April 2022 – Liver Pathology

Segmental cholangiectasia/recurrent pyogenic cholangitis.

The patient is a 43-year-old man with intermittent abdominal pain and fevers over the past two years. His MRI showed a gallbladder fundus mass with accompanying left hepatic atrophy, clinically suspicious for a cholangiocarcinoma. Cholecystectomy and liver 4B and 5 segmentectomy were performed. The liver appeared non-cirrhotic. An intraoperative cholangiogram showed common bile duct and intrahepatic duct with a serrated appearance.

The gross pathologic examination of the gallbladder showed hemorrhagic sludgy material. The fundus wall was thickened but there was no mass lesion. The hilum of the liver showed dilated, large intrahepatic bile ducts with wall thickening and increased hilar soft tissue fibrosis.  Intrahepatic calculi were identified. There was also adjacent liver parenchymal atrophy. No mass lesion was identified.

Microscopically, there was bile duct dilation, periductal edema and/or fibrosis, and inflammatory infiltration including neutrophils, lymphocytes, and plasma cells. Bile duct epithelium exhibited patchy regenerative hyperplasia without dysplasia. Focally, prominent periductal lymphoid follicles were noted (Figure 1). Foci of intraductal calculi were also identified (Figure2). There is adjacent liver parenchymal atrophy without cirrhosis. There is no significant ductular reaction.  Gallbladder shows chronic inflammation and prominent reactive lymphoid follicles, consistent with follicular cholecystitis. Immunostains of IgG4 and IgG were performed on one perihilar section and highlighted positive plasma cells without an IgG4 predominance. IgG4/IgG ratio is less than 5%.

This is a case of severe chronic cholangitis. The presence of intrahepatic bile duct ectasia with hepatolithiasis, predominantly affecting left lateral segment and parenchymal atrophy, fits the description of segmental cholangiectasia (i.e., recurrent pyogenic cholangitis ) of the liver.

Segmental cholangiectasia is a recently described rare entity (reference 1) in non-Asian population. Since it shares similar histologic features with classic recurrent pyogenic cholangitis, which is more common in Asian population (reference 2 and 3), the two entities are currently considered as the same diagnostic category. The etiology and pathogenesis of the disease is still speculative. However, recently, a hypothesis centered on the role of E. coli in promoting bile precipitation through its bacterial β-glucuronidase activity has gained popularity. Chronic bacterial infection of the intrahepatic bile ducts can induce inflammation and scarring, eventually leading to stenosis, proximal cholangiectasia, and hepatolithiasis. There appears a propensity to involve the left lateral segment, perhaps due to the sharp angulation of intrahepatic bile ducts from the site causing poor drainage.

To differentiate segmental cholangiectasia/recurrent pyogenic cholangitis from primary sclerosing cholangitis (PSC) can be challenging. Although most PSC involves entire biliary tree without a left segmental propensity, intrahepatic segmental PSC has been reported.  Nonetheless, PSC tends to occur in relatively young patients, often associated with a clinical history of inflammatory bowel disease. Histologically, PSC often presents with fibro-obliterative lesion, ductal loss, marked ductular reaction, chronic cholestasis and eventually biliary cirrhosis.  These are not common findings in cases of segmental cholangiectasia/recurrent pyogenic cholangitis. In fact, lack of exuberant ductular reaction in the adjacent liver parenchyma appears a useful feature to distinguish the two diseases.

Localized Caroli disease is rare but may be confused with segmental cholangiectasia/recurrent pyogenic cholangitis. However, it is a hereditary condition often discovered in young age with renal abnormalities. A family history of cystic kidney disease is a helpful distinction.

There are also many benign conditions presenting as bile duct ectasia with periductal fibrosis, such as ischemic cholangiopathy, IgG4 sclerosing cholangitis, Langerhans cell histiocytosis, etc. In general, their respective characteristic clinical and histologic features are distinct enough not to be confused with segmental cholangiectasia/recurrent pyogenic cholangitis. For example, IgG4 positive plasma cells are significantly increased in IgG4 sclerosing cholangitis while they are rare in segmental cholangiectasia/recurrent pyogenic cholangitis.

Lastly, the clinical presentation and radiographic findings of segmental cholangiectasia/recurrent pyogenic cholangitis are usually alarming for cholangiocarcinoma or intraductal neoplastic process. A careful gross and histologic examination of the resection specimens is always warranted to exclude such possibilities.

References

1. Zhao L, Hosseini M, Wilcox R, Liu Q, Crook T, Taxy JB, Ferrell L, Hart J. Segmental cholangiectasia clinically worrisome for cholangiocarcinoma: comparison with recurrent pyogenic cholangitis. Hum Pathol. 2015 Mar;46(3):426-33. doi: 10.1016/j.humpath.2014.11.019. Epub 2014 Dec 9. PMID: 25600951.
2. Tsui WMS, Lam PWY, Lee W-K, Chan Y-K. Primary hepatolithiasis, recurrent pyogenic cholangitis, and oriental cholangiohepatitis: a tale of 3 countries. Adv Anat Pathol 2011; 18:318-28.
3. Tsui WMS, Chan Y-K, Wong C-T, Lo Y-F, Yeung Y-W, Lee Y-W. Hepatolithiasis and the syndrome of recurrent pyogenic cholangitis: clinical, radiologic, and pathologic features. Semin Liver Dis 2011; 31:33-48.