Diagnostic Workup for Multiple Liver, Kidney, and Testicular Cysts
The combination of multiple liver cysts and kidney cysts most strongly suggests Autosomal Dominant Polycystic Kidney Disease (ADPKD) with polycystic liver disease, which affects 70-90% of ADPKD patients and represents the most common genetic cause of this presentation. 1
Immediate Diagnostic Steps
Family History Assessment
- Obtain detailed three-generation family history of kidney disease, dialysis, transplantation, or early death from kidney failure. 2 If family history is positive for ADPKD, this significantly simplifies the diagnostic pathway and may allow for targeted genetic testing of known familial variants. 2
Imaging Protocol
Order MRI of the abdomen (kidneys and liver) with T1-weighted, T2-weighted, and contrast-enhanced sequences as the definitive diagnostic test. 2, 1 MRI is superior to ultrasound and CT for detecting small cysts, particularly in patients with renal insufficiency. 2, 1
Key MRI Findings to Assess:
- Total number of kidney cysts: ADPKD diagnosis requires ≥3 total kidney cysts (ages 15-39), ≥2 cysts in each kidney (ages 40-59), or ≥4 cysts in each kidney (age ≥60). 2
- MRI-specific criteria (ages 16-40): >10 total kidney cysts confirms ADPKD; <5 total cysts rules it out. 2
- Liver cyst count: Polycystic liver disease is defined as >10 hepatic cysts. 2, 1
- Cyst characteristics: Simple cysts show high T2 signal and low T1 signal; complicated cysts may show hemorrhage, infection, septations, or wall thickening. 2, 1
- Bile duct evaluation: Look for the "central dot sign" (fibrovascular bundles within dilated cystic ducts) which is pathognomonic for Caroli syndrome, an alternative diagnosis featuring congenital liver fibrosis and kidney cysts. 2, 1
Laboratory Testing
Check basic metabolic panel, serum creatinine, and estimated GFR to assess kidney function. 2 People with ADPKD may have preserved kidney function despite multiple cysts, but baseline assessment is essential for prognostication. 2
Do not order tumor markers (CEA, CA19-9) as they cannot reliably distinguish benign from malignant cystic lesions. 3, 4
If fever, flank pain, or systemic symptoms are present: Check CBC (looking for WBC >11 × 10⁹/L) and C-reactive protein (looking for CRP ≥50 mg/L) to evaluate for infected kidney cyst. 2
Genetic Testing Indications
Proceed with genetic testing (PKD1, PKD2, and minor gene panel) if any of the following apply: 2
- Imaging findings are equivocal or atypical
- No family history of ADPKD but multiple cysts present
- Age <30 years and considering living kidney donation
- Discordant imaging and kidney function (e.g., many cysts but normal GFR or vice versa)
- Very early onset or unusually severe disease
- Family planning or preimplantation diagnosis requested
Genetic testing is particularly valuable because PKD1 mutations cause more severe disease than PKD2 mutations, and truncating mutations are worse than non-truncating mutations. 2 This information guides prognosis and treatment decisions.
Testicular Cyst Consideration
The testicular cyst is likely incidental and unrelated to ADPKD, as testicular cysts are not a recognized extrarenal manifestation of polycystic kidney disease. 2, 5 However, if the testicular cyst is symptomatic or has concerning features on imaging, refer to urology for independent evaluation with scrotal ultrasound. The testicular finding should not distract from the primary diagnostic focus on ADPKD.
Alternative Diagnoses to Exclude
Caroli Syndrome
If MRI shows intrahepatic bile duct dilatations rather than discrete round cysts, order MRCP (magnetic resonance cholangiopancreatography) which has the highest diagnostic accuracy for Caroli syndrome. 2, 1, 3 Caroli syndrome presents with segmental intrahepatic saccular or fusiform cystic areas and the pathognomonic central dot sign. 2, 1
Infectious Etiologies
If there is travel history to endemic areas (Eastern Europe, Middle East, North Africa, East/Southeast Asia), order echinococcal serology and liver fluke serology. 1 Echinococcus granulosus causes cystic echinococcosis affecting liver (70%) with possible concurrent renal involvement. 1 However, this is unlikely if cysts are present in both organs symmetrically.
Critical Diagnostic Pitfall
Do not assume liver lesions are truly "cysts" without proper MRI characterization—complex hepatic cysts with hemorrhage, infection, or thick walls can mimic solid lesions or granulomas on suboptimal imaging. 1, 4 If initial imaging described "granulomas" or "masses," these may actually be complicated hepatic cysts that appear complex due to hemorrhagic or proteinaceous content. 2, 1
Follow-Up Imaging Strategy
If ADPKD is confirmed and cysts are uncomplicated, no routine repeat imaging is required for the cysts themselves. 2, 3 However, annual blood pressure monitoring and kidney function assessment (serum creatinine, eGFR) are mandatory. 2, 5
Screen for intracranial aneurysms with MR angiography if there is family history of intracranial aneurysm or subarachnoid hemorrhage, personal history of prior aneurysm rupture, high-risk occupation (pilot, etc.), or patient anxiety about rupture risk. 5
Use Mayo Imaging Classification (total kidney volume measurements) to predict future kidney function decline and timing of kidney failure, which guides decisions about disease-modifying therapy with tolvaptan. 2, 5