Original contributionCholedochal cysts: a clinicopathologic study of 36 cases with emphasis on the morphologic and the immunohistochemical features of premalignant and malignant alterations☆
Introduction
Choledochal cysts (CDCs) are rare pathologic dilatations of the biliary tract. They predominantly present in children, with only 20% to 30% of the patients being older than 20 years [1]. However, the diagnosis of CDCs has become more frequent in adults, most likely because of improvements in noninvasive hepatobiliary imaging [2].
CDCs are very rare in Western countries, with an estimated incidence of 1 in 13 500 in the United States. They are far more common in the Asian population, with a reported incidence of 1 per 1000 in Japan [3], [4]. They are also more common in females, with a female-to-male ratio of 3.5 to 1 [1].
CDCs are predominantly extrahepatic, in the common bile duct; but they can also involve any part of the biliary tract, including the intrahepatic bile ducts [1].
They are classified based on their anatomic location and the extent and shape of the cystic lesion. In 1959, Alonso-Lej et al [5], [6] proposed a classification for extrahepatic bile ducts cysts, which was later modified by Todani et al [5], [6] to incorporate the intrahepatic dilatations. According to the Todani classification, which is a widely used classification, there are 5 types of CDCs (Fig. 1) [1], [6], as follows: type I, solitary extrahepatic cyst (Ic, cystic type; If, fusiform type); type II, extrahepatic supraduodenal diverticulum; type III, intraduodenal diverticulum; type IV, extrahepatic and intrahepatic dilatation (IVa, fusiform extrahepatic and intrahepatic cysts; IVb, multiple extrahepatic cysts); and type V, multiple intrahepatic cysts (Caroli disease). Except for type IV cysts, which are seen more frequently in adults, the cyst types are equally distributed among children and adults [7], [8], [9]. Type I is the most common (79%), followed by type IV (13%), type III (4%), type II (3%), and type V (1%) [10].
Nevertheless, the Todani classification puts together different diseases with different etiology and pathogenesis and might be oversimplified. In 2004, Visser et al [11] suggested that the distinction between Todani type I and type IV cysts is arbitrary because the intrahepatic ducts are never completely normal and that types I and IV are the same process, type III is choledochocele, and type V is Caroli disease.
The classic triad of jaundice, abdominal mass, and pain occurs less commonly in adults with CDCs than in children. Adults usually present with vague symptoms; however, the symptoms in adults appear to be more serious, with a higher rate of cholangitis, pancreatitis, and cholecystitis than in pediatric patients [3], [12]. CDCs may be associated with a variety of complications such as stones, inflammation, infections, and obstruction [3]. Moreover, they have been associated with increased risk of malignancy both in the bile ducts and in the gallbladder [4], [13]. Presumably, the evolution of carcinoma in CDCs follows a similar sequence of dysplasia (biliary intraepithelial neoplasia [BilIN]) as described in the noncystic bile ducts [7], [14]; but extensive pathologic studies have not been performed.
In this study, we examined 36 cases of CDC resected at a single North American institution, focusing on the morphologic features of these lesions including different types of metaplasia, BilIN, and carcinoma. We also analyzed the immunohistochemical features of the premalignant and malignant alterations in these lesions.
Section snippets
Materials and methods
After obtaining Institutional Review Board approval on September 2008, all identifiable cases of CDCs were retrieved from the files of the Department of Pathology at Memorial Sloan-Kettering Cancer Center, dating from 1990 to 2008. Hematoxylin and eosin–stained sections were available in 36 cases. The cystic lesions were well sampled: 88% of the cysts had at least 1 sampled section per centimeter size. The cyst size was reported. The cyst type, based on the anatomic site using the Todani
Clinical and anatomic findings
The clinical and anatomic features of the CDCs are displayed in Table 2.
The age of the patients ranged from 11 to 67 years old (mean, 36 years). Thirty of 36 patients were female (female-to-male [F/M] ratio of 5:1). The majority of patients were white (29/36). The size of the cysts ranged from 0.9 to 11.5 cm in greatest dimension (mean, 4.4 cm). The cysts were classified based on their anatomic site using the Todani classification as follows: type I, 71%; type II, 8.5%; type IV, 14%, and type
Discussion
CDCs are rare congenital anomalies that have been associated with an increased risk of malignancy in both the gallbladder and bile ducts [1], [4]. CDCs are far more common in the Asian population, and data are still quite limited regarding carcinogenesis of these rare lesions in Western countries. In this study, we identified 36 cases of CDCs resected at a single institution in North America and studied their clinical, histopathologic, and immunohistochemical features. To our knowledge, this
References (28)
- et al.
Benign and malignant tumors of the gallbladder and extrahepatic biliary tract
- et al.
Long-term consequence of endoscopic sphincterotomy for bile duct stones
Gastrointest Endosc
(1998) - et al.
Congenital bile duct cysts: classification, operative procedures, and review of thirty-seven cases including cancer arising from choledochal cyst
Am J Surg
(1977) - et al.
Metaplastic lesions of the extrahepatic bile ducts: a morphologic and immunohistochemical study
Mod Pathol
(2001) - et al.
MUC 1 core protein as a marker of gallbladder malignancy
Eur J Surg Oncol
(2005) - et al.
Choledochal cyst and associated malignant tumors in adults: a multicentric survey in South Korea
Arch Surg
(2011) - et al.
Bile cysts in adults
Br J Surg
(2004) - et al.
Congenital choledochal cyst, with a report of 2, and an analysis of 94, cases
Int Abstr Surg
(1959) - et al.
Tumors of the gallbladder, extrahepatic bile ducts, and ampulla of Vater
Atlas of tumor pathology. 3rd series
(2000) - et al.
Choledochal cysts—differences in children and adults
Br J Surg
(1996)
Histochemical and immunohistochemical studies on development of biliary carcinoma in forty-seven patients with choledochal cyst—special reference to intestinal metaplasia in the biliary duct
Jpn J Surg
Choledochal cysts in adults: clinical management
Surgery
Congenital choledochal cysts in adults
Arch Surg
Bile duct cyst as precursor to biliary tract cancer
Ann Surg Oncol
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The authors declare that there is no conflict of interest.