Primary biliary cholangitis
|Primary biliary cholangitis|
|Diagnosis in short|
Primary biliary cholangitis. H&E stain.
|Synonyms||primary biliary cirrhosis (obsolete term)|
|LM||"florid duct lesion": intraepithelial lymphocytes - in bile duct, bile duct epithelial cells with eosinophilic cytoplasm; plasma cells; +/-granulomas (close to bile duct); +/-"garland" cirrhosis -- has irregular border|
|LM DDx||sarcoidosis, primary sclerosing cholangitis, viral hepatitis, autoimmune hepatitis, drug-induced liver disease, Hodgkin's lymphoma|
|Site||liver - see medical liver diseases|
|Associated Dx||other autoimmune conditions, e.g. celiac disease, Sjögren syndrome|
|Clinical history||woman, middle age|
|Blood work||AMA +ve|
Primary biliary cholangitis, abbreviated PBC, is a rare medical liver disease.
It was previously known as primary ciliary cirrhosis.
- Female>male (~9:1).
- Usually middle age.
- Associated with other autoimmune conditions (Sjögren syndrome, progressive systemic sclerosis, celiac disease).
- AMA +ve.
- Septal bile duct attacked.
- Ursodeoxycholic acid.
- May be indication for transplant.
- "Florid duct lesion":
- Intraepithelial lymphocytes - in bile duct - key feature.
- Bile duct epithelial cells with eosinophilic cytoplasm.
- Plasma cells.
- Granulomas - close to bile duct.
- Seen in classic presentation -- often not present or poorly formed.
- Focal damage (may be missed on biopsy -- due to sampling).
- "Garland" cirrhosis -- has irregular border (unlike in EtOH).
- Garland originally "wreath of flowers" (in French).
- PAS stain useful for examining basement membrane... which is lost in PBC.
- Lobular inflammation should be minimal.
- May cause cholestatic picture.
- Sarcoidosis (if granulomas present).
- Primary sclerosing cholangitis.
- Viral hepatitis.
- Autoimmune hepatitis.
- Drug-induced liver disease.
- Hodgkin's lymphoma.
Primary biliary cirrhosis. Inflamed triads [arrows] amid undisturbed hepatocytes (Row 1 Left 40X). Granuloma in portal triad (Row 1 Right 400X). Florid duct lesion (Row 2 Left 400X). Triad missing interlobular bile duct (Row 2 Right 400X).
Primary biliary cirrhosis. AMA positive. Viral serology/ANA negative. No definite granulomas. Ill defined triads, inflamed lobule (Row 1 Left 40X). Triad without a bile duct. Macrophages & occasional lymphocytes without epithelioid cells needed for granuloma and space where bile duct likely once was [cyan arrowhead] (Row 1 Right 400X). PAS without diastase shows triad lacking bile duct and piecemeal necrosis (Row 2 Left 200X). PAS with diastase shows bile duct/proliferating bile ductules with epithelial injury and hepatocytes with ballooning degeneration (Row 2 Right 400X). Trichrome shows space of Disse collagenization and periportal fibrosis without definite bridging (Row 3 Left 100X). Iron stain shows isolated focus of hepatocytes with cytoplasmic blue granules (Row 3 Right 200X).
Primary biliary cirrhosis. Two inflamed triads accompany acini with mild steatosis (Row 1 Left 20X). A triad bears a poorly formed granuloma [yellow arrowhead]. A bile duct is also seen [red arrowhead] (Row 1 Right 200X). A triad lacks a bile duct (Row 2 Left 200X). Trichrome of the same triad shows portal fibrosis (Row 2 Right 200X).
Primary biliary cirrhosis with bridging fibrosis. Acini & lobules distorted by inflammation (Row 1 Left 40X) Loose granuloma in triad without duct (Row 1 Right 200X) Well-formed granuloma (Row 2 Left 200X) Piecemeal necrosis, PAS without diastase (Row 2 Right 200X) Damaged bile duct, PAS with diastase (Row 3 Left 400X) Bridging fibrosis, trichrome (Row 3 Right,200X)
Primary biliary cirrhosis with Metavir stage 4 fibrosis (extensive fibrosis/cirrhosis). The patient was AMA positive and ANA negative. A. Inflamed tracts and bridges are intensely inflamed, with odd appearing edges of hepatocytes (arrows), suggestive of a jig saw pattern [40x]. B. Trichrome shows thin fibrous bands bounding regenerative isles (arrows) [Trichrome, 100X]. C. Reticulin shows two cell thick cords and cords lacking orientation, documenting regeneration; black lines about single cells document piecemeal necrosis [100X]. D. Lymphocytes, plasma cells, and macrophages, show piecemeal necrosis, surrounding hepatocytes (cyan arrows), as well as spreading into the lobule (green arrows), with aggregates reflecting spotty necrosis (black arrow). [400X]. E. PAS with diastase highlights a proliferated bile ductule (arrows) with epithelial damage [400X]. F. PAS with diastase shows an arteriole (green arrow) at great distance from an isolated bile ductule at the periphery of the triad (cyan arrow), consistent with loss of bile duct; neutrophils (black arrows) do not prove ascending cholangitis [400X].
PBC is staged according to Ludwig:
- Stage 1: Portal - inflammation or bile duct abnormalities.
- Stage 2: Periportal - periportal fibrosis (enlargement of portal tracts) +/- inflammation.
- Stage 3: Septal - septal fibrosis +/-inflammation in septa.
- Stage 4: Cirrhosis - nodules of hepatocytes +/- inflammation.
- There can be significant variation in staging on biopsy - due to variability of fibrosis in a PBC liver.
- "Worst area" in biopsy specimen is used to determine stage.
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