Hepatic Cystadenomas 

Updated: Jun 28, 2021
Author: Krishan Ariyarathna, MD; Chief Editor: BS Anand, MD 

Overview

Background

Hepatic (biliary) cystadenomas are rare multilocular cystic tumors of the liver that are derived from the biliary epithelium and are predominantly located in the right hepatic lobe. These tumors usually involve the hepatic parenchyma (approximately 85% of cases) and occasionally the extrahepatic biliary tract. The size of the tumor is variable and ranges from 1.5-15 cm in diameter; it may weigh as much as 6000 grams.

In 1892, Keen reported the first case of hepatic cystadenoma, which now accounts for 5% of all cystic lesions of the liver.

Hepatic cystadenomas are benign tumors, but they have a high rate of recurrence and a potential for neoplastic transformation in approximately 10% of cases. Removing these tumors and making a proper diagnosis is important, rather than monitoring them as is appropriate for other common benign hepatic tumors, such as focal nodular hyperplasia (FNH), adenoma, and hemangioma.

Pathophysiology

Hepatic cystadenomas appear as multilocular (rarely unilocular) cystic lesions that are surrounded by a smooth and thick fibrous capsule. The tumors contain numerous internal septations and intraluminal papillary projections, which are lined by mucous-secreting cuboidal or columnar biliary epithelium. This epithelium is sometimes surrounded by a dense mesenchymal stroma containing smooth-muscle cells. A loose layer of collagen-containing blood vessels, nerves, and bile ducts further surrounds this area. True connections with the biliary tree are rare.

Traditionally, cystadenomas are thought to originate from the biliary epithelium, possibly from a congenitally aberrant bile duct. Other possibilities are that the tumors arise directly from embryonic foregut cells or peribiliary endocrine cells.

Two types of hepatic cystadenomas are described pathologically, as follows: mucinous and serous. Mucinous cystadenoma is the predominant type (95% of cases) that occurs in women. They are located in the intrahepatic region (84%), the common bile duct (6%), the hepatic ducts (4%), and the gallbladder (2%).

Etiology

The etiology of hepatic cystadenomas is unknown.

The resemblance of embryonic structures, such as the gallbladder and the biliary tree, originating from the foregut suggests that these lesions arise from ectopic remnants. The fact that these tumors have been described as early as the first decade of life supports this theory.

Immunohistochemistry and electron microscopy studies have contradicted the possible origin of these tumors from ectopic ovarian tissue.

Environmental factors may play a significant role. Most tumors appear later in life.

The marked female preponderance suggests a role for hormonal influence.

Epidemiology

United States data

The prevalence of hepatic cystadenomas is low, with fewer than 200 cases reported in the literature. These tumors account for a very small number of all hepatic tumors.

International data

The true prevalence of hepatic cystadenomas in different areas of the world is unknown.

Race-, sex-, and age-related demographics

The true prevalence of hepatic cystadenomas in different races is unknown.

Most tumors (80-85%) occur in women. The etiology of cystadenoma is unclear, but hormonal involvement is possible.

The peak frequency of hepatic cystadenomas is in patients aged 30-50 years (mean age, 41.7-53.4 y), with two thirds of cases occurring in patients aged 40 years or older. These tumors may arise as early as the first or second decade of life; however, they are extremely rare in children.

Prognosis

The prognosis of hepatic cystadenomas is extremely good if patients undergo a complete surgical resection. Improper treatment, such as marsupialization, internal Roux-en-Y drainage, or percutaneous drainage and alcoholization, is associated with almost certain recurrence. In particular, aspiration or partial excision of cystadenomas is associated with a recurrence rate of higher than 90%

Morbidity/mortality

Because of their premalignant potential, untreated lesions carry significant mortality. Some authors report a malignant transformation rate of as high as 20-30%. However, in most series, hepatic cystadenomas carry an extremely low risk of mortality and morbidity after proper surgical resection.[1]

Complications

Complications of hepatic cystadenomas include the following:

 

Presentation

History

Hepatic cystadenomas are often discovered incidentally at a routine physical examination or on imaging studies, such as ultrasound (US) or CT scan. Less frequently, nonspecific symptoms related to the compression of a neighboring organ may be noted. Presenting symptoms depend on the size and the location of the lesion.[2] The final diagnosis is made after surgical resection. Note the following:

  • Roughly 15% of patients present with small intrahepatic lesions, which are usually asymptomatic and discovered incidentally after screening ultrasonography.

