Pathology of Liver Diseases

Inflammatory & Autoimmune Conditions

Disease Key Histological Findings Buzzwords / Stains
Acute Viral Hepatitis - Panlobular inflammation (lymphocytic) & hepatocyte necrosis.
- Lobular disarray; ballooning degeneration of hepatocytes.
- Apoptotic bodies (Councilman bodies).
- +/- Cholestasis.		 - "Spotty necrosis," lobular disarray.
- Bridging necrosis (severe cases).
Chronic Viral Hepatitis - Portal tract inflammation (predominantly lymphocytic).
- Interface hepatitis ("piecemeal necrosis"): inflammation spills from portal tracts into the adjacent parenchyma.
- Fibrosis progressing from portal tracts to cirrhosis.
- HBV: "Ground-glass" hepatocytes (HBsAg accumulation).
- HCV: Lymphoid aggregates/follicles in portal tracts, macrovesicular steatosis, bile duct damage.		 - Interface hepatitis.
- Ground-glass hepatocytes (HBV).
- Lymphoid aggregates (HCV).
Autoimmune Hepatitis (AIH) - Dense lymphoplasmacytic infiltrate in portal tracts and extending into the lobule.
- Severe interface hepatitis is characteristic.
- Hepatocyte rosetting (regenerative clusters).
- Emperipolesis (lymphocytes within hepatocyte cytoplasm).		 - Prominent plasma cells.
- Hepatocyte rosettes.

Steatotic Liver Diseases

Disease Key Histological Findings Buzzwords / Stains
Alcoholic Liver Disease (ALD) - Steatosis: Macrovesicular fat, predominantly centrilobular (Zone 3).
- Steatohepatitis (ASH): Hepatocyte ballooning, Mallory-Denk bodies (intracytoplasmic eosinophilic inclusions), neutrophilic infiltrate.
- Fibrosis: Perivenular and pericellular ("chicken-wire") fibrosis in Zone 3, progressing to cirrhosis.		 - Mallory-Denk bodies.
- Neutrophilic inflammation.
- Sclerosing hyaline necrosis.
- Centrilobular (Zone 3) accentuation.
Non-alcoholic Fatty Liver Disease (NAFLD/NASH) - NAFL: Macrovesicular steatosis (>5% of hepatocytes).
- NASH: Steatosis + inflammation (lobular, mixed) + hepatocyte injury (e.g., ballooning).
- Mallory-Denk bodies may be present but are often less prominent than in ALD.
- Fibrosis: Perisinusoidal/pericellular ("chicken-wire") pattern, often starting in Zone 3.		 - Indistinguishable from ALD on histology alone; requires clinical correlation (absence of significant alcohol use).

Cholestatic & Biliary Diseases

Disease Key Histological Findings Buzzwords / Stains
Primary Biliary Cholangitis (PBC) - Autoimmune destruction of small to medium intrahepatic bile ducts.
- Florid duct lesion: Lymphocytic cholangitis with or without granulomas attacking a bile duct.
- Ductopenia (loss of bile ducts) in later stages.
- Portal inflammation (lymphocytes, plasma cells, eosinophils).		 - Florid duct lesion.
- Granulomatous destruction of bile ducts.
- AMA positive.
Primary Sclerosing Cholangitis (PSC) - Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts.
- Periductal concentric fibrosis ("onion-skinning") around bile ducts.
- Progressive obliteration of ducts, leaving a fibrous cord (fibro-obliterative lesion).
- Ductopenia is common.		 - "Onion-skin" fibrosis.
- Beaded appearance on ERCP/MRCP.

Metabolic & Genetic Diseases

Disease Key Histological Findings Buzzwords / Stains
Hereditary Hemochromatosis (HH) - Heavy iron deposition primarily in hepatocytes (parenchymal pattern), particularly in a periportal (Zone 1) distribution.
- Iron also seen in bile duct epithelium and Kupffer cells as disease progresses.
- Eventually leads to micronodular cirrhosis.		 - Prussian blue stain highlights hemosiderin (iron) as blue granules.
Wilson Disease - Findings are highly variable; can mimic steatohepatitis, chronic hepatitis, or cirrhosis.
- Features include macrovesicular steatosis, hepatocyte necrosis, glycogenated nuclei, and Mallory-Denk bodies.
- Copper accumulation may be demonstrable but is often uneven.		 - Nonspecific findings; high index of suspicion needed.
- Rhodanine or Orcein stain for copper (positive staining is confirmatory, but negative does not exclude).
Alpha-1 Antitrypsin (A1AT) Deficiency - Round, eosinophilic, PAS-positive, diastase-resistant (PAS-D+) globules within the cytoplasm of periportal hepatocytes.
- These globules are aggregates of the misfolded A1AT protein in the endoplasmic reticulum.
- Can lead to cholestasis in neonates or cirrhosis in adults.		 - PAS-D positive globules in periportal hepatocytes.

Neoplastic Diseases

Disease Key Histological Findings Buzzwords / Stains
Hepatocellular Carcinoma (HCC) - Tumor cells resemble hepatocytes, often arranged in thickened trabeculae (>3 cells thick), solid, or pseudo-glandular patterns.
- Loss of reticulin framework.
- Sinusoidal capillarization (positive for CD34).
- May produce bile.		 - Thickened trabeculae.
- Polygonal cells with eosinophilic cytoplasm.
- Bile production by tumor cells.
Cholangiocarcinoma (CCA) - Adenocarcinoma forming glandular or duct-like structures.
- Associated with a dense, desmoplastic (fibrous) stroma.
- Tumor cells are cuboidal to columnar and often mucin-producing.
- Perineural and lymphovascular invasion are common.		 - Glandular structures.
- Desmoplastic stroma.
- Mucin production.