Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Etiology | Diagrams / tables | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Gonzalez RS. Primary sclerosing cholangitis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/liverpsc.html. Accessed July 15th, 2024.
Definition / general
- Primary sclerosing cholangitis (PSC) is a biliary disease causing progressive stricturing of the biliary tree, leading to cirrhosis and possibly cholangiocarcinoma
Essential features
- Etiology unclear
- Patients are at increased risk of developing ulcerative colitis and cholangiocarcinoma
- Liver biopsy rarely samples the classic "onion skin" periductal fibrosis, meaning typical imaging findings are more reliable for establishing the diagnosis
ICD coding
- ICD-10: K83.01 - primary sclerosing cholangitis
Epidemiology
- Incidence of roughly 1 per 100,000 person years (Hepatology 2011;53:1590)
- Rates may be lower in developing countries, though reliable data are lacking
Sites
- Large intrahepatic and extrahepatic biliary tree affected, including gallbladder (J Hepatol 2008;48:598)
Etiology
- Possibly autoimmune, though etiology uncertain overall
- Gut microbiome has been suggested to play a role (Ann Transl Med 2016;4:512, World J Gastroenterol 2020;26:2768)
- Siblings of primary sclerosing cholangitis patients more likely to develop primary sclerosing cholangitis, suggesting a genetic component (Clin Gastroenterol Hepatol 2008;6:939)
Clinical features
- M:F = 2:1
- Usually age 30 - 50; can occur in children (Hepatology 2017;66:518)
- Half asymptomatic at diagnosis
- Symptoms: fatigue, pruritus, jaundice, right upper quadrant pain / tenderness
- Increased risk for bacterial cholangitis and cholangiocarcinoma (Clin Liver Dis 2016;20:67)
- Up to 70% also have inflammatory bowel disease (particularly ulcerative colitis, although fewer than 10% with ulcerative colitis have primary sclerosing cholangitis) (Gut Liver 2018;12:17)
- Patients may also have an overlap syndrome with autoimmune hepatitis (J Hepatol 2011;54:374)
Diagnosis
- Firm diagnostic criteria do not exist
- British Society of Gastroenterology recently offered extensive PSC diagnosis guidelines (Gut 2019;68:1356)
- Diagnosis generally established by cholestatic lab findings combined with bile duct stricturing on imaging (Lancet 2018;391:2547)
- Liver biopsy useful to rule out other possibilities but generally cannot establish the diagnosis
Laboratory
- Elevated alkaline phosphatase; variable bilirubin
- Many patients are pANCA positive, though this is nonspecific and serology is not helpful in general (World J Gastroenterol 2008;14:3781)
- Usually negative antimitochondrial antibody
Radiology description
- Multifocal bile duct strictures causing a "beads on a string" appearance on magnetic resonance cholangiography and endoscopic retrograde cholangiopancreatography (J Hepatol 2017;66:1265)
- Patients without such imaging findings who otherwise appear to have primary sclerosing cholangitis may have small duct primary sclerosing cholangitis (Gastroenterology 2008;134:975)
Radiology images
Prognostic factors
- Small duct primary sclerosing cholangitis has a better outcome than typical primary sclerosing cholangitis (Gut 2002;51:731)
- Anti-GP2 IgA autoantibodies reportedly indicate poor prognosis (Gut 2017;66:137)
Case reports
- 26 year old man with primary sclerosing cholangitis and ulcerative colitis with low grade dysplasia (J Crohns Colitis 2013;7:e61)
- 33 year old man with primary sclerosing cholangitis and Crohn's disease (Intern Med 2012;51:2077)
- 84 year old woman with primary sclerosing cholangitis and CREST syndrome (J Med Case Rep 2015;9:272)
- 2 patients with overlap between primary sclerosing cholangitis and primary biliary cholangitis (Dig Liver Dis 2015;47:432)
Treatment
- Ursodeoxycholic acid can improve lab values but does not halt disease progression (Lancet Gastroenterol Hepatol 2016;1:68)
- Obeticholic acid also emerging as a treatment (J Hepatol 2020;73:94)
