Biliary cysts

INTRODUCTION — Biliary cysts, also termed choledochal malformations, are cystic dilations that may occur singly or in multiples throughout the biliary tree. They were originally termed choledochal cysts due to their involvement of the extrahepatic bile duct. However, the original clinical classification [1] was revised in 1977 to include intrahepatic cysts [2]. Biliary cysts are associated with significant complications such as ductal strictures, stone formation, cholangitis, pancreatitis, rupture, and secondary biliary cirrhosis. In addition, some types of biliary cysts have a high risk of malignancy.

This topic will review the pathogenesis, clinical manifestations, diagnosis, and management of biliary cysts. Cholangiocarcinoma, gallbladder cancer, and a detailed discussion of type V biliary cysts (Caroli disease) are found elsewhere. (See "Epidemiology, risk factors, anatomy, and pathology of cholangiocarcinoma" and "Pathology of malignant liver tumors" and "Clinical manifestations and diagnosis of cholangiocarcinoma" and "Adjuvant and neoadjuvant therapy for localized cholangiocarcinoma" and "Gallbladder cancer: Epidemiology, risk factors, clinical features, and diagnosis" and "Caroli disease".)

TYPES OF BILIARY CYSTS — The most widely accepted classification scheme for cysts of the extrahepatic bile ducts (choledochal cysts) was proposed initially in 1959 [1]. It was expanded in 1977 to include intrahepatic cysts [2] and further refined in 2003 to incorporate the presence of an abnormal pancreaticobiliary junction (APBJ) [3]. (See 'Abnormal pancreatobiliary junction' below.)

The classification scheme defines six types of biliary cyst (figure 1) [3-5]:

●Type I cysts (50 to 85 percent of cysts) – Type I cysts are characterized by cystic or fusiform dilation of the common bile duct (image 1) [2,6]. Type I cysts do not involve the intrahepatic bile ducts. Type I cysts are further subcategorized as [3]:

•Type IA – Cystic dilation of the common bile duct, as well as part or all of the common hepatic duct and extrahepatic portions of the left and right hepatic ducts. Type IA cysts are associated with an APBJ. The cystic duct and gallbladder arise from the dilated common duct.

•Type IB – Focal, segmental dilation of an extrahepatic bile duct (often the distal common bile duct). Type IB cysts are not associated with an APBJ.

•Type IC – Smooth, fusiform (as opposed to cystic) dilation of all the extrahepatic bile ducts. Typically, the dilation extends from the pancreatobiliary junction to the extrahepatic portions of the left and right hepatic ducts. Type IC cysts are associated with an APBJ.

•Type ID – Cystic dilation of the common duct and cystic duct.

●Type II cysts (2 percent of cysts) – Type II cysts are true diverticula of the extrahepatic bile ducts. They may arise from any portion of the extrahepatic bile duct.  

Studies have highlighted the occurrence of small peri-ampullary bile duct diverticula, which (in contrast to true type II cysts) are not associated with an APBJ, occur in older individuals, and have not been associated with an increased risk of malignancy [7,8]. These presumably acquired diverticula may be associated with elevated sphincter of Oddi pressures or presence of a duodenal diverticulum.  

●Type III cysts (1 to 5 percent of cysts) – Type III cysts are cystic dilations limited to the intraduodenal portion of the distal common bile duct and are also known as choledochoceles (figure 2). Type III cysts can be lined by duodenal or biliary epithelium and may arise embryologically as duodenal duplications involving the ampulla. As many as five subtypes have been described [9]; however, most commonly they are subdivided into two types [10-13]:

•Type IIIA – The bile duct and pancreatic duct enter the cyst, which then drains into the duodenum at a separate orifice. Type IIIA cysts typically present as cystic bulges of the intra-ampullary common bile duct.

•Type IIIB – A diverticulum of the intraduodenal common bile duct or intra-ampullary common ductal channel. These typically present as a pendulous fluid-filled mass within the duodenal lumen, distal to and arising from the major papilla.

●Type IV cysts (15 to 35 percent of cysts) – Type IV cysts are defined by the presence of multiple cysts and are subdivided based on their intrahepatic bile duct involvement:

•Type IVA – Both intrahepatic and extrahepatic cystic dilations. Type IVA is the second most common type of biliary cyst and is often associated with a distinct change in duct caliber and/or a stricture at the hilum, features that help differentiate it from a type IC cyst [3].

•Type IVB – Multiple extrahepatic cysts but no intrahepatic cysts.

●Type V cysts (20 percent of cysts) – Type V cysts are characterized by one or more cystic dilations of the intrahepatic ducts, without extrahepatic duct disease. The presence of multiple saccular or cystic dilations of the intrahepatic ducts is known as Caroli disease and is part of the spectrum of autosomal recessive polycystic kidney disease. (See "Caroli disease".)

●Type VI cysts (rare) – Isolated cystic dilatations of the cystic duct.

EPIDEMIOLOGY — The incidence of biliary cysts in Western populations has been estimated to be 1:100,000 to 1:150,000 [6]. The incidence is higher in some Asian countries (up to 1:1000) [14], with between one-half and two-thirds of the reported cases occurring in Japan [6,14]. A report from Finland suggests that the incidence of biliary cysts has increased from 1:128,000 to 1:38,000 over the past 40 years [15]. Biliary cysts are more common in females, with a female to male ratio of 3:1 to 4:1 [2,5,14]. The majority of cases have been reported in children, although some modern series report equal numbers in adults and children [16].

PATHOGENESIS — Several theories of biliary cyst formation have been proposed, and it is likely that no one mechanism accounts for all biliary cysts [5]. In many patients, an abnormal pancreatobiliary junction appears to play an important role. (See 'Abnormal pancreatobiliary junction' below.)

