What information should be included in a footnote for a pathology report for the Carbohydrate Antigen 19-9 (CA 19.9) test?

CA 19-9 Pathology Report Footnote

CA 19-9 is a tumor-associated antigen that is not tumor-specific and should be interpreted with caution in the context of clinical presentation and imaging findings, as it can be elevated in both malignant and benign conditions. 1

Test Definition and Methodology

• CA 19-9 (Carbohydrate Antigen 19-9) is a sialylated Lewis A blood group antigen commonly expressed and shed in pancreatic, hepatobiliary, and gastrointestinal diseases. 1
• Multiple commercial assay methods are available for quantitation; results from different testing methods cannot be directly compared or extrapolated. 1

Critical Limitations

Lewis Antigen-Negative Individuals

• 5-10% of the population are Lewis antigen-negative (Lewis a-b- genotype) and cannot produce CA 19-9, resulting in undetectable or very low levels (<1.0 U/mL) even in the presence of malignancy. 1, 2, 3
• Testing should not be attempted in this patient population. 1

False-Positive Elevations

• Benign biliary obstruction (regardless of etiology) can cause significantly elevated CA 19-9 levels. 1
• Cholangitis and biliary infections frequently elevate CA 19-9 levels. 1
• Other benign conditions associated with elevated CA 19-9 include: 1, 4
  • Chronic pancreatitis and autoimmune pancreatitis 1, 5
  • Inflammatory hepatobiliary conditions 1
  • Thyroid disease 1
  • Pneumonia, pleural effusion, renal failure 4
• CA 19-9 levels should be measured after complete biliary decompression when evaluating for pancreatic pathology. 1

Malignant Conditions

• Elevated in multiple malignancies beyond pancreatic cancer, including: 1
  • Colorectal cancer
  • Hepatocellular carcinoma
  • Ovarian cancer
  • Gastric and other upper gastrointestinal tract tumors
  • Cholangiocarcinoma
  • Lung cancer 4

Clinical Interpretation

Not Recommended For:

• Screening asymptomatic populations (positive predictive value 0.5-0.9%) 1, 2, 3
• Sole determinant of operability or resectability 1
• Definitive evidence of disease recurrence without imaging confirmation 1

Appropriate Clinical Uses:

• Diagnostic aid in symptomatic patients (sensitivity 79-81%, specificity 82-90%) when combined with imaging findings 1, 2, 3
• Prognostic information: Normal levels (<37 U/mL) associated with better outcomes; levels >100-180 U/mL may suggest advanced or unresectable disease 1, 2, 3
• Monitoring treatment response: Serial measurements during active treatment for advanced disease (every 1-3 months); rising levels may indicate progressive disease requiring imaging confirmation 1
• Post-operative surveillance: Normalization or ≥20-50% decrease from baseline correlates with improved survival 2, 3

Important Clinical Caveats

• Elevated CA 19-9 alone does not establish a diagnosis of malignancy and must be correlated with clinical presentation, imaging studies, and/or tissue diagnosis. 1, 4
• Levels can be transiently elevated following recent vaccination (including COVID-19) or acute inflammatory conditions. 5
• In primary sclerosing cholangitis, a cut-off of 129-130 U/mL provides optimal sensitivity (78-79%) and specificity (98%) for cholangiocarcinoma detection. 1

Reference Range: <37 U/mL 1, 2, 3