Tumors and tumor-like lesions of the liver

1. Tumor-Like Lesions (Hepatocellular Nodules)

A) Focal nodular hyperplasia (FNH)

• Localized, well-demarcated but poorly encapsulated lesion of hyperplastic hepatocytes around a central fibrous scar.
• Not a true tumor — reactive to local vascular injury.
• More common in women.
• No malignant risk.

B) Dysplastic nodules

• > 1 mm lesions in cirrhotic livers.
• Hepatocytes highly proliferative with atypia, crowding, polymorphism.
• High-grade dysplasia = precursor of HCC.

C) Macro-regenerative nodules

• Appear in cirrhotic liver.
• Larger than surrounding cirrhotic nodules but no atypia.
• Contain >1 portal tract.
• Not precursors of malignancy.

2. Benign Tumors

A) Cavernous hemangioma

• Most common benign liver tumor.
• Well-circumscribed, red-blue soft nodule, usually < 2 cm, directly beneath capsule.
• Endothelium-lined vascular channels + stroma.
• Caution: biopsy contraindicated (bleeding risk).

B) Hepatocellular adenoma

• Young women on OCPs → may regress with discontinuation.
• Pale, yellow-tan, well-demarcated nodules.
• Histology: sheets/cords of hepatocyte-like cells with mild atypia.
• Clinical concern:
  • May be mistaken for HCC.
  • Large tumors → risk of rupture / hemoperitoneum (esp. pregnancy).
  • Subtypes with β-catenin mutation → risk of malignant transformation.

3. Malignant Tumors — Hepatocellular Carcinoma (HCC)

• Most common primary liver malignancy.

Causes (RF)

• HBV or HCV infection
• Aflatoxin (from Aspergillus on peanuts / moldy grains → p53 mutation)
• Chronic alcoholism / cirrhosis of any cause
• Hemochromatosis, NAFLD, α1-AT deficiency, Wilson (any cirrhosis)

Pathogenesis

• Arises from small-cell, high-grade dysplastic nodules in cirrhotic livers.
• Structural + numerical chromosomal abnormalities nearly universal.
• Driven by chronic cell death + regeneration + inflammation.

Morphology

• Gross patterns: unifocal (massive) / multifocal (multiple nodules) / diffusely infiltrative.
• Yellow-white nodules in cirrhotic background; intrahepatic vascular invasion (portal vein).
• Histology: poorly to highly differentiated.
• Fibrolamellar carcinoma — variant:
  • Younger patients (no cirrhosis), polygonal cells with lamellated fibrosis, better prognosis.

Clinical features

• Often discovered on background of cirrhosis.
• Rapid ↑ liver size, sudden worsening of ascites, bloody ascites, fever, pain.
• Tumor marker: ↑ α-fetoprotein (AFP).
• Death: profound cachexia, variceal bleeding, liver failure with hepatic coma, tumor rupture with fatal hemorrhage.
• Tx: segmental resection or transplantation.

4. Cholangiocarcinoma

• 2nd most common primary liver cancer after HCC.
• Adenocarcinoma with biliary differentiation arising from cholangiocytes of intra-/extrahepatic ducts.
• Often asymptomatic until advanced → frequently unresectable → poor prognosis.
• RF: PSC, chronic biliary inflammation, liver flukes.

5. Metastatic Tumors

• Liver involved in ~ 1/3 of all metastatic cancers.
• Common primaries: GI tract, breast, lung, pancreas, malignant melanoma.
• Primary vs metastatic clue: HCC arises in cirrhotic liver; mets are rare in cirrhotic liver → tumor + cirrhosis → probably primary; tumor + non-cirrhotic liver → probably metastatic.

💡 High-yield: Cavernous hemangioma = most common benign (no biopsy). Hepatocellular adenoma = young ♀ on OCPs, rupture risk. HCC = #1 primary malignancy; RF HBV/HCV, aflatoxin, cirrhosis (any cause); marker AFP; fibrolamellar subtype = young, no cirrhosis, better prognosis. Cholangiocarcinoma = #2 primary, RF PSC, poor prognosis. Mets > primary: in non-cirrhotic liver → think metastatic; in cirrhotic → think HCC.