Biliary Ductal Dilation: Just Another Case of Malignancy?


A 47-year-old male presents with painless jaundice.  He also reports decreased appetite and energy, along with diffuse itching, pale stools, and dark urine. He denies any weight loss or history of liver disease. His physical exam is notable for jaundice and his labs show cholestasis (total bilirubin 6.3, primarily conjugated, and alkaline phosphatase of 347) and elevated transaminases (AST 160 and ALT 547). A MRCP shows intra-hepatic biliary dilation and retroperitoneal fibrosis without a mass or filling defect

What is the most likely underlying diagnosis?

Correct Answer:

IgG4 cholangiopathy

The most likely diagnosis for this patient is IgG4 cholangiopathy. While his symptoms and jaundice point to a hepatobiliary disease, his liver chemistries are ultimately non-specific. The MRCP is important for further assessment as it ruled out cholangiocarcinoma and choledocholithiasis. Primary sclerosing cholangitis (PSC) is less likely in a patient without inflammatory bowel disease, although it can be seen. With retroperitoneal fibrosis found on imaging, IgG4 cholangiopathy is much more likely. Ultimately, the patient underwent ERCP and cytology brushings were positive for IgG4 cells, confirming the diagnosis of IgG4 cholangiopathy. Read on to learn more about the presentation, diagnosis, and management of this rare disease.

Epidemiology and Presentation of IgG4 Cholangiopathy

IgG4 cholangiopathy is an autoimmune disorder that manifests as inflammation of the bile ducts, which can progress to ductopenia, cirrhosis, and bile duct cancer. This disease is often accompanied by IgG4 related diseases affecting other organs, including the lacrimal and salivary glands and most commonly the pancreas. Unlike many other autoimmune disorders, there is a male predominance, with a 3.3:1 male to female ratio. The age at diagnosis varies, between 14-85, however the average age at diagnosis is 69.

The presentation of IgG4 cholangiopathy is highly variable. The most common presenting sign is jaundice, with an estimated 77% of patients developing it prior to evaluation. Other common symptoms include weight loss and abdominal pain, and new onset diabetes has also been reported. IgG4 cholangiopathy should always be considered as a possible diagnosis when evaluating a patient for primary sclerosing cholangitis (PSC), although it has been reported that approximately 9% of patients with PSC have high serum IgG4 levels in the absence of IgG4 cholangiopathy. Important clinical distinctions between IgG4 cholangiopathy and PSC are noted in Table 1.

Table 1 - Clinical distinctions between IgG4 cholangiopathy and primary sclerosing cholangitis

Current Concepts in Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis. Clin Transl Gastroenterol 2015. IAC is another term for IgG4 cholangiopathy.

Back to the case

The patient was admitted to the hospital for further evaluation. He had normal tumor markers, including CA 19-9, and a negative serologic workup for chronic liver disease. IgG levels were also normal. He underwent EUS and ERCP with cholangioscopy, which showed a 2cm x 1cm hilar mass; brushings, biopsies, and FISH were performed which did not reveal malignancy, and bilateral biliary stents were ultimately placed. His symptoms improved after stenting. Special staining of the biopsies revealed an elevated amount of IgG4 cells.

Diagnosis of IgG4 Cholangiopathy

Making a diagnosis of IgG4 cholangiopathy is challenging. Contrary to the name of this condition, approximately 10% of patients with IgG4 cholangiopathy do not have elevated levels of serum IgG4. The Japan Biliary Association has proposed standardized diagnostic criteria for IgG4 cholangiopathy as shown in Figure 1.

Figure 1 - Proposed diagnostic criteria by the Japan Biliary Association

Taken from: Clinical Diagnostic Criteria of IgG4-related Sclerosing Cholangitis. J Hepatobiliary Pancreat Sci 2012

A definitive diagnosis is made with options 1 and 3; 1, 2, and 4 (a and b); 4 (a, b, and c); and 4 (a, b, and d).

Figure 2 - Example of obliterative phlebitis (destruction of small veins due to lymphoplasmacytic infiltration and ultimately fibrosis) on histopathology

Taken from: Clinical Practice Guidelines for IgG4-related sclerosing cholangitis. J Hepatobiliary Pancreat Sci 2019

Treatment for IgG4 Cholangiopathy

The mainstay of treatment for IgG4 cholangiopathy is steroids. Guidelines recommend initiating prednisolone at 0.6mg/kg/day for induction, with a goal to reduce the dose of prednisolone to 5mg/day within three months. This dose should be maintained for a minimum of three years, with serial clinical, laboratory, and radiologic monitoring.

Figure 3- Guidelines for treating IgG4 cholangiopathy

Taken from: Clinical Diagnostic Criteria of IgG4-related Sclerosing Cholangitis. J Hepatobiliary Pancreat Sci 2012

Back to the case

The patient was started on prednisolone dosed according to his weight. His liver enzymes normalized within two weeks and repeat imaging at one month showed resolution of his biliary dilation and improvement in the extent of his retroperitoneal fibrosis.