrahepatic metastasis around the main tumor. Although the resected margin was tumor negative, tumor cells had invaded the serosa of the liver. There was no obvious hepatic artery or bile duct invasion. His postoperative course was good, and his alpha fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) levels were within normal limits. Follow-up CT examinations were performed every 6 months. Fifty months after the hepatectomy, he was referred to our hospital with sudden obstructive jaundice. Laboratory studies revealed hyperbilirubinemia (total bilirubin 10.5 mg/dl) and a slight increase of DCP (85 mAU/ml); AFP levels were normal. CT revealed dilation of the intrahepatic biliary tree, but no definitive mass lesions were found in the liver (Fig. 2a). In addition, there was an aneurysm in the common hepatic artery. Magnetic resonance cholangiopancreatography revealed cholangiectasis from the intrahepatic bile ducts to the middle segment of the common bile duct (Fig. 2b). Wall thickening and a mass showed low signal by T2-weighted imaging and high signal by diffusion-weighted imaging in the middle segment of the common bile duct. Similar to CT, no definitive, hepatic mass lesions were found. Fluorodeoxyglucose positron emission tomography also showed solitary uptake in the middle segment of the common bile duct. Endoscopic retrograde cholangiopancreatography (ERCP) showed that the common bile duct was obstructed by a tumorous lesion covering the upper and mainly the middle segment of the common bile duct (Fig. 2c). Following lesion biopsy, external biliary drainage was performed using an endoscopic nasobiliary drainage (ENBD) tube. After placing the ENBD tube, the patient underwent dynamic liver magnetic resonance imaging. In the dynamic study, the tumor became ambiguous due to the influence of the biliary drainage, and it had poor contrast effect in any contrast phase (Fig. 2d). Cytological examination of the biopsy specimen revealed atypical cells forming papillary arrangement, which was suggestive of cholangiocarcinoma rather than HCC. However, positivity was observed not only for AE1/AE3 but also for Hep par 1. Although it was unclear whether the tumor was cholangiocarcinoma or HCC from these pathological features, the imaging studies suggested that the tumor seemed to develop from the bile duct wall, which implied cholangiocarcinoma rather than HCC. The patient was to undergo surgical resection for diagnostic treatment. Upon selection of the surgical procedure, we considered the pathological findings, patient’s hepatic spare ability, local tumor extent based on ERCP, and common hepatic artery aneurysm that posed a high risk for pancreaticoduodenectomy. Therefore, resection of extrahepatic bile duct and choledochojejunostomy with lymph node dissection were performed on suspicion of solitary cholangiocarcinoma. Complete resection (R0) was achieved by pathologically determining negative surgical margin during surgery.

Macroscopically, an approximately 10-mm-diameter polypoid tumor continuous to the epithelium and a tumor thrombus were found in the dilated common bile duct, and several nodular tumors were observed subepithelially (Fig. 3). The lesions and tumor thrombus were diagnosed as moderately differentiated HCC (Fig. 4a, b). Immunohistochemical staining revealed that they were positive for Hep par 1 (Fig. 4c) and Glypican 3 (Fig. 4d) but negative for both cytokeratin 7 and 20. Moreover, these tumors showed microscopic venous (Fig. 4e) and perineural invasion (Fig. 4f) analyzed using D2-40 and anti-CD31 antibodies. Microsections showed distinct, numerous nodular tumors that were covered by the epithelium and that did not invade the epithelium (Fig. 4a, b). However, the polypoid lesion was not completely covered by the epithelium, protruding toward the lumen of the bile duct with invasion. The tumor thrombus was disconnected to both the tumor and the epithelium. No metastasis was observed in dissected lymph nodes. On the basis of these findings, the patient was diagnosed with recurrent HCC in the extrahepatic bile duct due to hematogenous metastasis. Six months after the surgery, he developed multiple intrahepatic metastases and was still alive at the time of drafting this report.