Association between gallbladder agenesis and choledochal cyst: cause or coincidence?

Abstract

This case report describes an extremely rare association between gallbladder agenesis and choledochal cyst (CC). A 9-year-old girl presented with recurrent abdominal pain in the right upper quadrant. Radiological studies revealed a CC type IVa and an agenesis of gallbladder and cystic duct. Due to the possibility of biliary neoplasm, the patient underwent cyst resection and hepaticoduodenostomy. Histopathological findings showed inflamed fibrous tissue covered by biliary epithelium with no evidence of malignancy.

Background

Gallbladder agenesis (GA) is a rare anomaly of the extrahepatic biliary tract with an estimated incidence ranging between 0.01% and 0.06%.¹ While approximately 35% of the cases are asymptomatic, GA in symptomatic patients is typically discovered in the second or third decade of their life.^{1 2} Both clinical presentation and radiological findings may mimic other biliary diseases, which can lead to misdiagnosis and improper treatment.^1–3 Due its rarity and the non-specific nature of the symptoms, diagnosis of GA appears particularly challenging in children. Additional malformations have been found in one-third of the cases of GA.4. The association of GA and choledochal cysts (CC) is extremely rare and there are less than 10 cases reported in the literature.^{3 4} To our knowledge, this is the first paediatric case reported in the literature.

Case presentation

We presented a 9-year-old girl that refers recurrent abdominal pain in the right upper quadrant. No other symptoms were associated. Neither distention nor tenderness was seen on abdominal examination. Laboratory tests performed showed inflammatory markers, serum amylase, bilirubin levels and liver enzymes within normal limits. Abdominal ultrasonography showed a dilated extrahepatic bile duct and absence of gallbladder.

Investigations

A magnetic cholangioresonance was realised, this evidenced a 5.8 mm dilatation of the left hepatic duct and 7 mm dilatation of the common bile duct (CBD). These findings were suggestive of CC type IVa, according to Todani’s classification. No ectopic gallbladder was found in the lesser omentum, within the falciform ligament or in the intrahepatic, retrohepatic, retroduodenal and retroperitoneal areas. The pancreaticobiliary junction was normal. Therefore, the absence of the gallbladder and the cystic duct was confirmed (figure 1).

Figure 1.

Gallbladder agenesis and choledochal cyst type IVa (arrows) in an axial section of magnetic cholangioresonance.

Treatment

The patient underwent three-dimensional laparoscopic surgery. The gallbladder was not found in its normal location and CBD was dilated (figure 2). We performed cyst resection and hepaticoduodenostomy, after an extended mobilisation of the duodenum, as far distal from the pylorus as possible to avoid postoperative complications.

Figure 2.

Dilated common bile duct during laparoscopic surgery.

Outcome and follow-up

Oral intake was started after 4 days from surgery and the patient was discharged home following 8 days of surgery. Histopathological examination revealed inflamed fibrous tissue covered by biliary epithelium with no evidence of malignancy. After 12 months of follow-up, she is asymptomatic.

Discussion

Congenital absence of the gallbladder and cystic duct is a very rare embryological anomaly.^1–4 The true incidence of GA is unknown, has been reported that ranges from 0.01% to 0.06% in live births and 0.035%–0.3% in autopsy findings.^{2 3} Generally, GA has a peak incidence in the second to third decade of life with a female predominance among symptomatic cases.^{1 2} CC are uncommon bile duct malformations, which can involve both extrahepatic and intrahepatic biliary system.^{3 4} According to Todani’s classification, the most frequent types of CC are I (80%–90%) and IV (15%–20%). CC type IVa extends from the CBD into the intrahepatic biliary system. Most often there is bilobar involvement, although dilatation of the left lobe is the second most common presentation.⁵ The incidence of CC varies with geographic location, ranging from 1 in 13 000 live births in Asia to 1 in 100 000–150 000 live births in Western countries. Five CCs are usually diagnosed within the first decade of life and, as with GA, there is a female predominance.^{4 5} The coexistence of both GA and CC has only been reported in a few cases in adults.3 4 6–8 CC types I, IV and V have been associated with GA; however, the combination of CC type II or III and GA has not been described (table 1).

Table 1.

