A case of biliary cystic tumor with repeated hemobilia

Discussion

Hemobilia was first reported by Sandblom in 1948. It is a rare condition often caused by trauma, iatrogenic events, cholangitis, or cholelithiasis [1], but rarely by neoplasms (5% to 6% of all cases) [4]. Its symptom is known as the trilogy of Quincke, upper gastrointestinal hemorrhage, epigastralgia, and jaundice. When the biliary tract is obstructed by blood clots, abdominal pain and jaundice occur because of increased pressure in the tract. In the presented case, our patient experienced abdominal pain, but not jaundice, and her laboratory results indicated anemia with abnormal liver function.

Angiography is recommended for the examination and treatment of uncontrolled hemobilia [5]. If hemorrhage occurs from an artery, TAE is the first choice of treatment and often effective. Although our patient was successfully treated with TAE for the six hemobilia episodes during her 8-year hemangioma follow-up, hemorrhage recurred frequently, and the tumor was growing. She therefore underwent surgical intervention and was finally diagnosed with IPNB and an associated invasive carcinoma.

Common symptoms and complications of IPNB are abdominal pain, liver function disorder, jaundice, or fever caused by the bile duct obstruction due to hypersecretion of mucin or the tumor itself [6,7]. We could not find a previous report of hemobilia caused by IPNB by searching MEDLINE using the English language. Sugawara et al. suggested that the risk of hemobilia from neoplasms depended on tumor size and histological type, especially in cases of soft and fragile papillary tumors [8]. Biliary cystic tumors are rare neoplasms occurring in the liver and, less frequently, the extrahepatic biliary system [2]. They account for less than 5% of all reported cystic lesions of the liver [9].

According to the 2010 WHO Classification of Tumors of the Digestive System, biliary cystic tumors are no longer defined as biliary cystadenoma, papillomatosis, papillary adenocarcinoma, or biliary cystadenocarcinoma, but instead are redefined as IPNB and MCN of the liver [3]. IPNB is identified as a premalignant lesion or intraepithelial neoplasm of the bile duct and divided into intraductal papillary neoplasms with low-, intermediate-, or high-grade intraepithelial neoplasia, according to tumor cell grade [7,10]. Papillary tumors of the bile duct are relatively rare with a reported prevalence of 4% to 15% among all bile duct cancers [11-13]. On the other hand, MCN of the liver is the biliary counterpart of pancreatic MCN. The disease usually occurs in women and does not exhibit a luminal communication with the pancreatic or bile ducts [14]. MCN also differs from IPNB with respect to the expression of estrogen and progesterone receptors, owing to the presence of a subepithelial ovarian-like stroma in the former. In this case, the intrahepatic bile ducts were markedly dilated with papillary proliferation in the lumen, and the tumor cells exhibited marked atypical appearance. Ovarian-like stroma was not identified. Thus, our final diagnosis was IPNB with an associated invasive carcinoma.

Ogawa et al. reported several CT findings of IPNB [15], including the presence of intraductal mass, extensive infiltration along the bile duct, intense enhancement rim at the base of the mass, and isodense or hyperdense lesions relative to the normal hepatic parenchyma during the late arterial phase. In our case, the tumor was enhanced from the portal to the venous phase with obstruction of the right hepatic bile duct. Although hemangioma, which was our preoperative diagnosis, could also exhibit a tendency of volume increasing and contrast enhancement as a result of bleeding, the resected tumor in this case presented as a multilocular cyst filled with multiple yellowish papillary nodules, hypersecretion of clear mucin, and granular mucosa growing directly into the bile duct lumen. As also observed in IPMN-P, columnar and cuboidal tumor cells of IPNB have papillary or villous structures and show expansive growth into the lumen of the bile duct with fibrous vascular stroma.

The CT findings in our case showed well-enhanced massive papillary contents in the dilated bile ducts with extravasation. The intraductal papillary contents evident by contrast CT further indicated that the tumor was present in the bile ducts instead of the liver parenchyma. Moreover, the repeated hemobilia episodes were also indicative of the bile ducts' involvement.

IPNB are recognized as slow-growing neoplasms compared to normal intrahepatic bile duct carcinoma [16]. Several articles present and recommend radical surgical management as the first choice of treatment for IPNB [6,17], with a reported 5-year survival rate after radical surgery ranging from 31% to 80% [18]. But in a latest big study, Kubota et al. reported better prognosis of resected IPNB [7]. They emphasize the necessity of complete resection, and the 1-, 3-, 5-, and 10-year overall survival rates for the 105 mucin-producing IPNB patients were 96%, 90.4%, 84%, and 81.1%. If a recurrent tumor is present, radical surgical therapy must be planned owing to its slow growing characteristic [6].

In this case, only the lateral lesion was resected for diagnostic purposes in the initial surgery, owing to the lack of any malignant impression. The residual lesion in the right lobe showed slow progression, with repeated hemobilia. IPNB also exhibits slow clinical progression, despite the possibility of direct invasion to the bile duct, leading to its dilatation, jaundice, or hemobilia.