Is a 4 mm side branch intraductal mucinous neoplasia (SB-IPMN) of the pancreas with an elevated Carbohydrate Antigen 19-9 (CA 19-9) level of 140 indicative of malignancy?

Risk Assessment of a 4 mm Side Branch IPMN with Elevated CA 19-9

A 4 mm side branch intraductal papillary mucinous neoplasm (SB-IPMN) with an elevated CA 19-9 of 140 U/mL represents a concerning combination that requires careful evaluation, but is not definitively malignant based on current evidence. This case presents with one small-sized lesion but with a significantly elevated tumor marker.

Risk Stratification of This Case

Concerning Features Present:

• Elevated CA 19-9 (140 U/mL): This is significantly above the 37 U/mL threshold and represents a relative indication for surgery according to European guidelines 1, 2
• CA 19-9 values >37 U/mL have been associated with a positive predictive value of 74.0% and accuracy of 81.7% for identifying invasive IPMN 1

Reassuring Features:

• Small cyst size (4 mm): Well below the 40 mm threshold that would independently raise concern 1
• Side branch involvement only: Branch duct IPMNs generally have lower malignancy rates (6-46%) compared to main duct IPMNs (57-92%) 3
• No reported mural nodules: The absence of enhancing mural nodules ≥5 mm (which would be an absolute indication for surgery) 1
• No reported main pancreatic duct dilation: Another high-risk feature if absent

Diagnostic Algorithm

1. Confirm CA 19-9 elevation:

   • Repeat the CA 19-9 measurement to confirm the elevation 2
   • Consider potential non-malignant causes of CA 19-9 elevation (biliary obstruction, inflammation) 2

2. Complete imaging workup:

   • MRI with MRCP is the gold standard for evaluating IPMN features 1, 2
   • Endoscopic ultrasound (EUS) to assess for:
     • Mural nodules (especially those ≥5 mm)
     • Main pancreatic duct involvement
     • Solid components
     • Wall thickening

3. Laboratory evaluation:

   • Liver function tests to rule out biliary obstruction
   • Pancreatic enzymes to assess for pancreatitis
   • Fasting glucose/HbA1c to check for new-onset diabetes 2

4. Consider EUS-guided FNA:

   • For cytology and cyst fluid analysis if other concerning features are found
   • Positive cytology would be an absolute indication for surgery 1

Management Recommendation

Based on the European guidelines for pancreatic cystic neoplasms 1:

1. This case presents with one relative indication for surgery (elevated CA 19-9) but the very small size (4 mm) is reassuring.

2. Decision algorithm:

   • If additional concerning features are found on further workup (mural nodules, MPD dilation, positive cytology), proceed to surgical evaluation
   • If no additional concerning features are found, close surveillance is appropriate

3. Surveillance protocol:

   • MRI with MRCP every 6 months for the first year
   • If stable, annual imaging thereafter
   • Regular CA 19-9 monitoring
   • Immediate re-evaluation if symptoms develop (new-onset diabetes, pancreatitis)

Important Caveats

• CA 19-9 can be elevated in non-malignant conditions including biliary obstruction and inflammation 2
• Approximately 5-10% of the population cannot produce CA 19-9 (Lewis antigen-negative) 2
• Small IPMNs can still develop high-grade dysplasia or cancer, highlighting the importance of evaluating for multiple risk factors 1
• The risk of IPMN progression increases over time, so continued surveillance is necessary even if initial evaluation is reassuring 1

The presence of an elevated CA 19-9 in the context of even a small SB-IPMN warrants thorough evaluation and close follow-up, but does not automatically indicate malignancy without other high-risk features.