Ref: Robbins Pathologic Basis of Disease, 8th editionExplanation:PRIMARY SCLEROSING CHOLANGITIS (PSC). Anti smooth muscle antibodies, and RA are present in a minority of patients.Symptoms at presentation include progressive fatigue, pruritus, jaundice and elevation of serum alkaline phosphatase.Severely afflicted persons show' symptoms associated with chronic liver disease, including weight loss, ascites, variceal bleeding, and encephalopathy.Cholangiocarcinoma may develop in 10% to 15% of individuals, with a median time of 5 years from diagnosis.There is It is a chronic cholestatic disorder, characterized by progressive fibrosis and destruction of extrahepatic and large intrahepatic bile ducts.Since changes in the ducts are patchy, retrograde cholangiography shows a characteristic "heading" of the contrast medium in the affected segments.The large bile ducts show periductal fibrosis that obliterates the lumen, leaving a solid cord scar with few inflammatory cells.Associated with inflammatory bowel disease, esp chronic ulcerative colitis 7(1% casesPrevalence of PSC in persons with ulcerative colitis is about 4%.Occurs in the third through fifth decades, most often after development of inflammatory bowel disease.Males are affected more often than females in a ratio of 2 : 1.Pathogenesis and Clinical CourseThe cause of primary sclerosing cholangitis is unknown.Atypical pANCA is present in 80% of cases ( Atypical because, though they showr perinuclear pattern, the antibody is targeted against 'Nuclear envelope protein' instead of myeloperoxidase)Anlimitochondrial antibodiesno effective therapy for PSC, except for liver transplantation.MorphologyThe characteristic feature of PSC is a fibrosing cholangitis of bile ducts.Affected portal tracts show concentric periductal onion-skin fibrosis and a modest lymphocytic infiltrate.Progressive atrophy of the bile duct epithelium leads to obi iteration of the lumen, leaving behind a solid, cordlike fibrous scar.As the disease progresses, the entire liver becomes markedly cholestatic and fibrotic leading on to development of biliary cirrhosis.