What bloodwork should be ordered for a patient with complex and simple hepatic (liver) cysts?

Bloodwork for Hepatic Cysts

Routine bloodwork is generally not indicated for simple hepatic cysts, but when complex features are present, serum tumor markers (CEA and CA19-9) should NOT be ordered as they cannot reliably distinguish benign cysts from malignant lesions. 1

For Simple Hepatic Cysts

• No bloodwork is required for asymptomatic simple hepatic cysts, as these are benign developmental anomalies that do not require laboratory monitoring or follow-up. 1

• Simple cysts are diagnosed by imaging characteristics alone (anechoic on ultrasound with posterior acoustic enhancement and no internal echoes). 2, 3

For Complex Hepatic Cysts

When cysts demonstrate complex features (irregular walls, septations, thick walls, or atypical content), the diagnostic approach focuses on imaging rather than bloodwork. 1

Why Tumor Markers Are Not Helpful

• Serum CA19-9 and CEA cannot discriminate between simple hepatic cysts and mucinous cystic neoplasms (MCNs) with adequate accuracy. 1

• CA19-9 is elevated in up to 50% of patients with simple hepatic cysts or polycystic liver disease, making it non-specific. 1

• Serum CEA remains normal in simple cysts but is elevated in only 49% of cystadenomas and 75% of cystadenocarcinomas, with poor discriminatory ability (AUC 0.69). 1

• The 2022 EASL guidelines explicitly state with 100% consensus that CEA and CA19-9 in blood cannot be used to differentiate between hepatic cysts and MCNs. 1

When Cyst Infection Is Suspected

If clinical features suggest infected hepatic cyst (fever, abdominal pain, elevated inflammatory markers):

• Complete blood count to assess for leukocytosis (>11,000/L suggests infection). 4

• C-reactive protein (CRP) as an inflammatory marker. 4

• Blood cultures if systemic infection is suspected. 1

• Consider cyst aspiration for culture and neutrophil debris analysis, which provides definitive diagnosis. 1

When Polycystic Liver Disease Is Present

If multiple cysts (>10-20 cysts) suggest polycystic liver disease:

• Renal function tests (creatinine, BUN) to screen for associated autosomal dominant polycystic kidney disease (ADPKD), which occurs in 70-90% of PLD cases. 4

• Liver function tests are not routinely indicated unless there is concern for biliary compression or advanced disease. 4

• Genetic testing is rarely performed as it does not change management. 5

Critical Pitfalls to Avoid

• Do not order CA19-9 or CEA to "rule out" malignancy in complex cysts—these markers lack sufficient sensitivity and specificity. 1

• Do not rely on elevated CA19-9 alone to diagnose malignancy, as it correlates with total cyst volume in benign disease. 1

• Complex cysts require MRI with contrast-enhanced sequences for definitive characterization, not bloodwork. 1, 4

• If cyst fluid is obtained (via aspiration), TAG-72 (CA72-4) in cyst fluid may help distinguish simple cysts from MCNs (sensitivity 79%, specificity 97%), but this requires invasive sampling. 1

Summary Algorithm

1. Simple cyst on imaging → No bloodwork needed 1
2. Complex cyst features → MRI for characterization (not tumor markers) 1
3. Suspected infection → CBC, CRP, blood cultures 1, 4
4. Multiple cysts (PLD) → Renal function tests to screen for ADPKD 4, 5
5. Worrisome features for malignancy → Surgical resection for definitive diagnosis, not serum markers 1