Pancreatic Cyst Fluid Analysis
When EUS-FNA is performed on a pancreatic cyst, the combined analysis of cyst fluid CEA (cutoff ≥192 ng/mL), cytology, and lipase levels provides the highest diagnostic accuracy for differentiating mucinous from non-mucinous cysts, though CEA cannot predict malignancy or high-grade dysplasia. 1, 2
Indications for EUS-FNA
EUS-FNA should only be performed when results will change clinical management and should be avoided if:
- The diagnosis is already established by cross-sectional imaging 1
- There is a clear indication for surgery 1
- The cyst-to-transducer distance is >10 mm 1
Perform EUS-FNA when:
- CT or MRI findings are unclear regarding cyst type 1
- Worrisome features are present (cyst ≥3 cm, main pancreatic duct 5-9 mm, mural nodules, thickened walls) 1, 3
- At least one worrisome feature exists in cysts ≥2.5 cm 1
Essential Cyst Fluid Tests and Their Diagnostic Yield
CEA Analysis (Primary Test)
CEA ≥192 ng/mL distinguishes mucinous from non-mucinous cysts with 52-78% sensitivity and 63-91% specificity 1, 2. This is the single most useful biochemical marker for cyst classification 2.
Critical limitation: CEA levels cannot differentiate benign mucinous cysts from those harboring high-grade dysplasia or invasive carcinoma 1, 2. CEA cannot predict malignant transformation 2.
Important pitfall: Lymphoepithelial cysts (benign lesions) can show markedly elevated CEA levels (>450 ng/mL), questioning the specificity for mucinous neoplasms 2.
Cytology
Cytology has 42% sensitivity but 99% specificity for differentiating mucinous from non-mucinous cysts 1. When combined with CEA, diagnostic accuracy improves significantly 1.
Target solid components or thickened cyst walls for cytology to detect high-grade dysplasia or cancer 1. Cytological evaluation detects approximately 30% more cancers than imaging features alone by identifying high-grade epithelial atypia 1.
Key limitation: Cytology often underestimates the degree of dysplasia due to sampling error and lesion heterogeneity 1. Inadequate cellularity is common, reducing diagnostic accuracy 1.
Amylase/Lipase
Amylase >250 U/L (or lipase elevation) suggests pseudocyst rather than neoplastic cyst 1. Amylase levels >479 U/L have 73% sensitivity and 90% specificity for detecting pseudocysts 4.
Molecular Analysis (Emerging)
KRAS/GNAS mutation analysis can differentiate IPMN or MCN from other cysts, though not yet standard management 1, 3. This testing is increasingly available and improves diagnostic accuracy when combined with CEA and cytology 2, 3.
Diagnostic Algorithm
If imaging shows high-risk stigmata (obstructive jaundice with cystic lesion, enhancing solid component, main pancreatic duct ≥10 mm): Proceed directly to surgery without EUS-FNA 1, 3
If worrisome features present but diagnosis unclear: Perform EUS-FNA with:
Interpretation:
Tests NOT Recommended
Brush cytology and forceps biopsy lack high-quality evidence and should not be performed 1.
Safety Considerations
EUS-FNA is safe with 3.4% complication rate (mostly mild) 1. Single-dose antibiotic prophylaxis is common practice, though evidence for benefit is limited 1, 3.
Relative contraindications:
Common Pitfalls to Avoid
- Do not rely on CEA alone to exclude malignancy—it only identifies mucinous cysts, not their malignant potential 2
- Do not perform EUS-FNA if surgery is already indicated based on imaging 1, 3
- Do not skip EUS-FNA in worrisome features without clear surgical indication—this misses opportunities to identify benign lesions that can be safely observed 3
- Do not send fluid for cytology alone when imaging shows no suspicious features—cytology yields no diagnostic benefit in this setting 5
Regulatory Note
Neither CEA nor amylase are FDA-approved for biomarker purposes in cyst fluid—these are off-label applications 2.