Cysts may be congenital [17] or acquired [18] and have been associated with a variety of anatomic abnormalities. A genetic or environmental predisposition to biliary cysts is suggested by reports of the familial occurrence of cysts [19] and by the increased incidence in some Asian countries.

Associated conditions — Developmental anomalies associated with biliary cysts include:

●Abnormal pancreatobiliary junction

●Biliary atresia

●Double common bile duct

●Duodenal atresia

●ACTG2-associated visceral myopathy

●Colonic atresia

●Imperforate anus

●Pancreatic arteriovenous malformation

●Multiseptate gallbladder

●Hemifacial microsomia with extracraniofacial anomalies (OMENS plus syndrome)

●Ventricular septal defect

●Aortic hypoplasia

●Congenital absence of the portal vein

●Heterotopic pancreatic tissue

●Familial adenomatous polyposis

●Autosomal recessive and autosomal dominant polycystic kidney disease

Congenital cysts — Congenital cysts may result from an unequal proliferation of embryologic biliary epithelial cells before bile duct cannulation is complete [20,21]. Fetal viral infection may also have a role, as reovirus ribonucleic acid (RNA) has been isolated from biliary tissue of neonates with infantile biliary obstruction and biliary cysts [22]. In addition, cyst formation may be the result of ductal obstruction or distension during the prenatal or neonatal period. In a sheep model, bile duct ligation in neonates led to cyst formation, whereas duct ligation in adult animals led to gallbladder distension [23].

Abnormal pancreatobiliary junction — Some biliary cysts may be the result of an abnormal pancreaticobiliary junction (APBJ), also called pancreaticobiliary maljunction or malunion. The APBJ may allow reflux of pancreatic juice into the biliary tree with resultant damage to the biliary epithelium and cyst formation.

While APBJ is a rare congenital anomaly, with a prevalence of 0.03 percent in one population-based series from Japan [24], it is present in 50 to 80 percent of patients with biliary cysts (image 2 and image 3 and image 1) [25,26]. An APBJ may also be a significant risk factor for the development of malignancy within a biliary cyst [27] or the gallbladder [28]. (See 'Abnormal pancreatobiliary junction and cancer' below.)

APBJ is characterized by a junction of the bile duct and pancreatic duct outside the duodenal wall with a long common ductal channel leading to the duodenal lumen (at least 8 mm, and often over 20 mm, in length) [28-30]. APBJ may result from failure of the embryological ducts to migrate fully into the duodenum. In support of this hypothesis is the observation that the ampulla of Vater is diminutive or flat in patients with APBJ. In one series, the papilla was displaced distally in the duodenum of patients with APBJ, with the distal displacement of the papilla corresponding to the length of the common channel [30].

A long common channel may predispose to reflux of pancreatic juice into the biliary tree since the ductal junction lies outside of the duodenal wall and the sphincter of Oddi [31]. This can result in increased amylase levels in bile [32], intraductal activation of proteolytic enzymes, and alterations in bile composition. A bile amylase concentration of >8,000 International Units/L may be considered diagnostic of an APBJ [26]. These changes could theoretically lead to biliary epithelial damage with inflammation, ductal distension, and eventually, cyst formation. Elevated sphincter of Oddi pressures have been documented in APBJ and could promote pancreaticobiliary reflux [33,34].

Acquired cysts — Rarely type 1 biliary cysts can occur after cholecystectomy [35]. In one series that included 27 patients, six had an APBJ, and 21 had elevated bile amylase levels diagnostic of pancreaticobiliary reflux. Sphincter of Oddi stenosis might contribute to cyst formation in these patients. The risk of biliary malignancy in such patients is unknown.

HISTOLOGY — Histologic features of biliary cysts are variable, ranging from normal bile duct mucosa to carcinoma [6,36]. More commonly in children, there is a densely fibrotic cyst wall with evidence of chronic and acute inflammation [6]. In adults, there are frequently inflammatory changes, erosions, sparse distribution of mucin glands, and not infrequently, metaplasia and biliary intraepithelial neoplasia (BilIN), precursors of cholangiocarcinoma [6,37,38]. Malignancy, when present, is most commonly found in the posterior cyst wall [36]. In the case of type III cysts, the cyst is usually lined by duodenal mucosa and less commonly by bile duct epithelium [10]. (See 'Types of biliary cysts' above.)

CLINICAL MANIFESTATIONS

Presentation — The majority of patients with biliary cysts will present before the age of 10 years [39]. The classic presentation includes the triad of abdominal pain, jaundice, and a palpable mass, and is more common in children than adults [40]. However, most patients will only have one or two elements of the triad [6,41]. Patients may also report nausea, vomiting, fever, pruritus, and weight loss. Infants typically present with obstructive jaundice and abdominal masses, children more often present with abdominal pain and nausea/vomiting, and adults frequently present with pain, fever, nausea/vomiting, and jaundice [39,42]. Biliary cysts may also be an incidental finding during prenatal ultrasonography or in an asymptomatic patient who is undergoing imaging or endoscopic retrograde cholangiopancreatography (ERCP) for other reasons.

Patients may also present with signs and symptoms related to complications associated with biliary cysts, including malignancy, pancreatitis, cholangitis, and obstructive jaundice. (See 'Complications other than cancer' below.)

