What conditions can elevate Carbohydrate Antigen 19-9 (CA19-9) levels?

Conditions That Can Elevate CA 19-9 Levels

CA 19-9 can be elevated in multiple malignant and benign conditions, with pancreatic adenocarcinoma, cholangiocarcinoma, and biliary obstruction being the most common causes. 1

Malignant Conditions

• Pancreatic adenocarcinoma - CA 19-9 is elevated in up to 85% of patients with pancreatic cancer 1
• Cholangiocarcinoma (bile duct cancer) - elevated in up to 85% of patients 1
• Other gastrointestinal malignancies:
  • Colorectal cancer 1, 2
  • Gastric cancer 2
  • Hepatocellular carcinoma 1, 2
• Non-GI malignancies:
  • Ovarian cancer 1, 2
  • Lung cancer 2

Benign Conditions

• Biliary obstruction - a major cause of false-positive CA 19-9 results (10-60% of cases) 1, 3
• Inflammatory conditions of the hepatobiliary system:
  • Cholangitis 1
  • Choledocholithiasis (bile duct stones) 1, 2
  • Cholecystitis 2
• Pancreatitis (acute and chronic) 1, 4
• Autoimmune pancreatitis - can present with elevated CA 19-9, mimicking pancreatic cancer 1
• Liver diseases:
  • Hepatitis 4
  • Cirrhosis 2
• Other inflammatory conditions:
  • Pneumonia 2
  • Pleural effusion 2
  • Systemic lupus erythematosus (SLE) 2
• Renal failure 2
• Thyroid disease 1

Important Clinical Considerations

• CA 19-9 is not tumor-specific and should not be used alone for diagnosis 1
• Approximately 5-10% of the population is Lewis antigen negative and cannot produce CA 19-9, making testing ineffective in these individuals 1, 5
• CA 19-9 levels correlate with:
  • Liver function tests - alkaline phosphatase, ALT, AST, bilirubin, GGT 4
  • Other tumor markers like CEA 4
• CA 19-9 levels are typically significantly higher in malignant conditions than in benign ones 4, 2
• In pancreatic cancer, CA 19-9 levels correlate with:
  • Tumor stage 6
  • Tumor location (highest in body of pancreas) 6
  • Resectability (levels >100 U/mL suggest unresectable disease) 6, 3
  • Presence of liver metastases 6

Diagnostic Approach to Elevated CA 19-9

• CA 19-9 should not be used as a screening test for pancreatic cancer due to inadequate sensitivity and specificity 1, 5
• Interpretation of elevated CA 19-9 must be made in light of the clinical condition 4, 2
• Combination with other tumor markers (CEA, CA-125) may improve diagnostic accuracy 1
• Abdominopelvic CT has excellent sensitivity (94.1%) for detecting malignancies causing elevated CA 19-9 7
• Persistently elevated CA 19-9 after biliary decompression strongly suggests malignancy 1

Pitfalls to Avoid

• Do not use CA 19-9 as a screening test in asymptomatic individuals 1, 5
• Do not rely solely on CA 19-9 for diagnosis without confirmatory imaging or biopsy 1
• Be aware that jaundice can cause false-positive CA 19-9 elevations; levels should be measured after biliary decompression when possible 1, 3
• Do not attempt CA 19-9 testing in Lewis-negative individuals (5-10% of population) 1, 5
• Remember that small pancreatic tumors may not cause CA 19-9 elevation 1