Ovarian cancer spreads along the peritoneum or metastasizes through the blood or lymphatic stream. According to the large autopsy studies in ovarian cancer patients, common sites of metastases include the peritoneum, abdominal lymph nodes, bowel, liver, and lung, whereas the bile duct was not recognized as a metastatic site [6] [3]. The bile duct is suggested as an extremely rare site of ovarian cancer-associated metastases, as there are no previously reported cases in the literature.
Although rare, several cases of metastatic malignant tumor involving the bile duct have been reported. Intrabiliary growth of metastatic carcinoma was first reported in 1946 with symptomatic jaundice, biliary dilatation, and cirrhosis on autopsy [7]. Reported metastases to the bile duct include primary cancers of the colon, lung, breast, gallbladder, testicle, or pancreas [8]. The predominant primary lesions were colorectal carcinoma and the incidence of intrabiliary metastasis was reported as 3.6% in metastatic colorectal cancer [9]. Intrabiliary metastasis is extremely rare in non-colorectal tumors and its incidence was reported at 0.7% [9].
Several mechanisms for the intrabiliary growth of metastatic tumors have been suggested. Metastasis to the liver parenchyma through intrabiliary growth is suggested in colorectal cancer. Kubo et al. reported that macroscopic intrabiliary extension was observed in 10.6% of colorectal liver metastases. They also reported that in 3.7% of the cases, tumor formation was not observed in the liver parenchyma but only in the bile duct. As another mechanism, the peribiliary capillary plexus, which connects the portal vein or hepatic arteries, may help cancer cells metastasize to the bile duct via the blood stream [10]. In colorectal cancer, mucosal colonization in the biliary epithelium was commonly observed in intrabiliary metastasis [9]. Intraductal growth exhibits intraluminal expansion without dysplastic change in mucinous epithelium [11]. Further, cholangiocarcinoma spreads along epithelial surfaces with dysplastic changes around the tumor, which are well known as precursors of cholangiocarcinoma.
Imaging findings of intrabiliary metastasis mimic primary cholangiocarcinoma, and high-attenuation intraductal masses are regarded to be indistinguishable from the primary biliary malignancy [12] [13] [14]. When an intrabiliary tumor is found in patients with other malignant disease, diagnostic confusion with primary cholangiocarcinoma can occur. In this case, IDUS and CT showed an intraductal mass located at the hepatic hilum. Peritoneal dissemination and lymph node metastasis were not observed around the common bile duct. Tumor biopsy and brush cytology were suggested to be of benefit for a definite diagnosis of metastatic carcinoma [11]. However, in this case, preoperative endoscopic biopsy of the tumor showed atypical cells and did not provide a definite histopathological diagnosis. As cytologic or systemic diagnosis obtained during endoscopic retrograde cholangiopancreatography (ERCP) has low sensitivity, it is difficult to diagnose malignant etiologies of biliary strictures [15].
In this case, we performed a right hepatectomy with caudate lobectomy and extrahepatic bile duct resection, which is relatively invasive and can cause life-threatening complications. When she was diagnosed with a hepato-hilar bile duct tumor, recurrent peritoneal metastasis of ovarian cancer was also detected. The optimal treatment for metastatic ovarian cancer of the bile duct would be chemotherapy. However, in this case, we could not obtain a definite histopathological diagnosis preoperatively. In general, both paclitaxel and carboplatin are not effective in cholangiocarcinoma. There was concern that the tumor was a primary cholangiocarcinoma and these anticancer drugs would not be effective, resulting in a loss of opportunity for curative treatment. In this case, because infiltration to the right hepatic artery was suspected, the preoperative staging of the hepato-hilar tumor was estimated as stage IIIA by International Union Against Cancer (UICC) staging for perihilar cholangiocarcinoma. The overall 5-year survival rate after surgery in stage IIIA hilar cholangiocarcinoma is reported to be approximately 45% [16], whereas the 5-year survival rate of advanced ovarian cancer (FIGO Stage III/IV) is reported to be approximately 30% [17]. Surgical resection for cholangiocarcinoma was therefore selected as the optimal treatment.
In the resected specimen, the tumor was mainly located at the bifurcation of the common hepatic duct, and invasion to the liver parenchyma was not observed microscopically. Immunohistochemical staining was positive for CK-7 and WT-1, and negative for CK-20, suggesting that the tumor was not bile duct cancer but metastasis from ovarian serous adenocarcinoma [18]. The tumor extended to the subserosal layer of the hepatoduodenal ligament. However, direct exposure to the hepatoduodenal ligament was not detected histopathologically. Although a microscopic peritoneal metastasis was found at the hepatoduodenal ligament, this small tumor did not invade the bile duct and was completely separate from the tumor at the hepatic hilum. Finally, the patient was diagnosed with intraductal metastasis from ovarian cancer.
In conclusion, this is a rare case of ovarian cancer metastasis mimicking hilar cholangiocarcinoma at the bifurcation of the common hepatic duct. Whereas it is difficult to distinguish primary bile duct carcinoma from other metastatic disease, a correct diagnosis may be possible by considering the possibility of metastatic ovarian cancer and comprehensive evaluation of the medical history and the histological features.
