li-11-6 PRIMARY SCLEROSING CHOLANGITIS by Dr. E. Orfei
Progressive non-specific chronic inflammation and fibrosis of intrahepatic and extrahepatic bile ducts, of unknown etiology.
Similar changes are produced by the secondary sclerosing cholangitis of known etiology.
At difference with primary biliary cirrhosis which affects small intrahepatic bile ducts, namely, interlobular and septal ducts, this disease affects bile ducts of all sizes not necessarily at the same time, indeed it can be confined to only intrahepatic ducts (Small duct disease) or only to large hepatic and extrahepatic ducts (Large duct disease) or it may involve large and small ducts simultaneously (Global disease). Also the gall bladder may involved in the in this inflammatory and fibrotic process.
First recognized by Delbet in France in 1924 and described as "Irregular Fibrosis and Stenosis of the Biliary Tree", to be distinguished from Secondary Sclerosing Cholangitis.
The clinical course is highly variable. In symptomatic cases the disease is progressive and cause biliary cirrhosis with deeply green livers.Cholangitis and Colangioarcinoma are often present.
Probably asymptomatic cases in this disease are more frequent than it is suspected.
The first symptoms are similar to those of PBC: progressive fatigue, pruritus and jaundice in repeated episodes. The onset is therefore insidious and the disorder is usually diagnosed 1-2 years after onset of symptoms. The full picture of cholangitis, pain, fever and jaundice, is rare. most patients present hepatosplenomegaly or jaundice.
Sex: Prevalent in man (75% of cases).
Age: 2-75 years. Pick 25-45 years.
Associated diseases: Inflammatory bowel disease, thyroiditis, pancreatitis, arthritis, celiac sprue, sarcoidosis. Up to85% of patients with PSC have inflammatory bowel disease, especially chronic ulcerative cholitis. Crohn's disease is rarely associated. An individual with inflammatory bowel disease and high serum alkaline phosphstase most likely has PSC. Symptomatic patients may live up to 15 years. Long term life is unlikely even for asymptomatic cases.
Increased serum alkaline phosphatase, transaminase, bilirubin and IgM. Mitochondrial antibodies: rarely present.
Cholangiography: Alternating strictures and dilatations and beading of intra and extraheptic bile ducts. In cholelithiasis the ducts are dilated but not stenosed and beaded.
The cause of PSC is unknown. Most likely the cause is a disorder of the immune system. Specific immunologic markers such as antimitochondrial and anti smooth muscle antibodies
are largely absent. Frequent, however, is the association of PAC with HLA-B8 and HLA-DR3 aplotypes.The lymphocytes that are involved in the inflammatory exudate in affected bile ducts are T-lymphocytes. These immunologic alterations may have a familial distribution.
The pathologic picture is that of a fibrosing obliterative cholangitis but the histological findings are not specific for PSC.
There is thick concentric clean fibrosis around bile ducts with degeneration of bile duct epithelium and transformation of bile ducts into fibrous cords.These fibrous changes are seen in 40% of cases. Rarely the fibrosis affect only intrahepatic bile ducts.
In large ducts, such as extrahepatic and primary intrahepatic ducts, the fibrosis is so thick with young plump fibroblasts replacing the disappeared ducts as to simulate a fibrosarcoma or a Clatchkin tumor. In interlobular and septal ducts the fibrosis is wide and clean of inflammatory cells. Instead of fibrous changes some portal areas show inflammation and disappearance of bile ducts. The inflammation consists of lymphocytes, plasma cells, neutrophils and periductal edema. The typical florid duct lesion that is seen in PBC is not seen in PSC. Periportal cholestasis and granulomas may be present. These finding demonstrate that the distinction between PSC of small ducts and PBC is morphologically possible only in 28% of cases.
The liver biopsy especially in early cases is not distinctive, therefore when the disease is suspected endoscopic retrograde cholangiography must be done. The positivity of this test with negative Anti-Mitochondrial Antibibodies will establish the diagnosis.
Fig.11-6-1. Large ducts fibrosis. This section is from the hilus of the liver deeply green, cholestatic, in a 32 year old male who had PSC of extra and intrahepatic bile ducts. He died within 2 years of acute cholangitis following surgery.
Sections of the white cords in this specimen were diagnosed fibrosarcoma by very renowned pathologists.
Fig. 11-6-2. Septal duct .
This is a septal duct in the previous case. Notice marked periductal fibrosis. Normally septal ducts have a fibrotic cuff.
In this case the fibrosis is excessive.
Fi11-6-3. Small duct fibrosis fibrosis.
In this case notice the portal , periportal and bridging fibrosis
originating from periductal fibrosis. Cirrhosis in this disease and in biliary obstruction in general develops very slowly over a long period of time. These livers will be large and green.
Fig. 11-6-4. Portal duct fibrosis. This is a portal field with a typical PSC obtained by liver biopsy. The cholangiography confirm the diagnosis.
Fig. 11-6-5. Portal bile duct.
High power of previous picture.
Notice the rather clean periductal fibrosis. Although very clear , this change is not specific for PSC, which must be confirmed by cholangiography.
Fig. 11-6-6. Portal inflammation. Unusually PSC
may cause chronic portal inflammation Characterized by disappearance of portal bile ducts.
Fig.11-6-7. Cholangiogram in PSC. Stenoses, dilatations and beading of intrhepatic ducts are the diagnostic features in a case of clinically and morphologically suspected for PSC.
Fig. 11-6-8. Normal Xray
of intrahepatic bile duct branches.
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