Laboratory tests — Serum liver tests are often normal in patients with biliary cysts. This reflects absence of biliary obstruction. In the presence of an obstructing stone, stricture, or malignancy, serum liver tests will typically be elevated in a cholestatic pattern (disproportionate elevations of the alkaline phosphatase, gamma-glutamyl transpeptidase, and bilirubin relative to the aminotransferases) (see "Approach to the patient with abnormal liver biochemical and function tests"). However, patients with acute bile duct obstruction by a stone may initially present with marked elevations of serum aminotransaminases. Laboratory evidence of complications may also be present (eg, elevated pancreatic enzymes with pancreatitis, elevated white blood cell count with cholangitis). (See 'Complications other than cancer' below.)

Cancer risk — Biliary cysts are associated with an increased risk of cancer, particularly cholangiocarcinoma [43] but also pancreatic and gallbladder cancers. Cancer is more common in patients who are older and in those with type I and IV cysts. Because of the increased risk of malignancy, it is recommended that patients with type I or IV cysts have the cysts completely removed with Roux-en-Y hepaticojejunostomy. The risk of cancer appears to be lower in patients with type II or III cysts. Patients with type II cysts can often be treated with simple cyst excision, while those with type III cysts can be treated with sphincterotomy or endoscopic resection [13]. Patients with type V cysts have a moderate risk of cancer, but because of the intrahepatic nature of the cysts, treatment can be difficult and some patients require liver transplantation. (See 'Management' below and "Caroli disease", section on 'Management'.)

Overall, the incidence of cancer is reported to be in the range of 10 to 30 percent with a mean age at diagnosis of 32 years [43-45]. However, the cited statistics may overestimate the risk of cancer in biliary cysts because most series include only symptomatic patients presenting with complications, including malignancy. To calculate the true risk of malignant degeneration, the incidence of asymptomatic biliary cysts in the population should be used as the denominator, a value that is unknown. If patients who developed malignancy at least two years after initial diagnosis of their cyst are studied, the incidence appears lower (4.5 percent rather than 14 percent in one series) [37].

Nevertheless, evidence clearly points to a 20- to 30-fold increased risk of cholangiocarcinoma in biliary cysts compared with the general population [43]. This evidence includes the occurrence of cholangiocarcinoma in patients as young as 10 years of age [46], the occurrence of synchronous and metachronous biliary cancers, and the subsequent development of cancer in patients with incompletely resected cysts [47,48]. The possibility of cancer should always be considered in an adult with a newly diagnosed biliary cyst.

Age — The incidence of malignancy increases with age. In two reviews of all published series of biliary cysts, the incidence of cancer was 0.4 percent in patients under 18 years of age, and 11 percent in all adults. Among adults, the incidence increased with each decade of life from 5 percent in patients 18 to 30 years of age to 38 percent in patients over 60 years of age [49]. Some studies have reported a cancer incidence as high as 50 percent in older patients [46].

Cyst type — Cancer has been associated with all subtypes of biliary cysts, but is probably most common in type I and type IV cysts. In one series, 68 percent of the malignancies occurred in patients with type I cysts, and 21 percent occurred in patients with type IV cysts [50]. Cancer has been reported in up to 10 percent of adults with type III cysts [51], and those whose cyst is lined by biliary, rather than duodenal, epithelium may be at higher risk [52]. Type V cysts (Caroli disease) have also been associated with a 7 to 15 percent risk of malignancy [5,43,53]. Multiple studies have described molecular changes that occur during the evolution to malignancy, but their role in diagnosis or management is unclear [43].

Abnormal pancreatobiliary junction and cancer — The presence of an abnormal pancreatobiliary junction (APBJ) increases the risk of malignancy. In one Asian study, the increased incidence of cholangiocarcinoma in biliary cysts was confined to patients with an APBJ, [27] and in a large European series, cancer occurred in cysts with or without an associated APBJ but was more likely when an APBJ was present [26]. In addition, APBJ appears to increase the risk of biliary and pancreatic malignancy in patients without a biliary cyst or ductal dilation [54-57]. K-ras mutations and p53 overexpression have been demonstrated in the biliary mucosa of such patients [58]. Gallbladder cancer is the most common malignancy seen in patients with APBJ who do not have a biliary cyst, and prophylactic cholecystectomy in patients with APBJ has been advised [56]. Surveillance of the bile duct may be warranted after cholecystectomy [59]. (See "Gallbladder cancer: Epidemiology, risk factors, clinical features, and diagnosis", section on 'Abnormal pancreaticobiliary duct junction'.)

Complications other than cancer — Nonmalignant complications of biliary cysts include [6,25,39,41]:

●Cystolithiasis (stone and sludge formation in the cyst)

●Cholelithiasis

●Choledocholithiasis

●Hepatolithiasis

●Cholangitis

●Acute and chronic pancreatitis

●Intraperitoneal cyst rupture

●Secondary biliary cirrhosis due to prolonged biliary obstruction and recurrent cholangitis

●Bleeding due to erosion of the cyst into adjacent vessels or as the result of portal hypertension, often presenting as gastrointestinal hemorrhage due to hemobilia  

●Gastric outlet obstruction due to obstruction of the duodenal lumen

●Gallbladder volvulus

●Intussusception

Stones and pancreatitis are more commonly encountered in patients with type III cysts.

DIAGNOSIS — A biliary cyst should be considered when a dilated portion of the bile ducts or ampulla is identified on imaging, especially in the absence of biochemical, radiographic, or endoscopic evidence of obstruction. A high level of suspicion is required for diagnosis, particularly for type I cysts, which may go undiagnosed unless considered in the differential diagnosis of patients found to have ductal dilation. The diagnosis can typically be made with a combination of transabdominal ultrasonography and cross-sectional imaging with computed tomography (CT), taking the clinical context into account. Additional testing may be required to rule out biliary obstruction (magnetic resonance imaging [MRI] with magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or endoscopic ultrasound [EUS]), to confirm communication of the cyst with the biliary tree (hepatobiliary scintigraphy or ERCP), or to diagnose the presence of an APBJ (ERCP) [60].

