Simple cysts and polycystic liver disease: Clinical and radiographic features and surgical and nonsurgical management

Pathology and pathogenesis

Macroscopically, a simple cyst of the liver has a spherical or ovoid shape. The diameter ranges from a few millimeters to 20 cm or more. The cyst does not communicate with the intrahepatic bile ducts. Small cysts are surrounded by normal hepatic tissue. Large cysts produce atrophy of the adjacent hepatic tissue; a huge cyst may result in complete atrophy of a hepatic lobe, with compensatory hypertrophy of the other lobe. Atrophy respects the large bile ducts and blood vessels, which appear to be abundant in the atrophic tissue in contact with the cyst. Large bile ducts and blood vessels persisting after atrophy may protrude and form folds over the inner surface of the cyst. There is no septation; the cysts are unilocular. The cystic fluid is usually clear; however, intracystic bleeding is relatively common, and the fluid may be brownish when this is the case. Even when a simple cyst is apparently unique, imaging studies disclose the presence of one or more small additional cysts in most patients. In a few cases, simple cysts are multiple, resembling the liver cysts of PCLD, criteria for distinguishing both conditions are given later.

Microscopically, the cysts appear to be bordered by a single layer of cuboidal or columnar epithelial cells, resembling biliary epithelial cells ( Fig. 73.1 ). The cells are uniform, without any atypia. Stroma is absent in small cysts and reduced to a thin layer of connective tissue in large cysts. Simple cysts of the liver are regarded as a congenital malformation. An aberrant bile duct would have lost communication with the biliary tree and would dilate progressively. Liver cyst epithelial cells retain differentiated secretory function; they secrete fluid and generate a positive luminal pressure that may be greater than 30 cm H ₂ O, which accounts for most symptoms. The composition of the fluid, which contains water and mineral electrolytes without bile acids and bilirubin, is close to that of the normal secretion of the epithelium of the bile ducts. It is not toxic for the peritoneum, which is the rationale for cyst fenestration.

Prevalence and etiology

Simple cysts have long been considered rare. By 1971, only 350 cases had been reported, ^, and early estimates from autopsy studies were less than 1%. The development of imaging techniques revealed, however, that simple cysts are much more frequent. Prevalence in US studies is 3% to 5%, ^, was 18% in a more recent spiral computed tomography (CT) study of an adult population, and 24% when using non–contrast-enhanced magnetic resonance imaging (MRI). These discrepancies are explained by the usual small size of most cysts, which are discovered only with accurate imaging techniques. An association between simple hepatic cysts and simple renal cysts has been documented but is unexplained.

The incidence of simple cysts is age and gender related. Simple cysts are uncommon before age 40 years, and their incidence increases sharply thereafter. Simple cysts also are larger in adults older than 50 years than in younger individuals The female-to-male ratio is 1.5:1 for all simple cysts shown at necropsy or imaging. In symptomatic or complicated simple cysts, however, it is 9:1. Huge cysts affect women older than 50 years almost exclusively. Based on these observations, the diagnosis of simple cysts should be retained with caution when a large and/or symptomatic cystic mass is observed in a male patient or in a young woman.

Manifestations and diagnosis

In most cases, simple cysts—all small cysts but also most large cysts—are asymptomatic and fortuitously shown by US or CT (see Chapter 14 ). Only some large cysts produce abdominal pain or discomfort. Because of the high prevalence of simple cysts in adults, the fortuitous coincidence of this lesion and another hepatic or extrahepatic disease is common. The causal relationship between abdominal pain or discomfort and a simple cyst of the liver must be admitted with caution and accepted only if the cyst is large and the other possible causes of the symptoms have been excluded. At clinical examination, only large cysts can be palpated as spherical tumors. In most cases, the fluid content of the tumor can be suspected. In some cases, the cyst is so tense that it may be taken for a solid tumor. The condition of individuals with simple cysts of the liver is good. Liver function tests are normal; abnormal liver function tests in a patient with simple cyst of the liver are not related to the cyst and are caused by another liver disease, except when the cysts compress bile ducts. The cyst fluid contains high concentrations of cancer antigen (CA) 19-9 and carcinoembryonic antigen (CEA) but low concentrations of tumor-associated glycoprotein-72. This may translate to slightly increased serum concentrations of these tumor markers, most notably CA19-9.