Cases of choledochal cyst and gallbladder agenesis reported in the literature

No case	Year	Author	Patient’s age (years)	Patient’s gender	Type of choledochal cyst
1	1994	Goel	Unknown	Unknown	IV
2	2009	Tabibian	82	Female	I
3	2011	Compoginis	54	Male	V
4	2012	Böyük	42	Female	I
5	2013	Bedi	56	Female	I

The aetiology of GA is attributed to an abnormality in embryonic development. Gallbladder and biliary system begin to develop around the fourth week of pregnancy as a ventral bud (hepatic diverticulum) from the caudal part of the foregut.^{1 9} Whereas this hepatic diverticulum grows, it divides into two different parts: the primordium of the liver, and the primordium of the gallbladder and bile ducts. In the seventh week, a vacuolisation occurs and the gallbladder and cyst ducts lumen develops.^{1 4 9} Failure of this process at any stage results in GA, whereas failure of migration of the gallbladder primordium results in an ectopic gallbladder. Possible ectopic locations are intrahepatic, retrohepatic, retroduodenal, retropancreatic, retroperitoneal, between the leaves of the lesser omentum or within the falciform ligament.¹ Although there are reports in which GA has presented in several members of the same family, no genetic cause has been identified.^{4 9}

Several hypotheses, either congenic or acquired, have been proposed regarding the pathogenesis of CC.^{4 6} One of the main theories suggests that an abnormal pancreaticobiliary duct junction leads to pancreatic reflux, increased pressure and dilatation of the biliary tree.⁴ It has been also suggested that CC can be associated with enlargement of intrahepatic bile ducts secondary to biliary stasis.⁵ This theory leads us to think that the development of CC in our patient can be secondary to biliary stasis due to the GA.

Bennion et al have categorised GA into three groups according to clinical presentation in 1988: children with multiple fetal anomalies (15%–16%), asymptomatic or incidental finding (35%) and symptomatic (50%).² GA can appear as an isolate defect in 70%–87% of cases (31.6% asymptomatic and 55.6% symptomatic). Additional anomalies occur in the remaining 12%–30% of cases, which can be divided into two groups: those with biliary atresia or CCs (9%) and those with normal bile ducts but multiple congenital malformations (12%–21%).^{4 9} Cardiovascular malformations are the most common associated anomalies.² Right upper quadrant pain is described in more than 90% of symptomatic patients. Other symptoms such as nausea and vomiting, food intolerance, jaundice or dyspepsia tend to be less frequent.³ It has been postulated that these symptoms can be secondary to bile stasis. Patients with GA often have a dilated hepatic duct that takes up the role of bile storage, which predisposes to cholestasis, infection and duct stones.¹⁰

The classic triad presentation of CC is abdominal pain, jaundice and abdominal mass; although clinical presentation usually depends on age.³ Abdominal pain is the most common symptom in paediatric patients with CC.¹¹ CC can be associated with congenital cardiac anomalies and biliopancreatic malformations (cholangitis, hepatic fibrosis, pancreatic cyst, annular pancreas).⁵ Symptoms and complications of patients with CC are usually related to the dilated bile ducts and the abnormal bile dynamics, as occurs in those with GA.

It is well known that early surgical treatment of CC is recommended to avoid the risk of complications such as pancreatitis, choledocholithiasis or cholangiocarcinoma.¹¹ Malignant transformation is most commonly associated with CC type I and IV and it must be associated with chronic inflammation of the biliary tree.¹² Interestingly, Kim et al have reported a case of intrahepatic biliary intraductal papillary mucinous neoplasm in a patient with GA. They suggested that bile stasis may have caused chronic inflammation of the bile duct and this resulted in biliary neoplasm.¹³ A cholangiocarcinoma has also been reported in a patient with GA.¹⁴ We were faced with a therapeutic dilemma for this case. Due to the slight dilatation of the left hepatic duct and CDB, we might have considered conservative management and follow-up. In addition, adult patients with GA often have a dilated hepatic duct and they do not undergo surgical treatment. However, due to the possibility of biliary neoplasm in patients with GA and biliary tree dilatation, we think that cyst excision and bilioenteric reconstruction is the best option.

Learning points.

• The development of choledochal cyst in patients with gallbladder agenesis (GA) can be secondary to biliary stasis.

• Malignant transformation can be associated with chronic inflammation of the biliary tree.

• Surgical treatment should be considered in pateints with chronic biliary tree dilatation and GA.