A complicated peribiliary cyst: An unusual hilar cholangiocarcinoma mimic

Oriana Barrios , Kristel Mils , Laura Lladó, Josefina Lopez-Dominguez , Emilio Ramos

Division of Hepatobiliary Surgery, Bellvitge University Hospital, Barcelona 08907, Spain

TotheEditor:

Peribiliary cysts are cystic dilatations of the extramural peribil- iary glands that appears in the connective tissue around the hep- atic hilum. They can affect up to the fourth order intrahepatic bile ducts and do not communicate with the bile lumen. It is a rare entity first described in 1984 by Nakanuma et al. [1] . Its diagnosis is usually an incidental discovery in patients with advanced liver disease, portal thrombosis, and portal hypertension [2] .

The clinical importance of this entity lies in the fact that it should be included in the differential diagnosis in patients with obstructive jaundice and alcoholic habit and/or chronic liver dis- ease [ 2 , 3 ].

We present the case of a 77-year-old man with chronic alco- holic liver disease history who was admitted in another hospital with symptoms and signs of acute cholangitis. Empirical antibi- otic treatment was started and hilar cholangiocarcinoma was diag- nosed. With this diagnosis, he was referred to our center to com- plete the treatment.

Laboratory findings showed a highlighted elevation of the gamma-glutamyltransferase (1080 U/L), alkaline phosphatase (300 U/L) and carbohydrate antigen 19-9 (CA19-9) (18 313 U/L), with normal bilirubin level (7 μmol/L). Hepatitis viral serologic results were negative.

Computed tomography (CT) showed changes of chronic liver disease, with the presence of multiple peribiliary cysts, predomi- nantly central and in segment II of the liver. A bile duct dilatation corresponding to the right anterior sector and segments II and III was also observed, without being able to confirm a clear obstruc- tive tumor lesion ( Fig. 1 A). No signs of tumor spread were identi- fied.

A magnetic resonance imaging (MRI) of the liver and a mag- netic resonance cholangiopancreatography (MRCP) confirmed an intrahepatic bile duct dilatation on the right anterior segment and on the segments II and III, with beaded bile ducts up to the primary biliary confluence where they were abruptly interrupted ( Fig. 1 B); likewise, in the pancreas, the presence of several infra- centimetric cystic formations distributed throughout its length was demonstrated, except for one located in the distal portion of the body, measuring 41 × 35 mm, which did not restrict diffusion or show contrast uptake in its interior, suggesting intraductal papil- lary mucinous neoplasm (IPMN).

The diagnosis was completed with a positron emission tomog- raphy (PET-CT) that revealed a small hypermetabolic lesion consis- tent with hilar neoplasia (SUVmax 4.5) ( Fig. 1 C). Likewise, a het- erogeneous increase in glycidic metabolism of the bile ducts was observed, especially in segment II, with small periportal and celiac hypermetabolic lymph nodes suggesting malignancy ( Fig. 1 C).

Due to the diagnostic suspicion of hilar cholangiocarcinoma with pathological lymph nodes, an endoscopic ultrasound was re- quested. During this procedure, for cytology study a sample was obtained by lymph node puncture, which did not confirm the pres- ence of adenocarcinoma.

During the study period, a spontaneous improvement of the cholestasis in the blood analysis and a decrease in CA19-9 level to 1587 U/L were observed. A new PET-CT performed one month after the initial one, showed an absence of pathological deposits of fluorodeoxyglucose (FDG) in the region of the biliary confluence. Due to these findings, the diagnosis was reconsidered and it was contemplated that an inflammatory or infectious complication of a peribiliary cyst was the possible cause of the initial jaundice and the cholangitis. Likewise, we believed that bilirubin levels were not high, because as evidenced in the MRCP, the right posterior bile ducts were not dilatated and this could be translated into good bil- iary drainage.

The patient was discharged from hospital to follow up on out- patient visits. After a 2-year follow-up, the patient remained clin- ically asymptomatic, with a normal level of CA19-9 tumor marker and global stability of the peribiliary cysts ( Fig. 2 ).

Fig. 1. A: CT in portal venous phase showing peribiliary cysts in segment II; B: MRCP showing intrahepatic bile duct dilatation on the right anterior segment as well as for segments II and III of the left bile duct until their confluence; C: 18 F-FDG PET-CT showing hypermetabolic solid lesion in the hepatic hilum (SUVmax 4.5). CT: computed tomography; MRCP: magnetic resonance cholangiopancreatography; FDG: fluorodeoxyglucose; PET: positron emission tomography.

Fig. 2. MRCP at 2 years of follow-up showing peribiliary cysts size stable. MRCP: magnetic resonance cholangiopancreatography.

