Title : LiverObjectives : to1. Describe α1- Anti trypsin deficiency disorder.2. Explain intrahepatic biliary tract diseases.3. Identify benign tumors of liver.4. Study malignant tumors of liver.5. Out line metastatic tumors to liver.
α1-ANTITRYPSIN DEFICIENCY : Autosomal-recessive disorder. Low serum levels of protease inhibitor(α1-antitrypsin). Leads to pulmonary emphysema and liver diseases. Gene which located on chromosome 14is very polymorphic (75 forms identified). Most common genotype is PiMM ( 90% of individuals). Most common mutation (homozygotes PiZZ) withcirculating α1-antitrypsin level only 10% of normal.
Morphology:round-to-oval cytoplasmic inclusionsin hepatocytes which are acidophilic inH &E stains, and strongly PAS-positive.Clinical Features:• Neonatal hepatitis with cholestatic jaundice .• In adolescence: hepatitis or cirrhosis.• Disease may remain silent until cirrhosis appearsin middle to later life.• Hepatocellular carcinoma in 2% to 3% of PiZZ adults,usually in setting of cirrhosis.
Intrahepatic Biliary Tract DiseaseSecondary Biliary Cirrhosis :Etiology: Extrahepatic bile duct obstruction by:-• biliary atresia.• Gallstones.• Stricture.• carcinoma of pancreatic head.Sex predilection: None.Symptoms and signs:Pruritus, jaundice, malaise, dark urine, light stools ,and hepatosplenomegaly.
Lab. findings:• Conjugated hyperbilirubinemia.• increased serum level of : alkaline phosphatase,bile acids, and cholesterol.Morpholgy:• Prominent bile stasis in bile ducts.• bile ductular proliferation with surrounding neutrophils.• portal tract edema.Secondary biliary cirrhosis ischaracterized by regenerationnodules, surrounded byfibrous septa. biliary ducts( proliferated or distended ).
Primary Biliary Cirrhosis:Etiology: autoimmune, 90% of patients havecirculating antimitochrondrial antibodies .Sex predilection: Female to male: 6:1Symptoms and signs: Same assecondary biliary cirrhosis ; insidious onset.Lab. findings: Same as secondary biliary cirrhosis,plus elevated serum IgM autoantibodies( M2 form of antimitochondrial antibody-AMA).Morphology:• Dense lymphocytic infiltrate in portal tracts.• granulomatous destruction of bile ducts.
PRIMARY BILIARY CIRRHOSIS: This imageshows dense lymphoid infiltrate in a portaltract . This stage is also known as “floridduct lesion”Liver, primary biliary cirrhosis:non-necrotizing granuloma
Primary Sclerosing Cholangitis:Etiology: Unknown, possibly autoimmune;50–70% have inflammatory bowel disease.Sex predilection: Female to male: 1:2Symptoms and signs: Same assecondary biliary cirrhosis; insidious onset.Lab. findings: Same as secondary biliary cirrhosis,plus elevated serum IgM.Morphology : concentric Periductal portaltract fibrosis(onion-skin fibrosis) segmental stenosis ofextrahepatic and intrahepaticbile ducts.
BENIGN NEOPLASMS :Cavernous hemangiomas : Blood vessel tumors. Red -blue soft nodules, less than 2 cm. Often occur directly beneath the capsule. Not be mistaken for metastatic tumors. Blind percutaneous biopsies not be performed on them.
Liver cell adenomas: Benign neoplasms developing from hepatocytes. Occur in young women who used oral contraceptivesand regress on discontinuance of their use. When present as intrahepatic mass, may be mistakenfor hepatocellular carcinoma. Subcapsular adenomas have tendency to rupture. Rarely, may harbor hepatocellular carcinoma.
Morphology:Grossly:• Yellow-tan bile-stained nodules, often presentbeneath capsule.• Usually well demarcated, encapsulationmight not be present.Microscopically :• Sheets and cords of cells that may resemble normalhepatocytes or have some variation in cell and nuclear size.• Abundant glycogen generate a clear cytoplasm.• Portal tracts are absent.
