Intrahepatic bile duct cystic tumors (IBCTs) are a relatively rare type of cystic tumor of the liver; the etiology of which is still unknown and reported to account for 5% of all intrahepatic cystic diseases, With a better understanding of IBCTs and advances in imaging techniques, they are increasingly reported; however, their actual incidence should be higher because they are commonly misdiagnosed as simple liver cysts or other cystic lesions. Most of the lesions are solitary, mostly in the intrahepatic bile ducts and rarely in the extrahepatic bile ducts or the gallbladder, and most of the cysts are not identical to the bile ducts. IBCTs can be divided into two histological types: IBC and intrahepatic biliary cystadenocarcinoma (IBCA) [4, 5]. IBC is a precancerous lesion with a malignant rate of up to 30%. Based on the nature of the lining epithelial envelope, they can be classified as mucinous and plasmacythematous and mixed cystadenomas. In 1985, Emer defined cystadenoma of the intrahepatic bile ducts as an intrahepatic multi housed lesion with ovarian-like mesenchymal lining. However, some cystadenoma specimens were not found to have ovarian-like mesenchyme in clinical practice. Only two of the four female patients with biliary cystadenoma in our group had pathological findings of ovarian-like mesenchyme.
The symptoms and signs of patients with IBC are mostly atypical and related to tumor size and location. When compressing the surrounding tissues or blocking the bile duct, abdominal discomfort or pain may appear, and jaundice may appear when compressing the bile duct. If the tumor ruptures with abdominal or internal bleeding, the patient may show acute abdomen. In a few cases, the combination of bile duct stones, pancreatitis, liver abscess, etc., may show corresponding symptoms. There are no specific tumor markers in the serological diagnosis of this disease, and the main detectors include CA199, CEA, CA125, and AFP. CA19-9 levels are elevated in 60% of patients with IBC and IBCA. Still, it is not specific, and CA19-9 levels are not significantly correlated with the benignity or malignancy of the lesion[8, 9], but CA19-9 levels in serum and cystic fluid are important for IBCA. Levels have some value in the diagnosis of IBCA. In our group, CA125 and AFP levels were not abnormal in the six patients, while the CA19-9 level was elevated in two cases, in addition to CEA in two other cases. In addition to the role of CA19-9 in identifying cystadenoma, CEA was also found to be valuable in the diagnosis of IBC in this group of cases. IBC has a high rate of misdiagnosis. In addition to the lack of specific clinical symptoms and signs, imaging findings are easily confused with cystic liver lesions, such as simple liver cysts, liver abscesses, liver lymphangiomas, IBCA, and hepatic hydatid cyst. Color Doppler ultrasound showed that the sonogram of the bile duct cystadenoma was a round or oval cystic mass in the liver, with a cystic structure, mostly multilocular, with a clear boundary, a complete capsule, and a uniform thin wall. Most of the inner part was an anechoic zone, and there was a separation zone. If the sound transmission in the capsule was poor, the cyst fluid would be thick, the intracapsular septum thickened, wall nodules larger than 1.0 cm, with large calcification; in such conditions, the possibility of IBCA should be considered. On plain CT scan, single or multiple cystic masses could be seen with septation. After contrast enhancement, the wall and septum of the capsule could be enhanced in different degrees. Since the capsule may contain mucus, serous, bile-stained or brown cloud flocculent liquid, or even cholesterol, necrotic or purulent substances, the density of the same capsule or different capsules may be different.
IBC presents as a cystic occupancy on MRI, and the different fluid components within the cyst determine its signal, which is generally a low signal on T1W1 images and a high signal on T2W1 images. Suppose T1W1 high signal is suggestive of hemorrhagic or cystic fluid hyperprotein. In that case, enhancement scans show frequent enhancement of the cyst wall and compartment, with diminished enhancement in the portal vein and equilibrium phase. IBC shows cystic space-occupying lesions on MRI, and the different fluid components in the cyst determine its signal. Generally, T1W1 has a low signal, and T2W1 has a high signal. T1WI images showing a high signal indicate hemorrhagic or high protein in cyst fluid. The enhanced scan showed that the cyst wall and the separation were often enhanced, and the portal vein and balance phase were weakened. MRI has advantages over CT in judging the shape of the cyst contents; in addition, magnetic resonance cholangiopancreatography (MRCP) can show if the cyst is connected to the bile duct, which helps to formulate a surgical plan.
MRI has an advantage over CT in determining the shape of the cystic contents, and MRCP can detect if the cyst is communicating with the bile ducts, which can help surgical plans[12, 13]. A significant thickening of the partition, papillary protrusions or wall nodules, gross calcification, or intracystic hemorrhage in the sac indicates hepatobiliary cystadenocarcinoma. In addition, PEC-CT helps exclude IBCA[14, 15]. In imaging diagnosis of suspected IBC or IBCA, trans-invasive examination or percutaneous fine-needle aspiration cytology is not recommended. The fluid component characteristics of the lesion have limited diagnostic value in addition to the risk of the risk dissemination along the needle tract. However, it is easy to misdiagnose a simple hepatic cyst for atypical IBC with smooth wall and no excrescences. In addition, a few cystadenomas may also have cyst wall nodules and calcification; therefore, a high index of suspicion as well close follow-up of atypical patients is necessary to prevent delay in treatment.
As early as 1892, Keen first reported the treatment of IBC by hepatectomy. So far, surgical resection is the first choice for the treatment of IBC[16, 17]. Due to the difficulty of the preoperative diagnosis of IBC and the high rate of malignant transformation, it is recommended that a possible diagnosis of IBC be considered in all patients with atypical hepatic cystic diseases. Since the disease is prone to recurrence, the rate of postoperative recurrence in treatment methods, such as fenestration drainage and tumor enucleation exceeds 90%7; thus, the above treatment methods can’t achieve a radical cure. For any suspected IBC to be completely removed, regular hepatic lobectomy should be performed as far as possible to ensure complete resection of the cyst wall and reduction of the recurrence rate. Liver transplantation may be considered in cases where the disease involves the whole liver or incomplete enucleation .For IBC inappropriately treated with fenestration drainage; surgery should be performed as early as possible after functional evaluation. Unfortunately, up to now, a small number of doctors still have an insufficient understanding of IBC. IBC mistakenly underwent fenestration and drainage according to the hepatic cyst, resulting in adverse consequences for patients.
Observing this group of cases found that for patients with IBC, if the cyst wall is thickened during operation, especially for cyst wall with yellow vegetations, the cyst fluid is turbid and flocculent, or a viscous liquid, accompanied by bile-like or dark red bloody fluid, or the shape of the polycystic liver cyst fluid is different, we highly suspect IBC. So, we recommend paying attention to cystic wall morphology and cyst fluid properties during the operation. At the same time, it is recommended that patients diagnosed with liver cysts undergo intraoperative pathological diagnosis and strengthen communication with pathologists to deepen understanding of IBC. It is recommended to perform multiple pathological biopsies or direct liver resection to avoid missing adverse lesions and the possibility of reoperation . Besides, intraoperative pathologic diagnosis is recommended routinely for all liver cyst operations. Owing to the recurrence of IBC, it is recommended that patients undergo examination regularly after the operation. Patients with recurrence can be operated actively, and advanced cases with recurrence and malignant transformation should be treated with radiotherapy, chemotherapy, TKI drugs, or hyperthermic perfusion, which is beneficial in alleviating terminal symptoms[20–22].