Approach to the Liver Biopsy

The Liver Biopsy

  • Architecture – Ishak stage for cirrhosis
  • Inflammation – periportal, interface, lobular inflammation (Necroinflammatory & Total Ishak score)
  • Hepatocyte death – Apoptosis, Ballooning degeneration, Necrosis, Kupffer cells with lipofuscin
  • Sinosoidal dilatation, Liver cell plate thickening.
  • Steatosis (micro/macrovesicular)
  • Cholestasis, Haemasiderosis, Lipofuscin

Special Stains

  • Masson Trichrome – Fibrosis, Also helpful to assess portal tract (bile ductule, arteriole & venule)
  • Orcein – Cu assoc protein, HbsAg, Elastic fibres, granular staining of hepatocytes in cirrhosis, bile duct destruction and wilsons due to effects on cytochrome p450 system with effects on copper metabolism.
  • DPAS – DPAS positive periportal intracytoplasmic granules in alpha1-AT def, Shows macrophage phagocytosis of hepatocytocytes and is an indicator of hepatocyte loss.
  • Pearl’s – Fe
  • Reticulin – Liver cell plate thickness

Classical appearances:

Alcoholic Liver Disease – Macrovesicular Steatosis, Inflammation (Zone 3 – perivenular), Mallory’s hyaline, Ballooning degeneration, neutrophilic reaction, fibrosis and then cirrhosis.

Non-Alcoholic Steatoheapatitis – Macrovesicular Steatosis & Inflammation. Assoc with metabolic syndrome – obesity, insulin resistance & diabetes

Autoimmune Hepatitis – Periportal plasma cells

Primary Biliary Cirrhosis – Variably involved granulomatous inflammation of bile ducts. Increased anti-mitochondrial antibody. More common in women. Tends to affect smaller ducts. Ductopenia.

Primary Sclerosing Cholangitis – Periductal portal tract fibrosis (onion skin fibrosis). Assoc with ulcerative colitis. More common in men. Tends to affect larger ducts. Variable necro-inflammatory bile duct destruction. Ductopenia.

Cirrhosis – Bridging fibrosis, parenchymal nodules (due to hepatocyte death, ECM deposition & vascular re-organisation

Active Hepatitis – Periportal inflammation and interface hepatitis, ballooning degeneration. cholestasis, Apoptosis, Bridging necrosis, Kupffer cell hypertrophy and hyperplasia and laden with lipofuscin. Kupffer cells staining positive on DPAS – showing phagocytosis of hepatocytes – evidence of hepatocyte death. Thickening of liver cell plates on reticulin – lobular disarray – regenerative change.

Active chronic hepatitis progressing to cirrhosis – DD Viruses, Autoimmune, Drugs

Hepatitis B – Cytoplasm packed with HbsAg has a finely granular “ground-glass” appearance.

Hepatitis C – Lymphoid aggregates within portal tracts and focal lobular regions of hepatocyte macrovesicular steatosis.

Von Meyenburg Complex – Bile duct hamartoma. Dilated and irregularly shaped bile ducts in a fibrous stroma

Hereditary Haemochromotosis – Deposition of haemosiderin the liver, pancreas, myocardium, pituitary, adrenal , thyroid, parathyroid, joints, skin. Mutations encoding HFE, transferrin receptor 2 or hepcidin. Haemojuvelin in juvenile haemochromatosis.

Wilson Disease – Accumulation of Cu in the liver, brain & eye due to failure to incorporate Cu into caeruloplasmin. Caused by mutation of ATP7B gene. Deposition of Cu in the basal ganglia of the brain & Descemet’s membrane in the limbus of the cornea – Kayser -Fleischer rings.

Alpha 1-Antitrypsin deficiency – Periportal intracytoplasmic DPAS positive granules. Autosomal recessive disorder assoc with low Alpha1AT with inhibits proteinases. PiMZ &PiSZ genotypes typically less severe. PiZZ homozygotes more severe but varied.

Acute rejection in a transplanted liver – Mixed inflammatory cell infiltrate including eosinphils in portal tracts, bile duct damage & endothelitis. BANFF grade.

Acute/Chronic GvHD – Acute 10-50 days post bone marrow transplant – assoc with inflammation, necrosis of hepatocytes & bile ducts. Chronic – >100days post – assoc with portal tract inflammation, selective bile duct destruction & fibrosis.

Acute fatty liver of pregnancy – Microvesicular steatosis

Reye syndrome- Mitochondrial dysfunction in liver & brain. Mainly in children. Assoc with aspirin. Microvesicular steatosis.

Focal Nodular Hyperplasia – Has a lobulated contour and central stellate scar. Assoc with anabolic hormones & OCP.

Nodular Regenerative Hyperplasia – Liver transformed into roughly spherical nodules in the abscence of cirrhosis. Tends to be diffuse. Reticulin stain to appreciate change in architecture. Can lead to portal hypertension. Assoc with conditions that affect intrahepatic blood flow – renal transplantation, bone marrow transplantation & vasculitis, also HIV.

Hepatic Adenoma – Typically a solitary well demarcated lesion often beneath the capsule. Consists of sheets and cords of cells that resemble normal hepatocytes. Portal tracts are absent and instead prominent solitary arterial vessles and draining veins are distributed throught the substance of the tumour. Assoc with OCP. Risk of rupture particularly at pregnancy. Risk of malignant transformation when arises in individuals with glycogen storage disorders or B catenin mutation.

HCC – Unifocal, multifocal or diffusely infiltrative pattern. All patterns have a strong propensity for invasion of vascular structures. May range from well diff to anaplastic.

Fibrolamellar carcinoma (Variant of HCC) – In young (20-40yr old) men & women. Usually no underlying  chronic liver disease so better prog than conventional HCC. Tumour shows well differentiated polygonal cells growing in nest or cords separated by parallel lamellae of dense collagen bundles. The tumour cells have abundant eosinophilic cytoplasm and prominent nucleoli.

Reference:

Robbins & Cotran. Pathologic Basis of Disease.

Advertisements
This entry was posted in Hepatobiliary. Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s