Nowadays, the peribiliary cysts pathogenesis remains unclear; two main theories have been proposed. The first one is related to a chronic inflammatory and/or circulatory imbalance, that occurs in portal hypertension and can lead to cysts formation. The second mechanism attributes to genetic factors in autosomal dominant diseases such as polycystic liver disease [4] . Bazerbachi et al. [2] , in a systematic review that included 135 patients, showed that only 15% of the cases were idiopathic without recognized associ- ated pathology, while up to 38% of the patients had liver cirrhosis, 36% portal hypertension, among other associations.

The presence of peribiliary cysts has been suggested to be related to liver inflammation and fibrosis induced by alcohol abuse [3] . Both histopathological alterations would be responsible for the duct obliteration that communicates the peribiliary glands with the bile ducts and secondarily would cause a cystic dilatation of these glands [2] .

In 2014, Matsubara et al. [3] , in a 209 autopsies series in patients with chronic alcoholic liver disease, found out that the prevalence of peribiliary cysts in this population was 14.4%. Its fre- quency was correlated with the degree of liver fibrosis, suggesting a pathogenic relationship [ 3 , 5 ].

Most patients remain asymptomatic [ 2 , 6 ], but in some cases, jaundice, cholangitis due to biliary stasis, hepatolithiasis, pancre- atitis and infection of a peribiliary cyst may appear [2] in as- sociation with elevated tumor markers such as carcinoembryonic antigen and CA19-9. The increment of CA19-9 is related to bil- iary obstruction due to peribiliary cysts more than to the cysts themselves [7] .

業(yè)務層面控制是內部控制具體實施，是各種控制措施和要求的集成，為達到特定的目標而由不同的崗位分別共同完成的一系列活動。活動之間不僅有嚴格的先后順序限定，而且活動的內容、方式、責任等也都必須有明確的安排和界定，以使不同活動在不同崗位之間進行轉接成為可能，構成閉環(huán)系統(tǒng)。目前，業(yè)務層面控制活動一般應包括：生產(chǎn)、銷售、采購、成本、資金、資產(chǎn)、工程、擔保、合同、信息管理等方面?？刂拼胧┮话銘ǎ翰幌嗳萋氊煼蛛x控制、授權審批控制、會計系統(tǒng)控制、財產(chǎn)保護控制、計劃控制、預算控制、合同管理控制、資金支付控制、信息技術控制、運營分析控制和績效考評控制等，每一項控制措施獨立或組合用于各類活動中。

Imaging diagnosis can be performed by CT or MRCP to confirm cystic lesions adjacent to the portal branches and the absence of communication of the cysts with the lumen of the bile ducts [8] . For its part, PET-CT is useful to rule out an associated neoplastic process [4] ; it even seems to contribute to the diagnosis and local- ization of a complicated peribiliary cyst, as it was in our case.

In patients with advanced chronic liver disease, asymptomatic peribiliary cysts do not require any therapeutic measures. However, when there is jaundice or bile ducts dilation, it is necessary to rule out other causes of biliary obstruction before attributing the afore- mentioned alterations to the peribiliary cysts themselves, since the compressive effect of this can simulate other pathologies such as primary sclerosing cholangitis or a cholangiocarcinoma [4] .

In the absence of advanced liver disease, patients with asymp- tomatic peribiliary cysts should go under follow-up, because cysts can progress over time in up to 37.5% of patients [3] ; while in symptomatic cases it has been described that the resolution of bil- iary obstruction can be achieved by fenestration of the obstructive cysts [9].

On the other hand, Umemura et al. [10] related peribiliary cysts with intraepithelial biliary neoplasms, and described their pres- ence as necessary so that these intraductal microscopic biliary dys- plasias can degenerate into a cholangiocarcinoma.

The correct diagnosis of peribiliary cysts and the knowledge of their possible complications remain a challenge, but it is impor- tant to avoid a misdiagnosis of malignant bile duct pathology [2] . In patients with advanced liver disease, this error could delay or contraindicate a liver transplantation [ 4 , 8 ].

Acknowledgments

None.

CRediTauthorshipcontributionstatement

OrianaBarrios:Conceptualization, Data curation, Formal anal- ysis, Investigation, Writing - original draft, Writing - review & editing.KristelMils:Conceptualization, Supervision, Validation, Writing - review & editing.LauraLladó:Supervision, Validation.JosefinaLopez-Dominguez:Supervision.EmilioRamos:Investiga- tion, Supervision, Writing - review & editing, Validation, Visualiza- tion.

Funding

None.

Ethicalapproval

This study was approved by the Clinical Research Ethics Com- mittee of the Bellvitge University Hospital.

Competinginterest

No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the sub- ject of this article.