Liver Tumours

Classification

Benign Tumours

1. Cavernous Haemangioma

• Symptoms: The vast majority are asymptomatic. Symptoms (pain, fullness, nausea) are linked to stretch of Glisson's capsule. Giant haemangiomas (>10 cm) can rarely cause biliary obstruction or Budd-Chiari syndrome.
• Diagnosis: Imaging (US, CT, MRI) is usually diagnostic without biopsy.
• Kasabach-Merritt syndrome: Rare — thrombocytopenia from platelet sequestration within the lesion.
• Management: Observation for asymptomatic lesions. If surgery is needed, enucleation or parenchymal resection are both options.
• Key distinction: Must be differentiated from metastatic tumours radiographically or intraoperatively.

2. Hepatocellular Adenoma (HA)

• Risk factors: Historically associated with oral contraceptive use (high-oestrogen pills); now more strongly linked to obesity and metabolic syndrome. Oestrogen stimulates growth.
• Driver mutations: β-catenin gain-of-function mutations, among others.
• Morphology: Ranges from sheets of normal-appearing hepatocytes to tumours with significant cytologic atypia. No portal tracts; arterial supply only.
• Complications:
  • Rupture → life-threatening intraabdominal haemorrhage
  • Malignant transformation (especially in β-catenin-mutated adenomas)
  • Rupture risk is increased during pregnancy (high maternal and fetal mortality)
• Management: Lesions >5 cm or those with β-catenin mutations are typically resected. OCP cessation is advised. Surveillance imaging for smaller lesions.

Hepatic adenoma: (A) Resected specimen. (B) Cords of hepatocytes with arterial vascular supply (arrow) and no portal tracts.

3. Focal Nodular Hyperplasia (FNH)

• A well-demarcated, poorly encapsulated nodule in an otherwise normal liver, most frequent in young to middle-aged adults.
• Hallmark: Central gray-white stellate scar with fibrous septa radiating to periphery; large abnormal vessels and ductular reactions within the central scar.
• Clinically benign; rarely requires resection. Surgery may be considered when it cannot be distinguished from hepatic adenoma or fibrolamellar HCC on imaging.

Focal nodular hyperplasia: central stellate scar (A) with broad fibrous scar and ductular elements (B).

Primary Malignant Tumours

1. Hepatocellular Carcinoma (HCC)

Epidemiology

• Highest incidence in Southeast Asia, Korea, Taiwan, and sub-Saharan Africa (endemic HBV), with peak onset at 20–40 years. In these regions, ~50% of cases arise without cirrhosis.
• In Western countries, HCC incidence tripled recently, driven largely by HCV. Almost 90% of Western cases emerge after established cirrhosis; peak onset is after 60 years.
• Male predominance: 3:1 (low-incidence areas) to 8:1 (high-incidence areas).

Risk Factors

Pathogenesis

Morphology

• Gross: Unifocal, multifocal, or diffusely infiltrating masses. Tumours are often soft, haemorrhagic, and have areas of necrosis. A nodule-in-nodule pattern suggests evolving cancer.
• Histology: Well-differentiated tumours resemble hepatocytes; may show trabecular or pseudo-glandular (acinar) patterns. Bile production is a useful diagnostic feature.
• Fibrolamellar HCC: A distinct variant — occurs in younger patients, those without cirrhosis, and without chronic liver disease. Better prognosis.
• Vascular invasion: Very common; portal vein invasion → intrahepatic spread.
• Metastases: Lung, peritoneum, bone, spleen, adrenal gland, brain.

HCC: (A) Nodule-in-nodule growth pattern. (B) Well-differentiated HCC adjacent to a sub-nodule of more poorly differentiated cells.

Diagnosis & Staging

• In chronic liver disease, CT and MRI are typically diagnostic without biopsy: look for arterial hyperenhancement + portal venous washout.
• LI-RADS 5 = diagnostic of HCC.
• Tumour markers: AFP (alpha-fetoprotein) is the primary marker; CA 19-9 and CEA if diagnosis is unclear.
• Staging: AJCC, Barcelona Clinic Liver Cancer (BCLC), and Okuda staging systems. BCLC also incorporates degree of chronic liver disease.