Diagnostic approach — It is important to consider the diagnosis of a biliary cyst in a patient found to have a dilated bile duct or cystic liver lesion(s). Patients suspected of having biliary cysts should undergo an evaluation to confirm the presence of the cysts and to determine whether there is communication between the cysts and the biliary tree. In children and adults, cysts are often first suspected based on the findings from transabdominal ultrasonography or CT in a patient being evaluated for abdominal pain, jaundice, or an abdominal mass. With the widespread use of CT and MRI, many cysts are discovered incidentally during abdominal imaging performed for an unrelated reason, and an increasing proportion of biliary cysts are incidentally detected in utero during prenatal ultrasound exams. (See 'Clinical manifestations' above and "Diagnostic approach to the adult with jaundice or asymptomatic hyperbilirubinemia", section on 'Evaluation' and "Diagnosis and management of cystic lesions of the liver".)

If a biliary cyst is suspected in a child or adult based on an ultrasound, cross-sectional imaging with CT or MRI with MRCP is typically the next step in diagnosis. Cross-sectional imaging can confirm the presence of a cyst, determine if the cyst communicates with the biliary tree, and evaluate for an associated mass. MRI/MRCP is often preferred because it does not use ionizing radiation, may demonstrate an APBJ, and can assess for an obstructing lesion within the biliary tree or pancreas (see 'Transabdominal ultrasound' below and 'Computed tomography' below and 'Magnetic resonance cholangiopancreatography' below). Children who are incidentally found to have a dilated bile duct on ultrasound, without typical findings of a biliary cyst or APBJ on subsequent imaging, can probably be followed conservatively, with biliary dilatation resolving in 40 percent [61].

Following cross-sectional imaging, some patients will require additional testing:

●Types I and IVA cysts – If concern remains for an obstruction following MRCP (eg, because the liver tests are elevated in a cholestatic pattern), an ERCP and/or EUS should be performed. These tests provide direct visualization of the ampulla as well as the peri-ampullary bile duct and pancreatic duct and can evaluate for evidence of obstruction at either the proximal or distal end of the cyst and evidence of malignancy. (See 'ERCP and other forms of direct cholangiography' below and 'Endoscopic ultrasound' below.)

●Types II and IVB cysts – If it is unclear whether the cyst communicates with the biliary tree after cross-sectional imaging, confirmation may be obtained by hepatobiliary scintigraphy, ERCP, or EUS. EUS may be particularly helpful for distinguishing a pancreatic head cyst or pseudocyst from a type II biliary cyst [62]. (See 'Hepatobiliary scintigraphy' below and 'ERCP and other forms of direct cholangiography' below.)

●Type III cysts – ERCP can confirm the presence of a type III cyst and permits endoscopic therapy and cyst mucosal biopsy during the same examination. (See 'Type III cysts' below.)

●Type V cysts – Typically, the diagnosis is established when imaging studies demonstrate intrahepatic bile duct ectasia and multiple irregular cystic dilations of the large proximal intrahepatic bile ducts with a normal common bile duct. If needed, biliary scintigraphy can confirm that the cystic dilations communicate with the biliary tree. Rarely, liver biopsy is needed to confirm the diagnosis. (See "Caroli disease", section on 'Diagnosis'.)

Percutaneous or intraoperative cholangiography (alternatives to ERCP) can also be performed to examine the biliary tree. (See "Percutaneous transhepatic cholangiography in adults".)

Studies have described a sequence of epigenetic changes in biliary dysplasia and carcinoma, raising the possibility that assays of blood or bile for methylated DNA markers might detect early malignancy in patients with biliary cysts [63]. However, appropriately validated clinical-grade assays are not available.

Biliary mucinous cystic neoplasms (biliary cystadenomas and cystadenocarcinomas) typically present as solitary cystic lesions of the liver and are discussed elsewhere. (See "Diagnosis and management of cystic lesions of the liver".)

Imaging test characteristics — Multiple imaging modalities are available to evaluate biliary cysts, including transabdominal ultrasound, CT, MRCP, ERCP, EUS, and hepatobiliary scintigraphy. Biliary cysts may be diagnosed prenatally by fetal ultrasound or MR. Which test(s) to obtain will depend on the patient's presentation and prior testing. (See 'Diagnostic approach' above.)

Transabdominal ultrasound — Transabdominal ultrasound has a sensitivity of 71 to 97 percent for diagnosing biliary cysts [64]. Factors that may limit the usefulness of an ultrasound include the patient's body habitus, the presence of bowel gas, and limited visualization due to overlying structures. Ultrasound frequently misses type III cysts [65].

Communication with the biliary tree must be demonstrated in order to differentiate biliary cysts from other cystic lesions (eg, typical simple liver cysts). While ultrasound may show communication with the bile duct [66], the findings are typically confirmed with other imaging modalities (eg, CT, MRCP, ERCP, or scintigraphy).

Computed tomography — CT can detect all types of biliary cysts. It can demonstrate continuity of the cyst with the biliary tree, examine the relationship of the cyst to surrounding structures, and evaluate for the presence of malignancy. It is also useful for determining the extent of intrahepatic disease in patients with type IVA or V cysts.

Computed tomographic cholangiography has been used to delineate the anatomy of the biliary tree and has high sensitivities for visualizing the biliary tree (93 percent), diagnosing biliary cysts (90 percent), and diagnosing intraductal stones (93 percent) [67]. However, its sensitivity is lower for imaging the pancreatic duct (64 percent), and its sensitivity for diagnosis of abnormal pancreatobiliary junction is poor.

