Advances in Hepatology

Management of Hepatic Cysts

Jorge L Herrera

G&H What proportion of hepatic cysts require medical attention?

JH The majority of liver cysts (90%) are asymptomatic and are incidental findings in patients who undergo an ultrasound (US) or computed tomography (CT) scan for some unrelated reason. If there are symptoms, they are usually dependent on the size of the cyst. A cyst under 5 cm in diameter is almost never symptomatic, whereas those that are larger may cause symptoms. If there is a cause for concern from a cyst, it is most likely based on the radiologic characteristics uncovered through imaging.

G&H What are the signs, in terms of radiologic presentation, that indicate a cause for concern?

JH First, neoplastic cysts are, for the most part, solitary. When we see multiple cysts that involve several organs, they are almost always benign cysts. When imaging a solitary cyst, the location in the liver does not indicate a greater or lesser risk. More cysts occur in the right lobe, simply because it is larger, but location does not help to differentiate a benign cyst from a neoplastic or potentially malignant cyst.

The test that provides the most useful information is US. Although CT scanning is considered the state of the art in most examinations, US remains the most important test in the imaging of cysts, and CT scans are complementary tests that are utilized in specific cases. US allows us to confirm that the content of the cyst is fluid and anechoic, as well as show the characteristics of the cyst wall. In most simple, non-neoplastic cysts, the wall is smooth and, for the most part, not visible on US, and the interior of the cyst appears clear and without septa or debris. If the US image does show septa, a wall irregularity, or debris, it indicates a raised level of concern that it is a complicated and potentially neoplastic cyst.

US imaging provides all the characteristics and definition of the cyst. A CT scan can locate the cyst within the liver and show how close it is to other structures and the level of viscosity of the fluid. Magnetic resonance imaging (MRI) has virtually no role in the imaging of liver cysts. MRI can be used to differentiate hemorrhaging into the cyst and can distinguish hemorrhage from complex irregularities, but otherwise has no application.

G&H What are the risk factors for the development of hepatic cysts?

JH Hepatic cysts are more common in women than in men, but not by much. There is a 1.5:1 female-to-male ratio. As people get older, the likelihood of occurrence in women versus men increases further.

In research of congenital cysts and polycystic disease, data have shown that the epithelium that lines the cyst and produces fluid is sensitive to hormones, particularly estrogen. Clinical observation has also shown that cysts tend to enlarge more quickly in patients on hormone therapy. Whether this is true in neoplastic cysts is unclear, and these data may have no bearing in the case of neoplastic or malignant cysts. Further, all cysts tend to enlarge over time, at variable rates. Growth of a cyst is not necessarily a sign of neoplastic or malignant features.

Fibrosis and cirrhosis caused by other hepatic diseases, such as viral hepatitis, are not a risk factor for simple cysts or polycystic disease. Congenital hepatic fibrosis is associated with cysts and resembles cirrhosis from viral disease, but, in general, hepatic cirrhosis does not increase the risk of cysts.

G&H Beyond incidental findings, what are the signs or symptoms that might indicate the presence of hepatic cysts?

JH Patients with cysts present as either asymptomatic or with nonspecific, minor symptoms. The differential is completely different if a patient is acutely ill. Patients with a fever or severe pain and single or multiple cystic hepatic lesions on imaging are much more likely to have an amoebic or bacterial abscess rather than a benign or malignant cyst.

In the unusual situation where the patient has a palpable mass in the right upper quadrant, there is a variety of possible causes, one of which is the presence of a cyst.

When cysts are symptomatic, they most commonly cause a dull pain in the right upper quadrant and that will prompt US examination. Rarely, if the cyst is near the main bile ducts, it can cause obstruction and jaundice. If it is large enough to compress the stomach or the small bowel, it can cause early satiety or even vomiting, but these are extremely rare presentations.

G&H Does the presence of cysts ever affect serologic indicators of liver function?

JH In cases of non-neoplastic cysts, in particular, liver tests are usually normal. In cases of congenital polycystic liver disease, where there may be cysts all over the liver, there may be some elevation in the level of alkaline phosphatase, but with isolated cysts, there are no changes in liver tests.

G&H What are the steps in management of a cyst with potentially neoplastic features?

JH It should first be noted that complex cysts, particularly those with neoplastic features, are rare. It is estimated that only about 5% of the general population have any type of hepatic cyst. That is a rough estimate based on autopsy studies, as most cysts are never detected or treated. However, of the cysts that do occur, only about 5% are neoplastic.