  • For larger lesions, the typical presentation is that of an expanding mass in the right upper quadrant accompanied by pain, nausea, vomiting, and, in selected cases, cholangitis and sepsis.

  • Unusual presentations include obstructive jaundice, ascites secondary to portal vein compression, and intracystic hemorrhage. Acute abdomen is a rare presentation and may be caused by the rupture of the cystic wall, intra-peritoneal hemorrhage, or cyst torsion.

Physical Examination

Physical examination findings from patients with hepatic cystadenomas are usually unremarkable unless the tumor has reached a significant size and causes compressive symptoms. Physical examination may reveal a palpable and tender mass in the right upper quadrant or epigastrium and, less commonly, hepatomegaly. Lower-extremity edema and/or signs of portal hypertension may occur in patients with lesions large enough to compress the portal vein or vena cava. Note the following:

  • Splenomegaly may be an indication of a compressive effect on the portal circulation, with the development of portal hypertension. These patients also may develop ascites.

  • Jaundice suggests obstruction of the biliary system. Rare extension of the lesion in a pedunculated fashion inside the biliary system has been described.

  • Obstruction of the inferior vena cava may cause marked lower-extremity edema.

  • In the rare occurrence of intraperitoneal rupture of the lesion, the patient may have signs typical of acute peritonitis.

 

DDx

Diagnostic Considerations

Hepatic cystadenomas are considered in the differential diagnosis of other hepatic cystic lesions, including simple cysts, echinococcal cysts, and cystadenocarcinomas.[3, 4] Intracystic hemorrhage, septations, or mural nodularity can be present both in cystadenomas and in other cystic lesions of the liver. Less commonly, cystadenomas may be confused with necrotic neoplasms, cystic metastases, abscesses, cystic hamartomas, embryonal sarcomas, hematomas, or other congenital cysts. Diagnostic questions also may arise in patients with Caroli disease or other forms of polycystic liver disease. Multiple bile duct hamartomas (von Meyenburg complex) can also mimic biliary cystadenoma, both for presentation and for imaging.[5]

Differential Diagnoses

 

Workup

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.

 

Treatment

Medical Care

No medical treatment has been found to be effective for the management of hepatic cystadenomas.

Discontinuing hormonal treatment until the estrogen/progesterone receptor studies are completed is prudent.

Consultations

Consult with the following specialists for treatment recommendations and procedures in patients with hepatic cystadenomas:

  • Oncologist
  • Hepatobiliary surgeon
  • Interventional radiologist
  • Interventional gastroenterologist

Dietary and activity considerations

No specific diet is recommended. In the presence of biliary obstruction, deficiency of fat-soluble vitamins should be corrected.

Activity is usually not restricted. However, after surgical intervention, standard precautions as in other abdominal surgery should be taken.

Surgical Care

The treatment of choice for hepatic cystadenomas is surgical resection. Complete resection of the tumor is imperative to avoid local recurrence and malignant transformation.[10] Note the following:

  • A complete lobectomy is sometimes necessary for larger lesions or in the presence of adenocarcinoma.

  • For smaller lesions, enucleation alone can usually be accomplished with preservation of the remaining hepatic parenchyma unless the tumor is in a central location close to the hepatic hilum. Enucleation is possible because cystadenomas have a thick fibrous capsule that can be dissected bluntly without major bleeding or biliary leak.

Surgical mortality is not higher than mortality associated with a corresponding hepatic resection or lobectomy.

Liver transplantation may be necessary in the rare occurrence of extensive bilobar extension of the tumor.

In a study of 51 patients, Gamblin et al investigated the efficacy of laparoscopic resection of symptomatic hepatic cysts.[11] According to the histologic examination, 90% of the lesions in the study were simple cysts, and 10% were cystadenomas. All patients who were operated on for pain experienced symptom relief. According to the authors, the study's results support a routine laparoscopic approach to the treatment of benign symptomatic cysts. They concluded that traditional surgical measures should be reserved for cases of expected malignancy or for those in which laparoscopy is contraindicated or the cyst recurs following laparoscopic treatment.

Abu Hilal et al also concluded that the laparoscopic approach represents a safe option for the management of benign and indeterminate liver lesions, even when major hepatectomy is required.[12]

Outpatient follow-up

No further outpatient care is indicated routinely after complete surgical resection. However, because local recurrence of a cystadenoma with progression to cellular atypia and, ultimately, carcinoma has been described, regular postoperative follow-up is indicated. Follow-up is conducted best by performing abdominal US or CT scan at 6-month intervals for the first postoperative year and then annually.[1]