Magnetic resonance cholangiopancreatography — MRCP does not expose patients to ionizing radiation and does not have the risks of cholangitis and pancreatitis associated with ERCP. In many cases, it is a test of choice for diagnosing and evaluating biliary cysts. Its sensitivity for biliary cysts is between 73 and 100 percent [68]. However, MRCP is less sensitive than direct cholangiography for excluding biliary obstruction. Data are variable with regard to its ability to diagnose an abnormal pancreatobiliary junction: studies report a sensitivity of 0 to 75 percent [39,60,68-70].

ERCP and other forms of direct cholangiography — Direct cholangiography (endoscopic, percutaneous or intraoperative) has a sensitivity of up to 100 percent for diagnosing biliary cysts [71]. It is particularly useful for diagnosing or excluding biliary obstruction and small distal stones and detecting an APBJ [72]. Type III cysts may be first suspected during ERCP, when a dilated intraduodenal portion of the bile duct becomes much more apparent during contrast injection, ballooning in shape as it fills with contrast.

However, ERCP may miss malignant strictures in the proximal portion of a type I or IV cyst, unless attempts are made to cannulate and fill the intrahepatic bile ducts and biliary confluence proximal to the cyst. Complications of cholangiography include cholangitis and pancreatitis [73-75]. Patients with biliary cysts are at greater risk for these complications compared with the general population due to the presence of long common channels, dysfunctional sphincters, and dilated ducts [73]. (See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults" and "Infectious adverse events related to endoscopic retrograde cholangiopancreatography (ERCP)" and "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis" and "Percutaneous transhepatic cholangiography in adults".)

Endoscopic ultrasound — EUS can demonstrate extrahepatic biliary cysts, provide detailed images of the cyst wall and pancreaticobiliary junction, and look for evidence of biliary obstruction. Unlike transabdominal ultrasonography, EUS is not limited by body habitus, bowel gas, or overlying structures. If there is a mass visualized within the cyst, it may be sampled by intraductal biopsy obtained during ERCP or cholangioscopy (See "Pathology of malignant liver tumors", section on 'Cholangiocarcinoma'.).

Intraductal ultrasound (IDUS) has been used for the diagnosis of early malignant changes in a biliary cyst [76]. This technique is likely to be more sensitive than direct cholangiography for detecting early malignancy in the cyst wall. (See "Intraductal ultrasound for evaluating the pancreaticobiliary ductal system", section on 'Cholangiocarcinoma' and "Clinical manifestations and diagnosis of cholangiocarcinoma", section on 'Endoscopic ultrasound'.)

Hepatobiliary scintigraphy — Hepatobiliary scintigraphy can demonstrate continuity of cysts with the bile ducts. This nuclear medicine examination uses a radiolabeled bile salt (technetium-99m-labeled hepatic iminodiacetic acid [HIDA]), which is injected intravenously and is then selectively taken up by hepatocytes and excreted into the bile. In patients with extrahepatic biliary cysts, the characteristic appearance is of an ovoid or spherical photon-deficient area that shows progressive radiotracer accumulation on delayed imaging (>2 hours after injection), with persistent pooling of activity seen for up to 24 hours [77]. This appearance is seen in over 80 percent of extrahepatic biliary cysts. Scintigraphy may also be useful in cases of cyst rupture since excreted contrast may be seen within the peritoneal cavity in these patients [78]. In neonates, biliary scintigraphy can usefully distinguish a choledochal cyst from biliary atresia. (See "Approach to evaluation of cholestasis in neonates and young infants", section on 'Scintigraphy'.)

Direct cholangioscopy — Endoscopic examination of the biliary mucosa can be performed via a percutaneous tract, or by passage of a pediatric gastroscope into the biliary tree via the mouth, or using a choledochoscope passed into the biliary tree via a duodenoscope. Cholangioscopy has an emerging role in the detection of dysplasia in biliary cysts and may be the most sensitive test available for this purpose as it provides direct visualization of the cyst mucosa and facilitates targeted biopsy of visual abnormalities. The advent of high-resolution, disposable cholangioscopes facilitating direct endoscopic visualization of the biliary mucosa at the time of ERCP is likely to change the approach to some choledochal cyst patients, particularly adults who refuse surgery or whose comorbidities increase their operative risk. Case reports demonstrate the feasibility of careful cyst mucosa examination by cholangioscopy, including diagnosis of intestinal metaplasia and imaging features associated with low-grade dysplasia, and the ability to reassess the bile duct postoperatively [79].

DIFFERENTIAL DIAGNOSIS — Biliary cysts should be differentiated from cysts that do not communicate with the biliary tree including pancreatic, mesenteric, and hepatic cysts, and pancreatic pseudocysts. If doubt remains after cross-sectional imaging (CT or magnetic resonance cholangiopancreatography [MRCP]), hepatobiliary scintigraphy, EUS or ERCP can be performed to confirm that the cyst communicates with the biliary tree. (See 'Hepatobiliary scintigraphy' above and 'ERCP and other forms of direct cholangiography' above.)

Acute or chronic biliary obstruction may cause marked biliary dilation that mimics a type I cyst. Such patients usually present with jaundice or elevated serum liver tests, have a readily identifiable obstructing lesion such as a stone, stricture, or mass, and their biliary dilation often improves after appropriate treatment [80]. A careful evaluation for an abnormal pancreatobiliary junction (eg, with ERCP) may help with diagnosis in indeterminate cases. (See 'ERCP and other forms of direct cholangiography' above.)

