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Primary Sclerosing Cholangitis

Definition

Disorder of the biliary tract in which there is inflammation and sclerosis of usually the medium and large ducts. About 6% of cases have small duct involvement only. Associated with inflammatory bowel disease.

Clinical Features

  • One of most common adult chronic cholestatic liver diseases
  • 75% cases are male
  • Average age at diagnosis 40 years:
    • sometimes children1
  • Typically associated with inflammatory bowel disease (70%)2–4

Histopathology

Portal Tracts

  • Proximal to strictures:
    • only features of obstruction and cholangitis
  • Affected by primary disease:
  • Key lesion:
    • onion skin-type periductal fibrosis (Fig. 1
      Primary sclerosing cholangitis. Detail of portal tract with moderately dense inflammatory infiltrate (mainly lymphocytes, some eosinophils) and concentric, lamellated, periductal fibrosis (‘onion skin’ fibrosis) around the interlobular bile duct (center). (H&E)

      Fig. 1: Primary sclerosing cholangitis. Detail of portal tract with moderately dense inflammatory infiltrate (mainly lymphocytes, some eosinophils) and concentric, lamellated, periductal fibrosis (‘onion skin’ fibrosis) around the interlobular bile duct (center). (H&E)

      ):
      • with degeneration and atrophy of epithelial lining:
        • results in disappearance of duct and eventual replacement by a fibrous scar
          • loss of ducts more frequent in smaller portal tracts
          • sometimes scars unusually prominent and resemble keloid scars6,7
        • in <40% of biopsy specimens5
        • more often medium-sized tracts8
        • not pathognomonic – also in other types of biliary disease
        • not present in every stage of disease
  • If longlasting and more severe disease:
    • portal fibrosis more marked
    • fibrous septa
    • biliary cirrhosis
  • More progressive disease:
    • moderate to severe lymphocytic type of interface hepatitis9
  • Less severe disease:
    • only mild and insignificant lesions over several years10
  • Increased risk of developing cholangiocarcinoma:11
    • strong association with dysplasia of bile duct epithelium12

Parenchymal Changes

  • Less striking than portal changes
  • Correspond to features of chronic cholestasis
  • May be nodular regenerative hyperplasia before precirrhotic stage

Special Stains and Immunohistochemistry

  • PAS–diastase staining:
    • thickening of basement membrane around damaged ducts (Fig. 2
      Primary sclerosing cholangitis. Overview of portal tract and periportal parenchyma. This portal tract shows only mild inflammation; two interlobular bile ducts show clear-cut thickening of their basement membrane, a helpful diagnostic feature. (PAS–diastase stain)

      Fig. 2: Primary sclerosing cholangitis. Overview of portal tract and periportal parenchyma. This portal tract shows only mild inflammation; two interlobular bile ducts show clear-cut thickening of their basement membrane, a helpful diagnostic feature. (PAS–diastase stain)

      ), or
    • wrinkled empty basement membranes13

Diagnosis

  • Usually combined large and small duct PSC
  • Small duct PSC corresponds to involvement of only microscopically identifiable (septal and interlobular) ducts:
    • previously indicated by now obsolete term pericholangitis14

Other investigations

  • Cholangiography

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Primary Sclerosing Cholangitis

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  • Chronic hepatitis:
    • lacks:
      • periductal fibrosis
      • ductopenia
      • cholestatic features.
  • PBC:
    • may be difficult to differentiate in later stages
    • epithelioid granulomas:
      • also in about 4% of PSC cases, but not as part of granulomatous cholangitis15
    • florid portal inflammation with or without lymph follicle formation favors PBC
  • Overlap autoimmune hepatitis and PSC described16–18
  • Other vanishing bile duct diseases

References

1 Roberts EA. Primary sclerosing cholangitis in children. J Gastroenterol Heptol. 1999;14:588–593.

2 Angula P, Lindor KD. Primary sclerosing cholangitis. Hepatology. 1999;30:325–332.

3 Harnois D, Lindor KD. Primary sclerosing cholangitis: evolving concepts in diagnosis and treatment. Dig Dis. 1997;15:23–41.

4 Martins EB, Chapman RW. Sclerosing cholangitis. Curr Opin Gastroenterol. 1999;15:436–441.

5 Hawkins EP, Jordan GL, McGavran MH. Primary leiomyoma of the liver. Successful treatment by lobectomy and presentation of criteria for diagnosis. Am J Surg Pathol. 1980;4:301–304.

6 Bhathal PS, Powell LW. Primary intrahepatic obliterating cholangitis: a possible variant of sclerosing cholangitis. Gut. 1969;10:886–893.

7 MacSween RNM, Burt AD, Haboubi NY. Unusual variant of primary sclerosing cholangitis. J Clin Pathol. 1987;40:541–545.

8 Harrison RF, Hubscher SG. The spectrum of bile duct lesions in end-stage primary sclerosing cholangitis. Histopathology. 1991;19:321–327.

9 Aadland E, Schrumpf E, Fausa O, Elgjo K, Heilo A, Aakhus T, et al. Primary sclerosing cholangitis: a long-term follow-up study. Scand J Gastroenterol. 1987;22:655–664.

10 Broome U, Glaumann H, Hultcrantz R. Liver histology and follow up of 68 patients with ulcerative colitis and normal liver function tests. Gut. 1990;31:468–472.

11 Broomé U, Olsson R, Lööf L, Bodemar G, Hultcrantz R, Danielsson A, et al. Natural history and prognostic factors in 305 Swedish patients with primary sclerosing cholangitis. Gut. 1996;38:610–615.

12 Fleming KA, Boberg KM, Glaumann H, Berrgquist A, Smith D, Clausen OPF. Biliary dysplasia as a marker of cholangiocarcinoma in primary sclerosing cholangitis. J Hepatol. 2001;34:360–365.

13 Fleming KA. Interlobular bile duct basement membrane thickening – a specific marker for primary sclerosing cholangitis (PSC)?. J Pathol. 1993;169 (Suppl):135A.

14 Ludwig J. Small-duct primary sclerosing cholangitis. Semin Liver Dis. 1991;11:11–17.

15 Ludwig J, Colina F, Poterucha JJ. Granulomas in primary sclerosing cholangitis. Liver. 1995;15:307–312.

16 Domschke W, Klein R, Terracciano L-M, Jung P, Kirchner T, Berg PA, et al. Sequential occurrence of primary sclerosing cholangitis and autoimmune hepatitis type III in a patient with ulcerative colitis: a follow up study over 14 years. Liver. 2000;20:340–345.

17 Kaya M, Angulo P, Lindor KD. Overlap of autoimmune hepatitis and primary sclerosing cholangitis: an evaluation of a modified scoring system. J Hepatol. 2000;33:537–542.

18 McNair AN, Moloney M, Portmann BC, Williams R, McFarlane IG. Autoimmune hepatitis overlapping with primary sclerosing cholangitis in five cases. Am J Gastroenterol. 1998;93:777–784.

Last updated: 23 Nov 2006

Primary Sclerosing Cholangitis

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