What are the imaging mimics of hepatocellular carcinoma in LI-RADS category 5 lesions?

Mimics of Hepatocellular Carcinoma in LI-RADS 5 Lesions

Despite LI-RADS 5 criteria being designed for high specificity (98.5% for HCC), several important mimics can still present with arterial phase hyperenhancement and late mild washout, most notably inflammatory hepatocellular adenoma in cirrhotic patients, small duct intrahepatic cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma. 1, 2, 3

Primary Malignant Mimics

Small Duct Intrahepatic Cholangiocarcinoma (iCCA)

• This is the most clinically significant mimic because it frequently exhibits HCC-like imaging features rather than the classic targetoid appearance 3
• Shows non-rim arterial phase hyperenhancement (APHE) and non-peripheral washout—identical to HCC imaging hallmarks 3
• Contrasts with large duct iCCA, which displays the classic targetoid pattern with rim APHE and progressive central enhancement that would be categorized as LR-M 3
• The LR-M category (rim enhancement and/or early/marked washout) effectively captures large duct iCCA but misses small duct variants 4, 3

Combined Hepatocellular-Cholangiocarcinoma (cHCC-CCA)

• Exists on a continuous imaging spectrum that reflects its histologic dominance 3
• When HCC component predominates, can perfectly mimic pure HCC and meet LR-5 criteria 3
• Particularly problematic because core needle biopsies may sample only one component, leading to misclassification 3
• No reliable imaging features distinguish it from pure HCC when hepatocellular component dominates 5, 6

Benign Mimics

Inflammatory Hepatocellular Adenoma

• Can fulfill all LI-RADS v2018 criteria for LR-5 in cirrhotic patients 2
• Shows arterial phase hyperenhancement with washout on delayed imaging 2
• Particularly deceptive in alcoholic cirrhosis where adenomas are rare but can occur 2
• Requires immunohistochemistry (SAA and CRP expression, no aberrant β-catenin) for definitive diagnosis 2

Other Benign Lesions

• Focal nodular hyperplasia (FNH): Can show APHE, though typically maintains enhancement longer than HCC 4
• Hemangiomas: Atypical variants may show early enhancement patterns 7, 5
• Arterioportal shunts: Common pseudolesions on CT/MRI that can mimic true nodules, though rarely visualized on CEUS 4

Critical Diagnostic Pitfalls

Population Context Matters

The 98.5% positive predictive value for LR-5 applies only within well-defined target populations (cirrhosis, chronic hepatitis B) 1, 8. Outside these populations, vascular patterns are less specific and false positive risk increases substantially 8.

Size-Dependent Accuracy

• LR-5 criteria require lesions ≥1 cm 1
• Smaller lesions have higher rates of atypical presentations 6
• Approximately 40% of HCCs don't show classic imaging appearance 6

Practical Strategies to Minimize False Positives

When LR-5 Diagnosis is Uncertain:

1. Evaluate ancillary features beyond major criteria:

   • Presence of capsule appearance
   • Threshold growth (≥50% size increase in ≤6 months)
   • Mosaic architecture
   • Fat content in non-cirrhotic liver 8, 9

2. Use CEUS as second-line modality for indeterminate CT/MRI findings:

   • Real-time arterial phase evaluation prevents mistiming 4
   • Can upgrade LR-3/LR-4 lesions with few false positives 4
   • Eliminates arterioportal shunt pseudolesions 4

3. Integrate clinical context:

   • Tumor markers (AFP, CA19-9, PIVKA-II) 8, 3
   • Pattern of disease (multifocal vs. solitary)
   • Rate of growth
   • Patient demographics (inflammatory adenoma more common in young women, rare in cirrhotic men) 2

4. Consider biopsy when:

   • Patient is outside target population
   • Atypical features present (rim enhancement, marked/early washout suggesting LR-M)
   • Treatment decision would significantly change with histologic confirmation 8, 3

Common Caveat

Never rely solely on imaging in alcoholic cirrhosis patients with solitary lesions showing perfect LR-5 features—inflammatory adenoma, though rare, can be indistinguishable and requires different management 2. The combination of clinical improbability (adenoma in cirrhotic male) plus perfect imaging match for HCC usually justifies proceeding, but maintain diagnostic humility.