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Liver and intrahepatic bile ducts-nontumor
Patterns of hepatic injury
Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 21 April 2012, last major update April 2012-IN PROGRESS
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.
Acidophil body
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● Type of focal necrosis in which dead hepatocyte is identifiable as shrunken, eosinophilic round body with variable nucleus, usually not accompanied by inflammation
● Also called Councilman body, single cell death, apoptotic cell
● Signifies nonspecific hepatocellular injury
Ballooning (feathery) degeneration
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● Swelling of hepatocytes with increased and pale cytoplasm, nonspecific
● Leads to lytic necrosis and replacement by inflammatory cells
Feathery (ballooning) degeneration
Bile ductules
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● Proliferate in pathologic conditions, and can differentiate into hepatocytes to repopulate a destroyed liver
● Small ovoid cells lying singly at periphery of portal tract or as strings within the lobule; not accompanied by artery
● Mild bile ductular proliferation may be due to obstruction without bile duct disease (Mod Pathol 2004;17:874)
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Bile ductules due to chronic hepatitis C
Bile ductular proliferation due to obstruction
Bile ductules due to focal nodular hyperplasia (H&E, CK7)

Bile ductules (CK7+) due to sarcoidosis
Bridging necrosis
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● May also be called confluent
● Necrotic cells spans adjacent lobules in portal-portal, portal-central or central-central pattern (Am J Dig Dis 1978;23:1076)
Centrilobular necrosis
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● Necrotic hepatocytes around central vein, usually due to ischemia, drugs or toxins
● Common finding at autopsy, because it is associated with circulatory failure or shock which is common before all deaths
● Distinguish from coagulative necrosis (hepatocytes are necrotic away from central vein)
Centrilobular (left) versus coagulative necrosis (right)
Giant cell transformation
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● Hepatocyte with 6 or more nuclei (Ann Hepatol 2009;8:68)
Glycogen nuclei
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● Homogenous clearing of hepatocyte nuclei, usually with enlargement, usually periportal
● Seen in most biopsies in a few nuclei
● Abundant in hyperglycemia, glycogen storage disease, Wilson’s disease, nonalcoholic steatohepatitis
Interface hepatitis
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● Inflammatory cells between inflamed portal tracts and periportal parenchyma
Interlobular bile duct
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● Bile duct of medium sized portal tract that is centrally located in tract and accompanies similarly sized arteriole
Large cell change
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● Also called large cell dysplasia
● Atypical hepatocytes with nuclear and cytoplasmic enlargement, nuclear pleomorphism with hyperchromasia, multinucleation but normal nuclear to cytoplasmic ratio
● Often periseptal; doesn’t deform surrounding architecture
● May be associated with prolonged cholestasis
● Appears to NOT be a premalignant condition (Hum Pathol 2009;40:1774)
Mallory’s hyaline
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● Also called Mallory bodies
● Irregular, rope-like, sharply defined, intracytoplasmic eosinophilic deposits of cytokeratin, may assume C-shape around nucleus, often in ballooning cells, surrounded by neutrophils in alcoholic liver disease
● Associated with alcoholic and nonalcoholic steatohepatitis, various cholestatic conditions, Wilson’s disease
● Positive stains: CK8, ubiquitin
Microvesicular steatosis
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● Multiple tiny intracytoplasmic fat droplets that do not displace the nucleus
● May be so small that they simulate ballooning degeneration
● Associated with alcoholic liver disease, acute fatty liver of pregnancy, outdated tetracycline, valproic acid, Reye’s syndrome, nucleoside analog therapy for HIV (Arch Pathol Lab Med 1999;123:189, Mod Pathol 2007;20 Suppl 1:S40)
Microvesicular steatosis

Virtual slide
Macrovesicular steatosis
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● Single large intracytoplasmic fat droplet that displaces nucleus; associated with alcoholic liver disease, obesity, diabetes, nonalcoholic steatohepatitis, drug reactions, cystic fibrosis
Macrovesicular steatosis

Left: Oil Red O (fat) stain; right: virtual slide
Necrosis
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● Bridging necrosis (joins structures such as portal tracts), centrilobular necrosis and coagulative necrosis are described above; submassive necrosis is described below
● Focal necrosis: individual hepatocytes, usually apoptosis (see acidophil body above)
● Massive necrosis: all hepatocytes in biopsy
● Piecemeal necrosis: affects hepatocytes at limiting plate; either necrosis of cells or irregularity of limiting plate caused by loss of hepatocytes and replacement with inflammatory cells or fibrosis; usually minimal lobular inflammation is present) or zonal (specific region such as centrilobular)
Focal necrosis
Massive necrosis
Piecemeal necrosis
Passive congestion
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● Common finding at autopsy, because associated with circulatory failure which is common before all deaths
● Also called nutmeg liver
● Due to right sided cardiac decompensation
● Liver large, tense, cyanotic around edges with congestion of centrilobular sinusoids
● Over time, develops centrilobular necrosis
Nutmeg liver

Chronic passive congestion
Small cell change
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● Also called small cell dysplasia
● Small hepatocytes with increased nuclear density
● May have basophilic cytoplasm, but no significant nuclear atypia or enlargement
● Usually present in clusters
● Found in regeneration, atrophy, premalignant or malignant conditions (Oncol Rep 2010;23:1229)
Submassive necrosis
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● Prominent necrosis involving centrilobular zones or entire lobules in most of liver: associated with hepatic failure
● May also be called confluent necrosis
● Bile ductular proliferation prominent in necrotic zones in late stages
● No significant collagen or elastic fiber deposition
● Collapse of reticulin network in necrotic zones
End of Liver and intrahepatic bile ducts-nontumor > Patterns of hepatic injury
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