- Only truly effective treatment is liver transplantation, though disease recurs in 33% of patients (Hum Pathol 2003;34:1127)
Gross description
- Alternating fibrosis / stenosis and ectasia of bile ducts, with bile sludge and calculi
- Liver may be distorted or cirrhotic
Microscopic (histologic) description
- Classic finding is "onion skin" fibrosis around affected medium sized bile ducts; smaller ducts rarely affected (except in small duct primary sclerosing cholangitis), meaning biopsy sampling rarely demonstrates this finding
- Progressive atrophy of bile duct epithelium and obliteration of the lumen, leaving a fibrous scar
- Ductular reaction and cholestasis may occur
- Inflammatory infiltrate is typically mild and limited to biliary epithelium and portal tracts, though largest ducts may show increased infiltrate
- Extravasated bile may elicit xanthomatous or granulomatous response
- Portal edema and fibrosis may be seen secondary to obstruction of larger ducts
- Primary sclerosing cholangitis cirrhosis shows the typical biliary jigsaw pattern
- Cholangiocarcinoma may occur in primary sclerosing cholangitis, preceded by intestinal metaplasia and biliary intraepithelial neoplasia (Am J Surg Pathol 2010;34:27)
- Several staging systems exist, with the Ludwig system the most commonly used (Hepatology 2017;65:907):
- Cholangitis / portal hepatitis
- Periportal fibrosis or periportal hepatitis
- Bridging fibrosis or necrosis
- Cirrhosis
Microscopic (histologic) images
Sample pathology report
- Liver, biopsy:
- Liver parenchyma with ductular reaction, bile duct distortion with focal inflammation and minimal portal chronic inflammation (see comment)
- Comment: The reported finding of bile duct stricturing on magnetic resonance cholangiopancreatography is noted. While the histologic findings are not specific, they are compatible with primary sclerosing cholangitis. A trichrome stain shows no significant fibrosis.
Differential diagnosis
- Cholangiocarcinoma:
- May have similar radiologic findings
- Primary biliary cholangitis:
- Florid duct lesions, more prominent inflammation
- Secondary sclerosing cholangitis:
- Due to stones, prior surgery
- "Onion skin" fibrosis and inflammation often more diffuse
- Duct obstruction:
- May occur due to primary sclerosing cholangitis or other causes
- Pure duct obstruction often has early cholestasis
- IgG4 related sclerosing cholangitis:
- More prominent inflammation, with numerous IgG4 positive plasma cells by IHC
- Disease has more aggressive clinical course (shorter time to transplant, higher likelihood of recurrence) (Am J Surg Pathol 2010;34:88, World J Gastroenterol 2013;19:7661)
Additional references
Board review style question #1
Which of the following modalities is most useful for establishing a diagnosis of primary sclerosing cholangitis?
- Liver biopsy
- Liver enzymes
- Magnetic resonance cholangiography
- Serology
Board review style answer #1
Board review style question #2
A 60 year old man presents with signs and symptoms of liver failure. He discloses a long history of abdominal pain and intermittent jaundice but chose not to visit a doctor previously. He is found to have cirrhosis and ultimately undergoes liver transplantation. Histologic examination shows the following
Which of the following is true about this patient?
![](https://www.pathologyoutlines.com/imgau/liverPSCgonzalez10.jpg)
Which of the following is true about this patient?
- He is at increased risk of developing Crohn's disease but not ulcerative colitis
- He appears to have the small duct variant of this disease
- Serologic testing would demonstrate positive antimitochondrial antibodies
- The liver explant should be carefully examined to rule out cholangiocarcinoma
Board review style answer #2
D. The liver explant should be carefully examined to rule out cholangiocarcinoma
Comment Here
Reference: Primary sclerosing cholangitis
Comment Here
Reference: Primary sclerosing cholangitis