US is the best procedure for recognizing simple cysts (see Chapter 14 ). A simple cyst is a circular or oval, totally anechoic lesion, with sharp, smooth borders and strong posterior wall echoes, indicating a well-defined tissue-fluid interface. There is accentuation of the echoes beyond the cyst compared with echoes at a similar depth transmitted through normal adjacent liver tissue (see Fig. 73.1 ). Accentuation of the echoes beyond the cyst, so-called acoustic posterior enhancement , which indicates that the lesion is fluid-filled, is observed only when the deep tissue transmits US and is not seen when a total reflector, such as gas or bone, lies behind the cyst or when the cyst is very posterior. There is neither wall nor septation, but a false image of septation may be seen when two cysts are adjacent. In some patients, intracystic echoes or material can be detected following intracystic bleeding (see later).

The other imaging procedures have less utility in diagnosis compared with US and are generally not required. CT confirms the presence of one or several round or oval, water-dense lesions, without septations or intracystic formations; dynamic CT shows that they are avascular (see Chapter 18 ). In small cysts, recognition of water density may be difficult (the average density of the cyst being obscured by the density of the adjacent liver tissue), and an apparent increase in density may be observed after intravenous (IV) injection of contrast medium. However, CT is not a good imaging method to explore cysts. On MRI, the cyst is homogeneous, very hypointense on T1-weighted images, and very hyperintense (as the gallbladder content) on T2-weighted images ( Fig. 73.2 ). Contrast US shows no enhancement of the cyst wall.

If the patient is living or has been living in an area where hydatid disease is endemic, or if there is any doubt about a possible hydatid cyst, serologic tests for this parasitic infection (although its accuracy is fairly low) as well as MRI should be performed (see Chapters 19 and 74 ).

Course and complications

In most cases, simple cysts are asymptomatic and remain silent; repeated US studies usually show no appreciable changes during years, and surveillance is not required. In some patients, the cysts grow slowly. In a few patients, the size of the cysts increases rapidly; such a course, which may be associated with severe pain and discomfort, is observed almost exclusively in women older than 50 years.

Complications are uncommon. Intracystic bleeding is the most frequent. ^, It is presumed to result from the erosion of an artery adjacent to the cyst. The clinical manifestations consist of sudden, severe pain and increase in the size of the cyst. The pain resolves in a few days. In a few cases, pain is mild or absent. There is no evidence of anemia, and the biologic liver tests show only a moderate elevation of γ-glutamyltransferase.

On US, echoic material, corresponding to clots, is present within the cyst ( Fig. 73.3 ); usually this echoic material is mobile, sliding in the inferior part of the cyst (see Chapter 14 ). Hemorrhagic cysts also become hyperintense on T1-weighted MRI, whereas uncomplicated cysts are hypointense (see Fig. 73.2 ; see also Chapter 14 ). After gadolinium injection, there is frequently an enhancement of the periphery of the cyst when hemorrhage is recent, which corresponds to compressed liver parenchyma ( Fig. 73.4 ). Communication with the bile duct lumen, presumably also by an erosive mechanism, may develop. Bacterial infection is, in contrast, exceptional. It seems to be more frequent in the presence of renal insufficiency, dialysis, and, above all, in polycystic liver. In that case, a positron emission tomography (PET)–CT can be useful to localize the infected cyst among other cysts. In general, a giant infected cyst can be diagnosed with CT scan. In case of infected giant cyst, medical treatment is insufficient, and prolonged drainage or a surgical approach is necessary.