MALIGNANT TUMORS:Hepatoblastoma : Most common liver tumor of young childhood. Usually fatal within few years if not resected. Has two variants:o Epithelial type:composed of small polygonal fetal cells forming acini,tubules, or papillary structures resembling liver development.o Mixed epithelial and mesenchymal type:contains foci of mesenchymal differentiation thatmay consist of primitive mesenchyme, osteoid, cartilage,or striated muscle.
Hepatoblastoma revealing thepresence of embryonal epithelial cellsarranged in sheets.Mesenchymal component including osteoidmaterial in mixed type hepatoblastoma
Angiosarcoma : Resembles those occurring elsewhere. Its association with exposure to vinyl chloride,arsenic, or Thorotrast (formerly used in radiography). Latency period after exposure may be several decades. Highly aggressive neoplasms metastasize widelyand generally kill within a year.
Hepatocellular Carcinomas : Constitute 5.4% of all cancers in human. Blacks affected threefold higher than others . Male predominance . Three major etiologic associations :-1- viral infection (HBV, HCV).2- chronic alcoholism .3- food contaminants ( aflatoxins ).Others include : tyrosinemia and hereditaryhemochromatosis.
Morphology:Grossly:(1) unifocal (usually large) mass.(2) multifocal nodules of variable size.(3) diffusely infiltrative cancer.Microscopically: Range from well-differentiated to highly anaplasticundifferentiated lesions. In well-differentiated and moderately differentiated tumors,cells are disposed either in trabecular pattern(recapitulating liver cell plates) or in acinar pattern . In poorly differentiated forms, tumor cells arepleomorphic with numerous anaplastic giant cells.
H.C.C- acinar and trabecular patterns Poorly differentiated H.C.C
Fibrolamellar carcinoma: Variant of hepatocellular carcinoma. Occurs in young male and female (20 to 40 years )with equal incidence. No association with HBV or cirrhosis risk factors,and has better prognosis. Grossly: Presents as single large hard "scirrhous" tumorwith fibrous bands coursing through it.
Microscopically: composed of well-differentiatedpolygonal cells growing in nests or cords and separatedby parallel lamellae of dense collagen bundles .
Clinical Features of H.C.C: Upper abdominal pain. Malaise, fatigue, weight loss. abdominal mass or abdominal fullness. Jaundice, fever, and esophageal variceal bleeding.Lab. studies: Elevated levels of serum α-fetoprotein (in 50% to 75%of patients ). False -positive results: in yolk-sac tumors andnon-neoplastic conditions( cirrhosis, massive liver necrosis,chronic hepatitis, and normal pregnancy). Radiologic studies: US, hepatic angiography , CT scan,and MRI.
Prognosis: Hematogenous metastases: especially to lung,occur late in disease. Lymph node metastases: to perihilar, peripancreatic,and para-aortic nodes in less than half of cases. Death occurs from:(1) cachexia(2) GIT or esophageal variceal bleeding.(3) liver failure with hepatic coma.(4) rarely, rupture of tumor with fatal hemorrhage. Fibrolamellar variant has favorable outlook.
Metastatic Tumors: More common than primary neoplasia. Most common primaries: breast, lung, and colon. Metastasis may be present in absence of clinical orlab. evidence of hepatic functional insufficiency. However, with massive destruction of liver substanceor direct obstruction of major bile ducts, jaundiceand elevations of liver enzymes may appear.
Summary:1. α1- antitrypsin deficiency is a metabolic liver disease.2. Intrahepatic biliary tract diseases : primary andsecondary biliary cirrhosis, and primary sclerosingcholangitis.3. Benign tumors of liver: cavernous hemangioma, andliver cell adenomas.4. Malignant tumors : Hepatoblastoma, Angiosarcoma,and H.C.C.5. Metastatic tumors to liver are more common thanprimary neoplasia.
Questions:1. Mention morphological changes of hepatocellularcarcinoma?2. Write short assay on primary biliary cirrhosis?THANK YOU