How to manage a hypodense liver lesion?

Management of Hypodense Liver Lesions

The management of a hypodense liver lesion depends critically on lesion size (≥1 cm vs <1 cm), patient risk factors (chronic liver disease, known malignancy, or normal liver), and the imaging modality on which it was discovered—with multiphase contrast-enhanced CT or MRI being the definitive next step for characterization in most scenarios. 1

Initial Risk Stratification

The first step is to categorize the patient into one of three clinical contexts, as this fundamentally determines the diagnostic pathway 1:

• Normal liver, no known malignancy: Benign lesions (hemangioma, cysts, focal nodular hyperplasia) are most likely, occurring in up to 15% of the general population 1
• Known chronic liver disease or cirrhosis: Hepatocellular carcinoma (HCC) becomes the primary concern, particularly for lesions ≥10 mm 1
• Known extrahepatic malignancy: Metastatic disease must be excluded, though benign lesions still occur in nearly 30% of cancer patients 1

Management Algorithm by Lesion Size and Clinical Context

Lesions >1 cm in Normal Liver (No Cirrhosis, No Known Malignancy)

For indeterminate lesions >1 cm discovered on ultrasound, noncontrast CT, or single-phase CT, proceed with either multiphase contrast-enhanced CT, MRI with and without IV contrast, or contrast-enhanced ultrasound (CEUS)—these are equivalent first-line options. 1

• Multiphase CT should include arterial and portal venous phases at minimum, with 2.5-5 mm slice thickness for optimal lesion characterization 1
• MRI with gadolinium differentiates between common benign lesions in 70% of cases, with hepatobiliary contrast agents (gadoxetate) providing additional diagnostic information 1, 2
• CEUS reaches a specific diagnosis in 83% of indeterminate lesions and distinguishes benign from malignant in 90% of cases, correctly characterizing 90% of hemangiomas and 90% of focal nodular hyperplasia 1

Lesions >1 cm in Patients with Known Malignancy

MRI with and without IV contrast or multiphase contrast-enhanced CT is appropriate, with FDG-PET/CT as an additional equivalent option when the lesion was initially found on noncontrast or single-phase imaging. 1

• The addition of PET/CT helps distinguish metastases from benign lesions in oncology patients 1
• For subcentimeter lesions that appear noncystic on grayscale ultrasound, CEUS correctly characterizes 95% of lesions overall and 98% of metastases 1
• Critical pitfall: Nearly one-third of hypoechoic masses in high-risk patients ≥46 years are malignant, warranting aggressive workup 3

Lesions >1 cm in Chronic Liver Disease/Cirrhosis

Follow the LI-RADS (Liver Imaging Reporting and Data System) algorithm using either MRI with and without IV contrast, multiphase contrast-enhanced CT, or CEUS—all are equivalent options. 1

• Triple-phase contrast CT (arterial, portal venous, delayed) is recommended per LI-RADS technical specifications 1
• Lesions ≥10 mm are required for definitive HCC diagnosis by imaging alone 1
• If AFP is elevated and the lesion is >2 cm in a cirrhotic liver, there is >95% probability of HCC, and further imaging is primarily for treatment planning rather than diagnosis 1
• Avoid biopsy if surgical resection is planned due to seeding risk 1

Lesions <1 cm

For lesions <1 cm in patients with known malignancy, MRI with and without IV contrast is the preferred modality. 1

For lesions <1 cm in chronic liver disease, either MRI with and without IV contrast or multiphase contrast-enhanced CT is appropriate. 1

• Subcentimeter lesions in low-risk patients (younger, no malignancy or liver disease) can receive conservative follow-up regardless of ultrasound features 3
• In cirrhotic patients, lesions <10 mm cannot be definitively diagnosed as HCC by imaging criteria and require surveillance 1

When Imaging Remains Indeterminate

If advanced imaging (MRI, multiphase CT, or CEUS) fails to provide a definitive diagnosis 2, 4:

• Fine needle aspiration or core biopsy may be required in doubtful cases 2
• Biopsy of non-tumor liver may be needed in non-cirrhotic patients to determine optimal surgical approach 1
• If uncertainty persists after biopsy, surgical resection is recommended to exclude malignancy 2

Common Diagnostic Pitfalls

• Arterial phase hyperenhancement occurs in both benign lesions (focal nodular hyperplasia, hepatocellular adenoma) and malignant lesions (HCC), requiring careful analysis of washout patterns and clinical context 4
• Hypointense lesions on T2-weighted MRI can represent a wide spectrum including focal nodular hyperplasia, hepatocellular adenoma, HCC, metastases, and granulomas—integration of all MRI sequences and clinical context is essential 5
• Age and risk status matter: Patients ≥61 years with high-risk status (malignancy or liver disease) have significantly decreased likelihood of benign lesions and warrant more aggressive evaluation 3
• Tc-99m sulfur colloid scans have no role in the modern evaluation of indeterminate liver lesions 1