Cholangiocarcinoma arising in von Meyenburg complexes: Report of four cases

Abstract

Although von Meyenburg complexes (VMC) are largely considered to be innocuous, neoplastic transformations have been described. The present report describes four cases of cholangiocarcinoma (CC) occurring on a background of VMC. The patients were all male and aged 69, 59, 68 and 75 years, respectively. While two patients were asymptomatic, the other two had a history of colon cancer. Radiologically the tumors measured 3, 4, 4.5 and 10 cm and were well enhanced from the arterial to delayed portal phase. Microscopically, the tumor consisted of multiple foci of characteristic VMC, and had a gradual transition from VMC to hyperplasia or dysplasia and well‐ to moderately differentiated adenocarcinomas. One patient had combined hepatocellular carcinoma (HCC) and CC, occurring in the high grade dysplastic nodule and VMC. On immunohistochemistry the epithelial cells of the VMC and CC were immunopositive for cytokeratin (CK) 7 in three patients, with another patient being focally positive only for CK19. The Ki‐67 labeling indices increased from the VMC to the dysplastic areas and then to the carcinomas. As a potentially precancerous lesion, VMC should be carefully followed up in terms of any size increases. Thus, biopsies are essential to determine any proliferative epithelial changes including dysplasia and malignant transformation.

Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma

“…VMCs are thought to result from persistence of the embryonic ductal plate and are generally adjacent to portal areas [1] . Multiple case reports showed exist of VMCs with histologic evidence of transformation to cholangiocarcinoma, showing benign, hyperplastic and dysplastic epithelium with adjacent progression to invasive carcinoma [7,8,38,39] . These lesions are fairly common with prevalence of 5.6% in adults and 0.9% of children in one autopsy series, and are especially prevalent in patients with adult polycystic kidney disease or congenital hepatic fibrosis [40] .…”

“…No intraepithelial or intraductal preneoplastic, dysplastic or neoplastic lesions have been demonstrated in the small bile ducts or ductules [5] . Von Meyenburg complex (VMC) is suggested to be a possible premalignant lesion of ICCs due to the occasional association of VMC with ICCs and reports of VMC-like cystic ICCs [6][7][8] . Progression of bile duct adenoma (BDA) to ICC has also been reported [9] .…”

Calcification in biliary hamartomatosis

“…Tohme-Noun et al [1] found elevated serum levels of gamma-glutamyltranspeptidase (GGT) that could not be explained by another disease in 4 out of 11 patients with histologically proven hamartomatosis. The prevalence of biliary hamartomas has been estimated at 5.6% in adults and 0.9% in children [1,2]; the rate increases with age and chronic liver disease [7]. Biliary hamartomas can be confused with metastases, microabscesses, cysts, biliary adenomas, dilated bile ducts [4], cirrhosis [8,9], granulomatous hepatitis [8] and cystadenocarcinoma [10].…”

“…Microscopic examination reveals that they are composed of a variable number of disorganised irregular tiny bile ducts immersed in fibrocollagenous stroma that may be hyalinised [11]. The ductal structures have a variable degree of dilation, can contain viscous bile [2] and do not communicate with the normal terminal bile ducts [5]. When the ducts dilate, they may coalesce in cystic cavities with intracavitary persistence of surrounding connective tissue forming endocystic polypoid projections [1].…”

“…Biliary hamartomas are rare, benign malformations of the intrahepatic bile ducts [1]; they were first described by von Meyenburg in 1955 [2] and are also known as von Meyenburg complexes [3,4], microhamartomas, adenomas of the small bile ducts, cholangioadenomas, intracapsular aberrant bile ducts, fibroadenomatosis and liver hamartomatosis [5]. Biliary hamartomas are considered part of the spectrum of fibropolycystic liver disease arising from abnormal embryological development of the ductal plate [3,6] (the cylindrical layer of cells that surrounds the portal branch and then gives rise to the bile ducts), which also includes congenital liver fibrosis, Caroli's disease, mesenchymal hamartomas, dominant autosomal polycystic disease and choledochal cysts.…”