Spontaneous rupture into the peritoneal cavity ( Fig. 73.5 ) ^, or, more rarely, the pleural cavity or the duodenum is exceptionally rare. In contrast to hydatid cysts, peritoneal perforation of simple cysts is self-limited. Severe hemoperitoneum has been described only in patients receiving anticoagulation ^, with very few exceptions.

There are also anecdotal case reports of traumatic rupture of simple cysts mimicking an acute surgical abdomen.

Because simple cysts are tense, they may compress the bile ducts or the inferior vena cava (IVC; Fig. 73.6 ), and although anecdotal, pulmonary embolism after clot formation has been reported. Acute Budd-Chiari syndrome (see Chapter 86 ) has also been reported. As will be discussed later in this chapter, with these conditions, compression of biliary branches or hepatic veins is a potential source of intraoperative or postoperative complications.

Differential diagnosis

Hydatid cysts, liver abscesses, and cystadenomas and cystadenocarcinomas are the main differential diagnosis (especially when simple cysts have become atypical). They are addressed in Chapters 72 , 70 , and 88B , respectively.

Embryonal sarcomas are mostly observed in children between the ages of 2 and 15 years and are exceptional in adults. The tumor is usually large and poorly differentiated with abundant myxoid or necrotic content. Although the tumor may appear as cystic on CT and MRI, because of the very high water content of the myxoid stroma, US shows that it is, in fact, solid. Late-phase imaging after contrast injection during CT and MRI shows late enhancement, which is incompatible with a cystic tumor.

Other primary tumors, including hepatocellular carcinoma and cholangiocarcinoma, may occasionally be cystic. The cystic appearance corresponds to necrosis that may be either spontaneous (in particular for rapidly growing tumors) or treatment induced. However, with few exceptions, these tumors remain mostly solid. Giant hemangiomas may occasionally present as partly cystic. This corresponds to noncirculating areas. Hemangiomas are hypointense on T1-weighted images and hyperintense on T2-weighted images (as any cystic lesion), but the kinetics of contrast enhancement is typical (see Chapter 19 ).

Intrahepatic pseudocysts in the context of acute pancreatitis or pancreatic ducts rupture are exceptional, with less than 20 reported cases (see Chapter 55 ). They may be located in the left side of the liver (along the lesser omentum) or the right side of the liver (along the right portal vein). They have a subcapsular location, a hemorrhagic or necrotic content, and a fibrous wall that enhances at the late phase of the injection. Magnetic resonance cholangiopancreatography (MRCP) is useful to (occasionally) document rupture of the pancreatic duct (see Chapter 17 ). Liver hematomas are rarely spontaneous and usually appear in the context of trauma or liver surgery. They have also been described in association with hepatocellular carcinoma, liver adenoma or, very rarely, metastases. When occurring at the end of a pregnancy, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome should be suspected. Clinical symptoms are usually obvious with pain and sometimes hypotension. When the clots are fresh, these hematomas are spontaneously echogenic on US, hyperdense on CT scan, hyperintense on T1-weighted, and hypointense on T2-weighted MRI sequences. At a later phase, clots liquefy, and the content appears cystic.

Bilomas are cystic lesions containing bile as a result of spontaneous, traumatic, or iatrogenic bile duct rupture. These may be surrounded by a fibrous capsule. Biliary anomalies (dilation, stenosis, or a combination of these) are frequent.

Ciliated hepatic foregut cysts

Ciliated hepatic cysts have been described in all areas where the foregut extends during the embryonic period, including the sublingual area, esophagus, stomach, ileum, pancreas, and gallbladder. They also may be present within the liver. Although extremely rare, ciliated hepatic cysts warrant special consideration.

