What is the next step in management for a patient with hepatic masses on ultrasound, potentially indicating hepatocellular carcinoma (HCC) or other liver lesions, with possible chronic liver disease or risk factors for HCC?

Management of Hepatic Masses on Ultrasound

For hepatic masses detected on ultrasound, proceed immediately to multiphasic contrast-enhanced CT or MRI to characterize the lesion, with the specific management pathway determined by lesion size, presence of cirrhosis, and imaging characteristics. 1, 2

Initial Risk Stratification

The presence or absence of chronic liver disease fundamentally changes your diagnostic approach and threshold for concern:

• In cirrhotic patients or those with chronic hepatitis B/C, any nodule >1 cm has significant malignancy risk and requires immediate dynamic imaging workup 3
• In non-cirrhotic patients without cancer history, 78-84% of small hypodense lesions prove benign, but dynamic imaging is still required for definitive characterization 1
• Check AFP level - while not diagnostic alone (elevated in only 50-75% of HCC cases), AFP ≥200 ng/mL combined with typical imaging features allows HCC diagnosis without biopsy in cirrhotic patients 3

Size-Based Diagnostic Algorithm

Lesions <1 cm

• Too small to characterize definitively - the majority are not HCC even in cirrhotic livers 3, 1
• Implement surveillance protocol: Repeat ultrasound every 3-4 months for non-cirrhotic patients, every 3 months for cirrhotic patients 3, 1
• Do not proceed to biopsy - technical difficulty, high false-negative rate, and risk of needle-track seeding make this inappropriate 1
• If no growth over 1-2 years, resume routine surveillance 1

Lesions 1-2 cm

• Obtain multiphasic CT or MRI immediately looking for arterial hyperenhancement with portal venous/delayed washout 3, 2
• In cirrhotic patients: One imaging technique showing characteristic HCC features (arterial hyperenhancement with washout) is sufficient for diagnosis 3, 1
• If imaging is atypical or indeterminate: Obtain a second dynamic study with the alternate modality (CT if MRI was first, or vice versa) 3
• If both studies show typical HCC features, diagnose as HCC without biopsy 3
• If imaging remains non-diagnostic, proceed to image-guided core biopsy (not fine needle aspiration) 3, 2

Lesions >2 cm

• In cirrhotic patients with AFP ≥200 ng/mL: One dynamic imaging study showing typical HCC features is sufficient for diagnosis without biopsy 3, 2
• In cirrhotic patients with AFP <200 ng/mL: Typical HCC features on one dynamic imaging study is still sufficient for diagnosis 3, 1
• If imaging shows atypical features, obtain second imaging modality or proceed to core biopsy 3, 2
• In non-cirrhotic patients: Multiphasic imaging is essential to differentiate between hemangioma (peripheral nodular enhancement with centripetal fill-in), focal nodular hyperplasia (intense arterial enhancement with central scar), HCC, cholangiocarcinoma, or metastases 1, 2

Key Imaging Characteristics

Typical HCC Pattern

• Arterial phase: Hyperenhancement due to abnormal arterial neovascularization 3, 1
• Portal venous/delayed phase: Washout (becomes hypoenhancing relative to liver) 3, 1
• Additional features: May show mosaic pattern, septations, peripheral halo, or daughter nodules 3

Benign Lesions to Recognize

• Hemangioma: Peripheral nodular enhancement with progressive centripetal fill-in on delayed phases - do not biopsy these 1
• Focal nodular hyperplasia: Intense arterial enhancement becoming isoattenuating in portal venous phase, often with central scar 1
• Simple cysts: No enhancement in any phase, clearly defined perfusion defects 3
• Abscess: Arterial rim enhancement with rapid washout and central non-enhancement 3

Role of Biopsy

Biopsy is indicated only when:

• Diagnosis remains uncertain after two dynamic imaging studies AND the diagnosis will alter management 1, 2
• Patient is proceeding to systemic chemotherapy or clinical trial enrollment 1
• Lesion shows atypical features raising concern for cholangiocarcinoma or metastasis 3, 2

Critical biopsy caveats:

• Always use core biopsy, never fine needle aspiration alone - FNA is insufficient for definitive diagnosis 1
• Biopsy of lesions <1 cm is unreliable due to sampling error and difficulty distinguishing well-differentiated HCC from dysplastic nodules 3, 1, 2
• If biopsy is negative but suspicion remains high, continue imaging surveillance every 3-6 months and repeat biopsy if the lesion enlarges or develops typical HCC features 3

Contrast-Enhanced Ultrasound (CEUS) Considerations

• CEUS can correctly characterize 89% of focal liver lesions and distinguish benign from malignant in 97% of cases 3
• Asian guidelines permit CEUS for HCC surveillance in patients with very coarse liver parenchyma, though it is not routinely recommended in North America 3
• CEUS was removed from AASLD guidelines due to false-positive HCC diagnosis in cholangiocarcinoma cases 3
• If CEUS is used, typical HCC shows arterial hypervascularity with early washout in portal venous phase 3

Critical Pitfalls to Avoid

• Do not assume all masses are benign cysts - any solid or complex lesion requires multiphasic imaging 1
• Do not rely on AFP alone - sensitivity is only 50-75% for HCC, and imaging is essential 3, 4
• Do not biopsy suspected hemangiomas - characteristic enhancement pattern on multiphasic imaging is diagnostic 1
• Do not delay dynamic imaging in cirrhotic patients - any nodule >1 cm requires immediate workup, as 87.6% of nodules in cirrhotic livers prove to be HCC 5
• Do not use single-phase CT - triphasic/multiphasic imaging is essential to detect arterial hypervascularity and washout patterns 3, 6
• Do not perform biopsy on lesions <1 cm - high false-negative rate and risk of seeding 1

Follow-Up for Indeterminate Lesions

If initial advanced imaging is indeterminate after two modalities:

• Continue imaging surveillance every 3-6 months for up to 2 years 2
• Consider biopsy if: Lesion shows growth, develops arterial hyperenhancement, or patient has high-risk features 2
• In cirrhotic patients, maintain closer 3-month surveillance intervals 1