Biliary cysts are increasingly diagnosed before or soon after birth. While initially suspected on the basis of ultrasound exam, prenatal MRI appears to be highly accurate for confirming the diagnosis. The differential diagnosis in such cases includes cystic biliary atresia, which presents with cystic changes in the hepatic hilum associated with jaundice and atresia of the common duct. Early surgery favorably impacts prognosis of patients with cystic biliary atresia, whereas surgery can be postponed in many neonates with choledochal cysts. Neonates with cystic biliary atresia tend to have higher serum bilirubin concentrations and smaller cystic lesions than neonates with choledochal cysts [81].  

MANAGEMENT — The approach to management of patients with biliary cysts depends on the cyst type. Patients with type I, II, or IV cysts usually undergo surgical resection of the cysts due to the significant risk of malignancy, provided they are good surgical candidates. Serial sections from the cyst wall should be examined by the pathologist to look for any malignant changes. Type III cysts (choledochoceles) require treatment if they are symptomatic and may be managed with sphincterotomy or endoscopic resection in the absence of neoplasia [13]. Treatment for type V cysts is largely supportive and is aimed at dealing with problems such as recurrent cholangitis and sepsis. Type V cysts can be difficult to manage, and some patients with type V cysts eventually require liver transplantation.

Regardless of the type of cyst, patients with ascending cholangitis require treatment with antibiotics and drainage. Drainage of an obstructed and infected bile duct can usually be obtained via endoscopic stent placement, endoscopic nasobiliary drainage, or percutaneous transhepatic biliary drainage. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on 'Management' and "Endoscopic management of bile duct stones" and "Percutaneous transhepatic cholangiography in adults".)

Type I and IV cysts — Complete surgical excision is recommended for type I and IV biliary cysts, with the goal of removing all of the cyst tissue when possible [25]. The approach is advocated because of the risk of malignancy associated with these cysts. In addition to decreasing the risk of malignancy, cyst excision can reduce complications such as recurrent cholangitis, cystolithiasis, choledocholithiasis, and pancreatitis. Surgical treatment by cyst-enterostomy rather than resection is associated with poorer short- and long-term outcomes, with a higher risk of subsequent malignancy [82].

Because there is no histological distinction between a choledochal cyst and the adjacent normal bile duct, the proximal margin of resection is based solely on morphology. The lower resection margin depends on the distal extent of the cyst. Various methods have been proposed to determine the cyst’s lower border, including [83]:

●Preoperative magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and/or ERCP

●Intraoperative cholangiography, choledochoscopy, or ultrasonography

Our approach is to assess the distal extent of the cyst and the anatomy of the pancreaticobiliary junction prior to surgery by MRCP, EUS, and/or ERCP. ERCP may be particularly useful when other tests have not clearly delineated the nature of the pancreaticobiliary junction, or when stones or protein plugs may be present in the common ductal channel requiring endoscopic extraction, or to obtain tissue specimens and/or direct cholangioscopic examination of the bile duct to assess for dysplasia.

Resection of extrahepatic cysts is usually accompanied by Roux-en-Y hepaticojejunostomy to provide biliary drainage from the liver [46,84]. The use of an appendiceal interposition graft has also been reported in children, but the value of this technique has been questioned [85,86]; isolated jejunal interposition loops have also been used in children [87]. In some cases, excision of the cyst may be complicated by its relationship to nearby structures. If dissection of a cyst from the portal vein or hepatic artery is technically difficult, some surgeons advocate leaving the posterior cyst wall intact and performing a mucosectomy (removal of the epithelial lining of the cyst) [46]. The mucosectomy is performed in an attempt to decrease the risk of malignancy.

The relationship of type I cysts to the pancreatic head can also complicate cyst removal. The intrapancreatic portion of type I cysts can generally be treated with intramural dissection of the bile duct down to the pancreaticobiliary junction without pancreatic head resection [88]. If left in place, the intrapancreatic portion of a type I cyst is prone to development of stones or malignancy in the cyst remnant [83,89,90]. Some surgeons favor the endoscopic placement of a pancreatic duct stent prior to surgery in patients whose cyst extends close to the pancreaticobiliary junction to aid in the intraoperative identification of the pancreatic duct. Intraoperative injection of the biliary tree with indocyanine green to enhance visualization of the bile duct and pancreaticobiliary junction, and guide resection of the intrapancreatic portion of a biliary cyst, has also been described [91].

Complete resection of the intrahepatic portion of the cyst may not be technically feasible in some patients with type IV cysts. In one series, long-term outcome of such patients following incomplete cyst resection was good if "proper bile flow" was established surgically (defined as no relative bile duct constriction proximal to or at the biliary anastomoses, and normalization of serum liver tests after surgery), whereas late complications were common in patients not meeting this criterion [92].

Patients undergoing cyst resection before one year of age are at increased risk for long-term complications [93]. For patients whose biliary cyst was diagnosed prenatally, the diameter of the biliary cyst on initial postnatal ultrasound may predict the development of symptoms and need for early cyst excision [94]. The most frequent long-term complication of hepaticojejunostomy is stenosis of the biliary-enteric anastomosis leading to cholangitis, jaundice, or cirrhosis. This complication occurs in up to 30 percent of patients over time [95,96], and patients should be monitored for evidence of stricture formation with annual serum liver tests.