When located within the liver, ciliated cysts are located within the liver parenchyma and have a characteristic four-layer border that consists of a pseudostratified ciliated columnar epithelium covering a subepithelial connective tissue, smooth muscle bundles, and an outer fibrous capsule. The lining epithelium may secrete fluid of different composition (from nearly water to viscous or mucous), which explains why its echogenicity may be variable and why calcifications may be present, although exceptionally. The second characteristic of these cysts is that they are subcapsular, usually located on the anterior surface of the liver close to the insertion of the falciform ligament. Two-thirds are localized in the left lobe of the liver in segment IV, but right lobe cysts also have been described. ^, The final characteristic of these cysts is that they are classically unilocular and usually less than 4 cm in diameter. Typically, these cysts do not communicate with the biliary system, although this has been reported, particularly in children.

Ciliated hepatic cysts, although known since 1857, are rare, with approximately 100 cases reported in the literature, most in the past 20 years. There is no gender predominance, and the age of the patients ranges from newborn with prenatal diagnosis to 82 years (mean age, 48 years).

Most ciliated hepatic foregut cysts are asymptomatic (two-thirds of reported patients) and discovered incidentally during abdominal imaging studies or surgical explorations. Abdominal symptoms are rare, probably because of their small size. When present, the most frequent symptom is epigastric or right upper quadrant abdominal pain that can be observed even with small cysts because of their subcapsular location.

The three characteristics on imaging are their predominant location in segment IV, their small size (4 cm ± 2 cm), and their subcapsular location. Most (>90%) are unilocular. Two-thirds of the cysts are hypoechoic on US, are hypodense on CT, and do not enhance after injection of contrast material ( Fig. 73.7 ). They are anechoic as formal biliary cysts in less than 5%. Some ciliated cysts also may have an atypical solid tumor appearance on CT and a noncystic appearance on US (hyperechoic), probably as a result of mucinous material, calcium, and cholesterol crystals within the cyst. On MRI, the lesion is highly hyperintense on T2-weighted images but highly variable on T1 sequences, being hyperintense in 52%, isointense in 24%, and hypointense in 14%. When atypical on imaging, the differential diagnosis includes cystadenoma or cystadenocarcinoma (see Chapter 88B ) and may be difficult, especially because CA19-9 may be expressed by the epithelium of the ciliated cysts, and its serum level may be slightly elevated. Fine-needle aspiration cytology may be helpful by showing ciliated pseudostratified tall columnar epithelial cells suspended in a mucous background. The presence of these cells is virtually diagnostic of this condition, and the positive predictive value of aspiration is 76%.

Ciliated hepatic foregut cysts are usually thought to follow a benign course. Compression of adjacent structures is extremely rare, with a single case report of portal compression resulting in portal hypertension and another in jaundice. Malignant transformation into squamous cell carcinoma has been reported in four patients in recent years, whereas one other patient had extensive squamous metaplasia, yielding a risk of malignancy of less than 5%. Because this transformation has occurred in patients with cysts larger than 7 cm, most authors agree that excision is indicated when the cyst is larger than 4 to 5 cm, enlarges, shows abnormalities in its wall, or is symptomatic, although other authors have broader indications.

Management

Asymptomatic liver cysts, even when large, need no treatment and do not require surveillance. A small percentage of patients have symptoms related to an increase in the size of cysts, which is often correlated with an intracystic hemorrhage or a cystic infection. Caution must be exercised when considering whether a simple cyst is symptomatic when it is smaller than 8 cm or when it does not protrude outside of the liver surface without a compression of a close organ. If this is not the case, or if symptoms are vague, US-guided aspiration of the cyst may be attempted as a therapeutic test. If this does not result in improvement of symptoms, further treatment is not required. When aspiration is effective at relieving symptoms, the cyst is symptomatic. Improvement, however, is transient, because the cyst inevitably recurs after simple aspiration, and more effective and durable treatment should be considered.

