Laboratory Studies
Although liver test results may be normal in patients with biliary cystadenomas, elevation of alkaline phosphatase, bilirubin, and, less commonly, aminotransferase levels can be present.
Superinfection of the tumor may cause leukocytosis with a left shift. Anemia is extremely rare but theoretically possible secondary to bleeding.
Carbohydrate antigen (CA) 19-9 levels may be elevated in some cases. Carcinoembryonic antigen (CEA) and alpha-fetoprotein levels are usually normal.
Cyst fluid analysis at laparoscopy has been proposed in the surgical management of hepatic cysts. Elevated intracystic CA19-9 values were found in biliary cystadenomas compared to those of simple cysts.
Fuks et al found that intracystic fluid concentrations of tumor-associated glycoprotein (TAG) 72 can be used to differentiate hepatic simple cysts from mucinous cysts. Intracystic fluid samples were taken from 118 patients undergoing partial or complete resection of cystic liver lesions, including hepatic simple cysts (75 patients), mucinous cysts (27 patients, including 19 with biliary cystadenomas, four with biliary cystadenocarcinomas, and four with intraductal papillary mucinous neoplasms of the bile duct), and miscellaneous cysts (16 patients). The investigators found that hepatic simple cysts could be differentiated from mucinous cysts—with a sensitivity and specificity of 0.79 and 0.97, respectively—based on a TAG-72 concentration of more than 25 U/mL. [6]
Imaging Studies
Imaging studies are the key element of the workup. On ultrasonography, hepatic cystadenomas appear as anechoic lesions with internal septations. Focal hyperechoic areas within the lesion are common and can represent focal wall fibrosis, intracystic hemorrhage, or papillary projections. [7, 8]
Computed tomography (CT) scanning
On CT scanning, the tumor appears as low-attenuation water density areas with focal enhancement after contrast administration. The septa and the mural nodules often are visualized. Involvement or compression of the portal vein and the biliary tree can be appreciated best by CT scan.
Magnetic resonance imaging (MRI)
MRI can help provide additional information about the nature of the cystic fluid (ie, hemorrhagic vs serous or mucinous). Lesions appear hyperintense on T2-weighted images and hypointense on T1-weighted images, sometimes with reduced perilesional rim signal intensity on T2-weighted images. Intracystic hemorrhage produces higher signal intensity on T1-weighted images than mucinous or bilious fluid content.
Ultrasonography (US)
US is more sensitive in identifying internal septations, whereas CT scan provides anatomical relation to the liver.
A study by Xu et al comparing the imaging features of six intrahepatic biliary cystadenomas with those of seven intrahepatic biliary cystadenocarcinomas indicated that, as seen on conventional US, cystadenomas tend more often to be multilocular than do cystadenocarcinomas, while cystadenocarcinomas are more likely to have a mural or septal nodule and a nodule diameter of over 1 cm. [9]
Other Tests
Endoscopic retrograde cholangiopancreatography (ERCP)
Endoscopic retrograde cholangiopancreatography (ERCP) may demonstrate intraluminal filling defects or a cystic cavity communicating with the biliary tree. Apart from helping in the diagnosis of a cystadenocarcinoma, ERCP is also helpful in decompressing the biliary system in patients with biliary obstruction.
Magnetic resonance cholangiopancreatography (MRCP)
Magnetic resonance cholangiopancreatography (MRCP) is an alternative to ERCP in the evaluation of pancreatic and biliary duct systems. Even though the resolution of MRCP is somewhat inferior to ERCP, the procedure is noninvasive and less expensive.
Procedures
Fine-needle aspiration biopsy
Initial imaging studies should be followed by fine-needle aspiration (FNA) biopsy of the liver, which may help provide important information about the nature of the lesion.
Cytology of the fluid or FNA of prominent papillary projections or wall nodules is useful in helping clarify the diagnosis, even though dissemination of the malignant cells through the needle track is a theoretical concern.
The authors usually choose to proceed with FNA biopsy whenever a question exists regarding the diagnosis of a hepatic tumor. However, remember that needle biopsy findings from hepatic cystadenomas may be misleading because foci of adenocarcinomas can be easily missed.
If the diagnostic suspicion of a hepatic cystadenoma is high, a direct referral for surgical resection is indicated.
Other
A laparoscopic approach with cyst fluid analysis for CA19-9 and CEA followed by cyst wall tissue sampling has been proposed. Elevated CA19-9 levels and premalignant or malignant histology should be followed by radical resection.
Histologic Findings
Solid hepatic lesions may be considered in the differential diagnosis, especially when the lesions appear irregular on imaging studies. Such lesions include FNH, adenomas, angiomyolipomas, and primary hepatic malignancies, such as hepatocellular carcinoma and cholangiocarcinoma.
A histological variant of biliary cystadenoma occurring primarily in women has been described as cystadenoma with mesenchymal stroma. This variant is characterized by the presence of spindle cells in the mesenchymal stroma that are capable of differentiating into different cell types, with a high premalignant potential.
Differentiation of cystadenomas from cystadenocarcinomas is particularly difficult. Imaging studies are not sensitive enough to completely exclude the presence of malignant degeneration in a cystadenoma. Determination of the tumor marker CA19-9 in the serum and in the cyst fluid has been suggested, but CA19-9 also can be expressed in the biliary epithelium lining of benign cystadenomas. For this reason, the presence of CA19-9 is not 100% reliable in the diagnosis of cystadenocarcinoma.
Embryonal sarcoma also is in the differential diagnosis.
Cystadenomas may express a progesterone receptor in the mesenchymal cell component. Other markers demonstrated on immunohistochemistry are CA19-9, CEA, vimentin, and cytokeratin. In situ hybridization has demonstrated selective positivity for albumin messenger RNA in cystadenocarcinomas.
Available evidence shows that biliary cystadenomas tend to occur predominantly in women because these tumors are hormonally responsive. This theory is further supported by immunohistochemical studies demonstrating positive estrogen/progesterone receptors associated with biliary cystadenomas.