Management

• Perioperative mortality for major hepatectomy is <5% in Child-Pugh A without portal hypertension, but increases significantly in Child-Pugh B/C.
• No proven adjuvant systemic therapy exists for resected HCC currently.

2. Cholangiocarcinoma (CCA)

• Intrahepatic CCA: Arises from intrahepatic bile ducts; presents as a hepatic mass.
• Perihilar (Klatskin tumour) and distal CCA: At the biliary confluence and distal CBD respectively.
• Risk factors: Primary sclerosing cholangitis (PSC), liver flukes (Opisthorchis, Clonorchis), choledochal cysts, chronic HBV/HCV.
• Often presents late; poor prognosis. Surgical resection is the only curative option.

3. Hepatoblastoma

• The most common primary liver malignancy in children (usually <5 years of age).
• Two main subtypes: epithelial (most common) and mixed epithelial-mesenchymal.
• Treated with chemotherapy + surgical resection. Complete resection before drug resistance develops is essential for survival.

Metastatic Tumours

• Colorectal cancer (most surgically resectable)
• Breast, lung, pancreas, stomach, carcinoid/NETs

Diagnostic Imaging Summary

Liver Tumours — USMLE Step 1

Benign Tumours

Primary Malignant Tumours

Hepatocellular Carcinoma (HCC)

• Most common primary liver malignancy worldwide
• Risk factors: HBV (can cause HCC without cirrhosis), HCV (needs cirrhosis), aflatoxin (Aspergillus), alcohol, NAFLD, haemochromatosis, α1AT deficiency
• AFP is the tumour marker
• Imaging: Arterial hyperenhancement + portal venous washout → LI-RADS 5 = diagnostic
• Microscopy: Trabecular pattern, bile production, no portal tracts
• Spread: Portal vein invasion (intrahepatic); mets to lung, bone, adrenal
• Fibrolamellar HCC: Young patients, NO cirrhosis, better prognosis

Cholangiocarcinoma

• Bile duct origin
• Risk factors: PSC, liver flukes (Clonorchis, Opisthorchis), choledochal cysts
• Perihilar = Klatskin tumour

Hepatoblastoma

• Most common liver malignancy in children <5 years
• Elevated AFP
• Treat with chemo + resection

Metastatic Tumours

• Most common hepatic malignancy overall (more common than primaries)
• Sources: colorectal > breast > lung > pancreas
• Colorectal mets = most resectable

High-Yield Associations

α1-Antitrypsin Deficiency — USMLE Step 1

Core Concept

Genetics

Two Mechanisms, Two Organs

Key distinction: Lung disease = lack of protein. Liver disease = too much misfolded protein.

Liver Disease

• Most common inherited hepatic disorder in infants and children
• Neonates: hepatomegaly, cholestatic jaundice (10–20%)
• Adolescents/adults: chronic hepatitis, cirrhosis, HCC (2–3% of PiZZ adults)
• Only 10–15% of PiZZ individuals develop overt liver disease (other genetic/environmental factors involved)
• Treatment: Liver transplantation (curative for liver disease; does NOT help lungs)

Lung Disease

• Emphysema develops in adults
• Panacinar emphysema, lower lobe predominant (vs. upper lobe in smoking-related centriacinar emphysema)
• May also develop bronchiectasis
• Smoking dramatically accelerates lung disease (neutrophil accumulation → more elastase release)

Histology (High-Yield)

• Liver biopsy: Round-to-oval cytoplasmic globular inclusions in hepatocytes
• Stain: PAS-positive, diastase-resistant (magenta globules)
• Periportal hepatocytes affected first

α1AT deficiency: PAS stain after diastase digestion showing characteristic magenta cytoplasmic globules in hepatocytes.

High-Yield Associations