It is unclear whether treatment is indicated in patients who are asymptomatic but have evidence on imaging of compression of the bile ducts, the vena cava, or of portal or hepatic veins by the cysts. When a patient is completely asymptomatic and there is no vascular or parenchymal consequence of the compression of the vena cava or the hepatic vein, no treatment is required. Treatment can be considered when there is a compression of the hepatic vein and vascular abnormalities in the noncystic liver parenchyma, or if there is ascites, reflecting a “suffering” noncystic liver parenchyma, even if the patient is asymptomatic. However, if these anomalies are unilateral (i.e., at least one hemiliver has normal biliary drainage and normal inflow and outflow), our opinion is that treatment is not required because the stenosis is not always reversible ( Fig. 73.8 ).

Treatment of symptomatic cysts relies on the destruction of the epithelial lining (sclerotherapy) or on the creation of a communication between the cyst and the peritoneal cavity (unroofing, also known as fenestration). Sclerotherapy is performed under US guidance, whereas unroofing is currently mostly performed by laparoscopy. Hence symptomatic patients today are most likely to undergo a minimally invasive procedure. This should not lead to an extension of the indications because complications, occasionally severe ones, may occur. It is also important to warn patients early on that these treatments aim at transforming a large, symptomatic cyst into a small, asymptomatic one, and that they should not worry if some anomalies persist on imaging after the procedure.

Sclerotherapy

Complications

Although the injection is painful (which is why the procedure is performed under general anesthesia), pain resolves rapidly, and most patients are discharged the next day. Transient neuropsychic disorders secondary to diffusion of alcohol through the cyst wall have been reported. Intracystic bleeding or cystic infection is rare but potentially severe ( Fig. 73.9 ). It should be realized that vessels are compressed at the periphery of enlarged cysts because of the high intracystic pressure and are therefore not visible; however, bleeding may occur once the cysts have emptied if a vessel has been inadvertently punctured.

Inflammatory changes are frequent after sclerotherapy and may interfere with imaging follow-up. They may also increase the difficulty of subsequent fenestration if sclerotherapy has been ineffective.

Long-term outcome

An initial systematic literature review published in 2001 identified 112 patients treated by alcohol sclerotherapy and 17 treated with minocycline hydrochloride instillation. In most patients, a complete or partial regression of the cyst was seen, but follow-up was short overall. Although the technique has developed, the reported experience since then has been limited. A recent systematic review on 16 studies involving 526 patients showed a 90% to 100% volume reduction in studies with a follow-up of 12 months or more and disappearance of symptoms in 79% to 100% of patients in series published over the past 20 years. Hemorrhagic cysts with hemorrhagic aspirate can be associated with a lower reduction of the volume of the cyst at 1 month, which can be a risk factor of incomplete clinical response.

An early morphologic assessment, usually by US, is frequently performed. However, patients should be warned that this is likely to show the persistence of the cyst, although at a smaller size; this is not predictive of symptomatic recurrence. Moreover, the cyst volume reduction is not the best reflection of the success of the aspiration sclerotherapy procedure; instead, the assessment of the symptoms is the best predictive factor of the success of this treatment. In practice, several months—perhaps up to a year—may be required to achieve optimal efficacy after alcohol sclerotherapy ( Fig. 73.10 ).

Fenestration

Limitations

Cysts protruding into segments VII or VIII are not formal contraindications to laparoscopic fenestration, but the procedure is unlikely to be very successful in such a case because limited access will prevent wide unroofing. In addition, the margins of the opening may adhere to the diaphragm, and the risk of postoperative cyst recurrence is increased as a result of contained secretion. There is also a risk of intraoperative injury to the diaphragm ( Fig. 73.11 ). Open fenestration is a wise alternative in this circumstance.

Sclerotherapy versus fenestration

Although both techniques have been used for years, no randomized or prospective comparative analysis has been done. As a rule, the severity of symptoms that leads to treatment has not been standardized, and recurrence is poorly defined. It would seem that both methods are almost as effective. ^{, ,} Our policy is to systematically attempt sclerotherapy first, whatever the size of the cyst; fenestration is indicated in cases of recurrence, but location of the protruding part of the cyst may influence this choice, or when the patient wants to be relieved of the pain immediately (see Fig. 73.11 ).

Genetics