Primary sclerosing cholangitis (PSC)

by Stephanie Reid, MD FRCPC
May 19, 2022

What is primary sclerosing cholangitis?

Primary sclerosing cholangitis (PSC) is an autoimmune disease that damages the bile ducts inside and outside the liver. The damage is caused by immune cells that attack the bile duct cells and prevent them from working normally.

PSC is frequently associated with a condition called inflammatory bowel disease (particularly ulcerative colitis). PSC occurs most commonly in young and middle-aged men. Most patients have no symptoms when diagnosed but blood work may reveal elevated levels in a blood test called alkaline phosphatase in over 90% of patients. Other nonspecific symptoms that can occur include fatigue, itchy skin, abdominal pain, yellow skin, and weight loss.

What are the long-term complications of primary sclerosing cholangitis?

There are several complications associated with long-term PSC. The most common complication is a liver disease called cirrhosis, which usually occurs 10-15 years after the diagnosis of PSC. When this occurs, patients may require a liver transplant. PSC also increases the risk of cholangiocarcinoma, a type of bile duct cancer.

What tests are performed to look for primary sclerosing cholangitis

If your doctor suspects that you have PSC, they may order a radiologic test called a magnetic resonance cholangiopancreatography (MRCP) or cholangiography. Classic findings of PSC in these tests include bile ducts that have a beaded appearance caused by multiple areas of narrowing.

How do pathologists make the diagnosis of primary sclerosing cholangitis?

A liver biopsy is performed in primary sclerosing cholangitis mainly to determine the number of ducts that have disappeared due to damage, and also the amount of scarring (fibrosis) within the liver. The diagnosis of PSC is based on your pathologist seeing specific microscopic features including bile duct damage, bile duct loss, concentric fibrosis, cholestasis, and fibrosis. These features are described in greater detail in the sections below.

Microscopic features associated with primary sclerosing cholangitis

Bile duct damage

The liver produces a substance called bile which is used to remove toxins from the body and digest food. The bile produced in the liver drains through channels called bile ducts into the small bowel. Each portal tract contains one bile duct. Your pathologist will look for bile duct damage or active inflammation around the bile ducts.

Bile duct loss

If damage or inflammation continues for a prolonged period of time, bile ducts may be scarred and lost. This will result in portal tracts that only have blood vessels. Your pathologist may record the amount of bile duct loss in multiple ways including stating the actual number lost, the percentage lost, or the degree of loss (mild, moderate, or severe). Some pathologists use the word ductopenia to describe a decreased number of bile ducts.

Concentric fibrosis

Concentric fibrous describes a type of reaction where fibrous cells surround the bile ducts and cause an injury that looks like an “onion skin” when viewed through a microscope. While this type of injury is not seen in all biopsies when found it is highly supportive of the diagnosis of PSC.

Cholestasis

Cholestasis is a word pathologists use to describe bile trapped in the liver. Trapped bile is important because it can cause liver injury. If cholestasis is seen, your pathologist will describe its location within the liver and the amount of trapped bile will be described as mild, moderate, or severe. Because primary sclerosing cholangitis damages the bile ducts, there is often cholestasis present in the liver biopsy.

Fibrosis

Fibrosis is a type of scar tissue that forms in the liver after damage. Because PSC damages the liver, there is a risk of developing fibrosis.  Most pathology reports comment on the amount of fibrosis and will give it a ‘stage’. The stage is dependent on multiple factors including the extent of initial injury, the length of time injury was occurring, and which parts of the liver were damaged. Too much fibrosis disrupts the architecture of the liver and prevents it from functioning properly.

There are several different classification systems used to stage fibrosis but all of them include the type and amount of fibrosis seen. Cirrhosis is the last stage of fibrosis and it is characterized by large fibrous bands in the liver. In diseases that affect the bile ducts (such as PSC), the fibrosis may be patchy and irregular.  It prevents the liver from carrying out its normal functions and may lead to a medical condition called ‘liver failure’.

Other features that may be described in your report for primary sclerosing cholangitis

Adequacy

The liver is divided into ‘zones’ and at the center of each zone is a structure called a ‘portal tract’. Portal tracts are important because they contain blood vessels and channels that move other substances such as bile in and out of the liver.

When examining a liver biopsy, your pathologist must first determine if the sample contains the minimum amount of portal tracts required to make an accurate diagnosis. The adequacy of the biopsy may be reported simply as “yes” or “no”, or the number of portal tracts seen may be stated.

Fragmentation

The condition of the liver biopsy when viewed under the microscope is usually described. If the liver biopsy is brittle and has broken apart this will be described, as it may be a clue to specific liver conditions.

Steatosis

Steatosis is the term used to describe the presence of fat droplets within the hepatocytes. In steatosis, the hepatocytes contain clear areas of fat droplets when viewed under a microscope. Pathologists use a scale to describe the amount of fat in a liver with steatosis. The scale is based on the percentage of liver cells that contain fat droplets:

The scale used by most pathologists includes:

• Mild – Fat droplets are seen within less than  33% of the hepatocytes in the biopsy
• Moderate – Fat droplets are seen within 33 – 66 % of hepatocytes in the biopsy
• Severe – Fat droplets are seen within greater than 66 % of hepatocytes in the biopsy.

Ballooning hepatocytes

Ballooning hepatocytes are liver cells that are damaged or dying. The hepatocyte swells to several times its normal size and becomes clear in areas. Ballooning hepatocytes are required for the diagnosis of several medical liver diseases. The amount of hepatocyte ballooning present is reported as mild, moderate, or severe.

Mallory bodies

Mallory bodies form because of damage to hepatocytes. Under the microscope, they look like dark pink material inside the hepatocytes cells. Mallory bodies are present in specific forms of liver disease and their presence or absence helps guide pathologists to a diagnosis.

Iron

Iron can build up within the liver as a result of the abnormal breakdown of iron, increased iron in the body (such as after multiple blood transfusions), or when the liver is not functioning properly (as in liver cirrhosis). This excess iron can be seen within the hepatocytes or within immune cells called macrophages. If iron is present in your tissue, your pathologist will report its location and severity.