The simple liver cyst is a type of non-parasitic liver cyst (NPLC). NPLC also includes traumatic liver cysts such as serous hematoma and neoplastic liver cysts such as intraductal papillary neoplasm of the bile duct (IPNB), mucinous cystic neoplasm of the liver (MCN-L), biliary hamartomas, and biliary cystadenoma. Besides, infectious liver cysts, Caroli disease, and Polycystic liver disease (PCLD) are all intrahepatic cystic diseases. Among these diseases, IPNB, MCN-L, biliary cystadenoma, and Caroli disease have been reported to have cancer risk, IPBN and MCN-L are considered precancerous lesions of intrahepatic cholangiocarcinoma(9).
Simple liver cysts are considered to be congenital abnormalities in the development of liver structures. They seem to have an origin over biliary ducts that have not undergone involution, and that by slowly dilating produce the cystic lesions, the cysts do not communicate with the bile duct(10). Reports of malignant transformation of simple liver cysts are infrequent. Azizah, N. and F.J. Paradinas reported two simple cysts and adenocarcinoma cases to coexist closely in the liver, the authors believe that the two patients are cholangiocarcinoma through multi-angle comparison and proposed that cystadenocarcinoma and cholangiocarcinoma coexisting with simple cysts should be treated as two separate concepts. They also cited several other similar cases in the article. Due to the age of publication, it is difficult to determine the specific circumstances of these cases(5). Kokubo, T. et al., and Lee, S.K. et al. respectively reported two cases of intrahepatic cholangiocarcinoma with liver cysts, but these two patients were considered as tumors causing cystic degeneration, which were not the same as the situation in this report(6, 7). A patient-reported by Kaneko, T. et al. was initially diagnosed with a giant liver cyst, the tumor progressed rapidly after puncture and drainage. This case was considered to be a cholangiocarcinoma in the form of a cyst(8). The conditions of the above patients with cholangiocarcinoma all show the characteristics of high correlation with liver cysts, but it is still challenging to determine the occurrence sequence of tumor and cyst.
Our first case had undergone cyst fenestration and drainage for liver cysts. The third year after the operation, a tumor was found at the cyst site where the fenestration was once, and the excised tumor showed cholangiocarcinoma. Another case was found to have liver cysts many years ago and insisted on re-examination. Her condition progressed to a neoplastic lesion within a year. She was diagnosed with cystadenocarcinoma before the operation, and the pathological result was eventually confirmed as cholangiocarcinoma. We have not found similar liver cysts progression reports to intrahepatic cholangiocarcinoma in the available published English literature. Only sporadic reports of other pathological malignancies developed from liver cysts: Hayashi I. et al. showed a mucoepidermoid carcinoma arising from a preexisting cyst of the liver(11), Ameriks J. et al. reported a case of malignant nonparasitic cyst of the liver, but the specific pathological type has not been determined(12), other reports showed that liver cysts can developed into cystadenocarcinoma(13, 14). Besides, Xiao, J. et al. showed a case of hepatic squamous cell carcinoma(SCC) with liver cysts in a study on the liver's primary SCC. In their article, the authors list chronic inflammation of the congenital cysts of the liver cysts associated with infection and/or stones as one of the causes of malignant transformation(15). The continuous stimulation of chronic inflammation leading to malignant transformation may also serve as an explanation for the course of our patients. The lesion may be caused by the constant compression of the cysts on the surrounding bile ducts. Another possible hypothesis is that the tumor originated from the cyst's lining and showed a pattern of intracystic hyperplasia, such cysts may have cellular components derived from the bile duct.
Among the risk factors for the onset of cholangiocarcinoma, the bile-duct cyst is an established high-risk factor(16, 17). Previous studies have shown that choledochal cysts are the most relevant among many high-risk factors for cholangiocarcinoma, The incidence of malignant biliary tumors arising from choledochal cysts ranging from 2.5–26%(17, 18). Reflux of pancreatic enzymes, bile stasis, and increased concentration of intraductal bile acids are thought to play an essential role in the carcinogenesis of the biliary tract(19). This possibility does not seem to exist in our cases. In our cases, the cysts were located at the hepatic hilum's distal end, and there was no prominent bile component. Our cases' condition seems to be more prone to the fact that the bile duct structure's expansion formed the cyst cavity. It can be seen under the microscope that the cysts lining contains bile duct cells; the pathological results of case 2 showed the covered columnar epithelial cells had a minor abnormality. On the other hand, the cysts' long-term stimulation to the surrounding small bile ducts may also lead to carcinogenesis.
The clinical manifestations and laboratory examinations of our case lack specificity, therefore, we believe that the imaging examination has important reference value for discovering the malignant transformation of liver cysts. Doctors should pay special attention to regular review for patients with large volumes, multilocular structures, and multiple cysts. During follow-up, if the cyst is found to be significantly enlarged recently, the thickness of the cyst is uneven, and nodules are found in the cyst wall or inside the cyst,it is necessary to take into account the possibility of malignant cysts.
In conclusion, our cases indicate that liver cysts may deteriorate into intrahepatic cholangiocarcinoma. Patients with multiple liver cysts, giant liver cysts, liver cysts with volume changes during follow-up and patients after fenestration of the cysts should be paid special attention. Regular follow-up and timely monitoring of changes in the patient's condition should be performed. Simultaneously, for patients with atypical imaging findings and complicated liver cysts, the differential diagnosis of intrahepatic cholangiocarcinoma needs to be considered.