Intrahepatic Type IV cysts — Intrahepatic cysts may be difficult to treat. Patients with type IVA cysts often undergo partial hepatectomy for excision of the intrahepatic portion of the cyst, and reconstruction with wide hilar Roux-en-Y hepaticojejunostomy. However, symptoms may persist due to residual intrahepatic cysts [97]. Partial hepatectomy is advocated by some surgeons to achieve complete resection of type IV cysts, particularly in adults [98]. The Roux limb of a hepaticojejunostomy may be sutured to the abdominal wall (access loop), allowing subsequent percutaneous choledochoscopy via the jejunal limb with stone extractions and dilations [99]. Surgical unroofing of intrahepatic cysts has also been reported [100]. In some cases liver transplantation may be required.

Type II cysts — In some cases, these cysts can be removed with simple excision [25]. Cysts with complicated presentations (including jaundice or malignancy in the cyst) may require more extensive resection [101]. (See 'Cyst type' above.)

Type III cysts — Type III cysts require treatment if they are symptomatic. In addition, asymptomatic type III cysts probably merit treatment in young patients due to the low but real risk of malignancy [13]. Type IIIA cysts are often amenable to endoscopic sphincterotomy [13]. Because malignancy has rarely been reported in type IIIA cysts, endoscopic biopsies of the cyst epithelium should be obtained following sphincterotomy to determine if the cyst is lined by duodenal or biliary mucosa (the latter being associated with an increased risk of malignancy), and to exclude dysplasia. Endoscopic snare resection of type IIIA cysts can be performed [13]. Type IIIB cysts may be resected surgically or endoscopically [102,103].

Type V cysts — As with type IVA cysts, the intrahepatic cysts in patients with type V biliary cysts can be difficult to manage. Treatment for type V cysts is largely supportive and is aimed at dealing with problems such as recurrent cholangitis and sepsis. Some patients with type V cysts will eventually require liver transplantation. The treatment of patients with type V cysts is discussed elsewhere. (See "Caroli disease", section on 'Management'.)

Type VI cysts — Little data is available to guide management of these rare cysts, but it seems reasonable to advise complete cyst resection given the association of types I and IV cysts with malignancy.  

Laparoscopic and robotic surgery — Observational studies from high-volume centers demonstrate the efficacy and safety of minimally invasive surgical techniques for resection of types I and IV cysts, including children and infants. Laparoscopic methods appear to have similar success and adverse event rates compared with open surgery [104]. Single-port umbilical laparoscopic cyst resection and "scarless" approaches via trochar placements in the Pfannenstiel line have been described. Robotic surgery was associated with quicker recovery and fewer adverse events compared with laparoscopic surgery [105].

Timing of surgery in neonates and infants — Cyst resection should ideally be performed before symptoms develop or complications of disease occur. In one pediatric series, a serum gamma-glutamyl transpeptidase (GGT) level >346.5 U/L was associated with impending choledochal cyst rupture [106]. Other studies suggest that infants with choledochal cysts are more likely to have symptoms when their cyst length is >5.2 cm or cyst width is >4.1 cm [107].

Abnormal pancreaticobiliary junction — Patients with an abnormal pancreatobiliary junction (APBJ) and no biliary cyst should undergo prophylactic cholecystectomy because of the increased risk of gallbladder cancer. (See "Gallbladder cancer: Epidemiology, risk factors, clinical features, and diagnosis", section on 'Abnormal pancreaticobiliary duct junction'.)

Patients with an abnormal pancreatobiliary junction and a dilated common channel may develop proteinaceous plugs or stones within the common channel, resulting in ductal obstruction and pancreatitis. In such patients, cyst resection alone may not lead to symptom resolution. Surgical or endoscopic removal of stones or protein plugs from the common channel and surgical sphincteroplasty or endoscopic sphincterotomy may also be required.

Patients who have undergone cystenterostomy — In the past, some patients with type I or IV biliary cysts were treated with internal drainage via a cystenterostomy. While effective at treating symptoms, the procedure was associated with significant complications such as ascending cholangitis due to reflux of enteric contents into the cyst and biliary tree, anastomotic stricture formation, and most importantly, a 30 percent postoperative risk of malignancy [99,108]. Patients who have previously undergone cystenterostomy should undergo surgery to completely remove the cyst, if possible.

Alternatives to surgery — In patients with type I, II, or IV biliary cysts who refuse surgical resection or who are poor surgical candidates, lesser interventions (such as laparoscopic cholecystectomy, endoscopic sphincterotomy, or endoscopic stent placement) may treat symptoms caused by gallstones or sludge. There is no proven effective method of screening biliary cysts for dysplasia or intramucosal cancer. If screening is attempted, direct cholangioscopy is probably the most sensitive test for detecting early malignancy in the cyst mucosa; intraductal ultrasound may also be useful. A less invasive approach is to perform periodic MRI with contrast and MRCP, but this may be less likely to detect in situ neoplasia. Appropriate intervals for periodic reassessment of the biliary mucosa in such patients have not been defined. (See "Intraductal ultrasound for evaluating the pancreaticobiliary ductal system", section on 'Cholangiocarcinoma'.)

PATIENT FOLLOW-UP — While the carcinoma risk is decreased in patients who have undergone cyst resection, these patients continue to be at increased risk of carcinoma in the remaining biliary tree and pancreas compared with the general population. Overall, subsequent malignancy develops during long-term follow-up in about 2 percent of patients who previously underwent cyst resection with hepaticojejunostomy [109], and the risk is higher in patients who have undergone partial cyst resection. Patients treated with cyst enterostomy rather than resection had an 18 percent risk of malignancy during follow-up in one meta-analysis [109]. Post-excisional malignant disease is seen in 0.7 to 6 percent of patients. Malignancy may develop in portions of cysts that were left behind at surgery, including distal cyst stumps within the pancreatic head, or at the biliary anastomotic site, or in the pancreas [47,48,110-112].