If a cyst is less than 1 cm in diameter, details of septation or other irregularities cannot be seen on US imaging. When cysts are that small, they are usually of no clinical importance, and we follow them expectantly. If they grow larger, particularly over 5 cm in diameter, they should be carefully evaluated for any kind of septation, thickened or irregular wall, or internal debris, which suggests the possibility of a biliary cystadenoma or cystadenocarcinoma.

However, a simple cyst that has been infected in the past or has experienced hemorrhage can develop septa. Therefore, the presence of septa does not always denote a neoplastic cyst. Other possibilities include parasitic cysts that can present with septation or an irregular cyst wall, although the patient remains asymptomatic. Tumors in the liver can necrose in the center and form a cystic appearance. There are also rare cases of traumatic cysts that occur in patients who have been in car accidents or had some other violent injury. All of these can look like complex cysts, raising the concern for neoplasia.

G&H What are the next steps, after imaging, in determining whether cysts are neoplastic or malignant?

JH There is some controversy surrounding next steps in the management of a newly identified complex cyst. When a complex cyst is seen on US, the next step would likely be to obtain a CT scan to better localize the lesion and rule out other associated findings that might suggest a malignant process.

Surgical removal and histologic sectioning are the only way to definitively establish whether or not a complex cyst is neoplastic. However, there are other options if the patient cannot undergo surgery.

Before taking any action, a thorough history needs to be taken in order to rule out infection with the Echinococcus parasite, which can cause cyst formation. These parasites are not common in the United States, but they are endemic worldwide and associated with rural areas where sheep are raised. Humans are accidental hosts, not in the normal life cycle of the parasite. However, if the parasite eggs are ingested, the parasite often infects the liver and lungs, and the fluid in the related cysts is infectious. If an infectious cyst is punctured and the fluid leaks into the abdomen, it can cause significant complications, including anaphylaxis. The enzyme-linked immunosorbent assay test for Echinococcus is 90% sensitive and should be performed in patients with a suspected parasitic etiology of their cyst.

For patients where surgery is not an attractive option, once echinococcal disease has been ruled out, the cystic fluid can be aspirated to look for mucin. Mucin in the cystic fluid is highly suggestive of neoplasia. However, a lack of mucin does not rule out a neoplastic cyst. Similarly, the fluid can be checked for the tumor markers carcinoembryonic antigen and Ca 19-9, both of which are associated with neoplastic cysts. Unfortunately, these tests do not have adequate negative predictive value. Therefore, even when normal or negative, malignancy is not excluded. Only a positive mucin or tumor marker screen yields positive predictive information, which is a significant limitation of this manner of screening.

G&H Could you outline the surgical procedure for removal of a complex cyst?

JH The best way to differentiate a complex simple cyst from a neoplastic cyst is to biopsy the cyst wall, which can only be accomplished via surgical procedure. If the cyst is less than 5 cm in diameter, it is less likely to be malignant but it can still be neoplastic. If it is less than 1–2 cm, it should be monitored radiologically, instead of attempting surgery, but if it grows to between 2 cm and 5 cm, and definitely if it is over 5 cm, we must consider surgery, if the cyst has radiologic findings that are suspicious for neoplasia.

Surgical excision of a complicated, potentially neoplastic cyst requires the removal of the entire cyst along with 3–4 mm of surrounding liver tissue on all sides. If the location of the cyst permits, the surgeon may elect to perform a segmental resection of the liver.

Laparoscopy can be utilized in the treatment of symptomatic simple cysts, which can be drained into the peritoneum. In order to remove the entire cyst, open surgery is generally necessary.

Some surgeons may send a sample of the cyst wall for frozen section analysis during the operation to determine whether or not there is any malignancy. If malignancy is detected, the surgeon will most likely do more extensive resection, including the removal of surrounding lymph nodes. However, frozen section analysis is not as accurate as permanent section sampling. Therefore, regardless of frozen section results, a pathologist should examine sections of the complete, removed cysts for any signs of neoplasia or malignancy after the operation.

G&H What is the rate of recurrence after a neoplastic cyst has been removed?

JH If a neoplastic, but not malignant, cyst is removed and the pathology shows successful excision of liver tissue all around it, the rate of recurrence is extremely low. If, for any reason, part of the cyst wall was left behind, the recurrence rate goes up to approximately 50%. Regardless of pathology, all patients should be followed periodically with US. If the cyst showed malignancy but was successfully removed in its entirety, the prognosis for recurrence is still good but there is always the chance of nodal metastasis.