Pathology Pearls Post 7: Primary Biliary Cholangitis

Phoenix Bell

Brief Case Presentation

A 42-year-old female with a past medical history of hypothyroidism presents with 6-month history of right upper quadrant pain, fatigue, and joint pain. Results from her liver function tests and serologic studies are seen below:

Lab Value Results

Lab Value Result
AST 90 U/L (10-50 U/L)
ALT 115 U/L (10-50 U/L)
ALP 125 U/L (35-130 U/L)
Total Bilirubin 0.2 mg/dL (0.0-1.0 mg/dL)
HAV Negative
HBV Negative
HCV Negative
ANA Negative
dsDNA Ab Negative
Mitochondrial M2 Ab
Positive
Smooth Muscle Ab Positive
IgG 1425 mg/dL

Liver Biopsy

At low power, there is increased inflammation centered within the portal tracts, while the lobules show no increase in activity (Figure 1). Medium power reveals that the inflammation surrounds the usual portal tract structures, including branches of the portal vein, hepatic artery, and bile ducts (Figure 2).

Figure 1. Low power shows the liver biopsy has portal-based inflammation.
Figure 2. Medium power reveals the presence of the portal vein, hepatic artery, and bile ducts, surrounded by an inflammatory infiltrate.

Higher power shows that the inflammation is predominantly mononuclear, composed of lymphocytes, histiocytes and plasma cells with scattered eosinophils (Figure 3).

Figure 3. Higher power shows the inflammation is composed of lymphocytes, histiocytes, and plasma cells.

Bile duct injury in the form of intraepithelial lymphocytes and cytoplasmic vacuolation is seen (Figure 4). No interface activity is identified.

Figure 4. Bile duct injury is present, seen as intraepithelial lymphocytes.

Trichrome (Figure 5) and reticulin (Figure 6) stains show no increased fibrosis.

Figure 5. Trichrome stain showing no significant increase in fibrosis.
Figure 6. A reticulin stain reveals a normal degree of fibrosis within the portal tracts.

The histologic findings are consistent with primary biliary cholangitis (PBC).

Histologic Features of PBC

PBC is characterized by portal-based inflammation and bile-duct injury. Inflammation within the portal tracts is composed of lymphocytes, histiocytes, plasma cells, and eosinophils and occasionally neutrophils. Bile duct injury may be seen as increased intraepithelial lymphocytes (lymphocytic cholangitis/ductitis), nuclear pleomorphism, and cytoplasmic vacuolation. In approximately half of PBC cases, bile duct injury may be associated with a granulomatous response, which is known as a "florid duct lesion". In more severe cases of PBC, interface activity and ductopenia (bile duct loss) may be seen.  In PBC, bile ducts disappear without trace and are not associated with a fibrous scar (in contrast to PSC, which will be discussed in the next post). In general, there is no or minimal lobular inflammation.

Differential Diagnosis for PBC

The main histologic differential diagnosis for PBC includes primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), drug/medication-induced injury (DILI), and hepatitis C infection. In cases with a granulomatous response, sarcoidosis may also be considered.

The characteristic histologic findings in PSC often affect larger ducts and include "onion-skin fibrosis", in which the bile ducts are surrounded by concentric fibrosis. In more progressed cases, a fibro-obliterative duct lesion may be seen, in which the bile duct has been replaced by a scar. A needle biopsy of liver parenchyma often shows nonspecific findings of extrahepatic biliary obstruction.  In contrast to PBC, PSC shows more bile ductular proliferation and plasma cells are less prominent.

Like PBC, AIH shows mild to moderate inflammation in the portal tracts, often rich in plasma cells (see LFN Post 6). In contrast to PBC, AIH will demonstrate increased interface and lobular activity and lacks bile duct injury. Further, AIH is less likely to have AMA positivity.

DILI has many patterns of injury including hepatitic, cholestatic, granulomatous, steatohepatitic, and cholangitic etc. The ductopenic pattern of DILI can mimic PBC as it shows duct injury/ductopenia and portal inflammation; however, this type of injury also tends to show more bile duct injury and cholestasis. Clinical correlation, particularly the timeline of onset of injury with medication use, as well as serologic studies, are important to delineate the injury as DILI or PBC.

Lastly, although much less commonly encountered today, HCV infection can mimic PBC. HCV manifests itself as portal-based lymphocytic inflammation (which may show mild bile duct injury). In contrast to PBC, HCV more often demonstrates increased interface activity and shows minimal lobular activity. Correlation with viral serology is necessary.

References

  1. R. Saxena, Practical Hepatic Pathology: A Diagnostic Approach: Second Edition. 2017.
  2. Torbenson, Atlas of Liver Pathology: A Pattern-Based Approach. 2020.
  3. Odze and Goldblum, Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas: Third Edition. 2014.

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