The appropriate follow-up for patients who have been treated for a biliary cyst is unclear. The purpose of follow-up is to detect evolving anastomotic stenosis, intraductal stone formation, and/or resectable metachronous malignancy. On the basis of a systematic review, one group of investigators proposed annual serum liver tests and CA 19-9 measurement and biannual ultrasound assessment for 20 years after resection of types I and IV cysts, with biannual serum liver tests and three yearly ultrasound assessments thereafter [113]. While these recommendations are reasonable, their benefit is unproven.

For patients who have undergone partial cyst excision or who refuse cyst excision, the value of periodic imaging tests to screen for malignancy is unproven. It is reasonable to consider yearly imaging studies (MRI with intravenous contrast and magnetic resonance cholangiopancreatography, intraductal ultrasound, or direct cholangioscopy) in such patients to assess for early malignant change if findings will alter patient management. For those with type III cysts treated with endoscopic sphincterotomy, it is reasonable to perform endoscopic biopsies of the cyst mucosa, both at the time of sphincterotomy and a year later, to assess for dysplasia. Patients with malignancy in the resected cyst may require additional treatment and follow-up. (See "Adjuvant and neoadjuvant therapy for localized cholangiocarcinoma".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hepatic and biliary cysts".)

SUMMARY AND RECOMMENDATIONS

●Biliary cysts are cystic dilations that may occur singly or in multiples throughout the biliary tree. Biliary cysts can lead to significant complications such as ductal strictures, stone formation, cholangitis, secondary biliary cirrhosis, rupture, and cholangiocarcinoma. (See 'Introduction' above.)

●The classification scheme for biliary cysts takes into account cyst location, cyst number, and whether there is an abnormal pancreaticobiliary junction (figure 1). (See 'Types of biliary cysts' above.)

●The classic presentation of a biliary cyst includes the triad of abdominal pain, jaundice, and a palpable mass. However, the majority of patients will only have one or two elements of the triad. Patients may also report nausea, vomiting, fever, pruritus, and weight loss. Biliary cysts may also be an incidental finding during prenatal ultrasonography or in an asymptomatic patient who is undergoing imaging or endoscopic retrograde cholangiopancreatography (ERCP) for other reasons. (See 'Clinical manifestations' above.)

●Biliary cysts are associated with an increased risk of cancer, particularly cholangiocarcinoma. Overall, the incidence of cancer is reported to be in the range of 10 to 30 percent, though published reports may overestimate the true incidence. Cancer is more common in patients who are older and in those with type I and IV cysts. The possibility of cancer should always be considered in an adult with a newly diagnosed biliary cyst. (See 'Cancer risk' above.)

●Biliary cysts are typically diagnosed by cross-sectional imaging. Additional testing may be required to rule out biliary obstruction (ERCP or endoscopic ultrasound) or to confirm communication of the cyst with the biliary tree (hepatobiliary scintigraphy or ERCP). (See 'Diagnosis' above.)

●The management of patients with biliary cysts depends on the cyst type and whether the patient has symptoms. For cysts with high malignant potential, resection decreases (but does not eliminate) the risk of malignancy. In addition to decreasing the risk of malignancy, the excision of cysts can reduce complications such as recurrent cholangitis, choledocholithiasis, and pancreatitis. (See 'Patient follow-up' above.)

•For patients with type I or IV cysts, we recommend complete surgical excision of the cyst with Roux-en-Y hepatojejunostomy rather than expectant management (Grade 1B). Type I and IV cysts have a high risk of malignancy if left in place. (See 'Type I and IV cysts' above and 'Cancer risk' above and 'Patient follow-up' above.)

•For patients with type II cysts, we suggest simple excision of the cyst rather than expectant management (Grade 2C). (See 'Type II cysts' above.)

•For patients with type III cysts, we suggest treatment of symptomatic cysts as well as asymptomatic cysts in young patients, rather than treating all patients (Grade 2B). Sphincterotomy is often sufficient to relieve symptoms but should be accompanied by biopsy of the cyst epithelium to determine if the cyst is lined by duodenal or biliary mucosa (the latter being associated with an increased risk of malignancy), and to exclude dysplasia; alternatively, endoscopic or surgical resection may be performed. (See 'Type III cysts' above.)

•Treatment for type V cysts is largely supportive and is aimed at dealing with problems such as recurrent cholangitis and sepsis. Type V cysts can be difficult to manage, and some patients with type V cysts eventually require partial hepatic resection and/or liver transplantation. (See "Caroli disease", section on 'Management'.)

•For patients with no cyst but an abnormal pancreatobiliary junction, we suggest prophylactic cholecystectomy rather than expectant management (Grade 2C). Patients with an abnormal pancreatobiliary junction are at increased risk for gallbladder cancer. (See 'Abnormal pancreaticobiliary junction' above.)

●For those who have undergone total cyst excision, we perform annual measurement of serum liver tests and CA 19-9 and transabdominal ultrasound to detect evolving anastomotic stenosis, intraductal stone formation, and/or resectable metachronous malignancy. For those who have undergone partial cyst excision or who refuse cyst excision, the value of periodic imaging tests to screen for malignancy is unproven, but it is reasonable to consider yearly imaging studies (MRI with intravenous contrast and magnetic resonance cholangiopancreatography, intraductal ultrasound, or direct cholangioscopy) in such patients to assess for early malignant change if findings will alter patient management. For those with type III cysts treated with endoscopic sphincterotomy, it is reasonable to perform endoscopic biopsies of the cyst mucosa, both at the time of sphincterotomy and a year later, to assess for dysplasia. Patients with malignancy in the resected cyst may require additional treatment and follow-up. (See 'Patient follow-up' above.)