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Pleural effusions occur as a consequence of either nonmalignant conditions (including congestive heart failure, pneumonia, pulmonary embolism, and liver cirrhosis) or malignant conditions (including lung, breast, and lymphoma cancers). Diagnosing the cause of an effusion can be difficult, requiring cytological examination of the fluid. Analysis of various tumor markers in pleural fluid has shown that these markers can differentiate between effusions caused by nonmalignant and malignant conditions and can enhance cytology findings.
Carbohydrate antigen 19-9 (CA 19-9) is a modified Lewis(a) blood group antigen. Healthy adults typically produce low to undetectable levels of CA 19-9. Serum concentrations of CA 19-9 may be elevated in patients with certain malignancies that secrete CA 19-9 into circulation, including cholangiocarcinoma, colorectal, stomach, bile duct, lung, ovarian, and pancreatic cancers.
Pleural fluid concentrations of CA 19-9 have been reported to be elevated in patients with certain malignancies. Malignancies that can secrete CA 19-9 and elevate serum CA 19-9 concentrations, including cholangiocarcinoma, colorectal, stomach, bile duct, lung, ovarian, and pancreatic cancers, typically also elevate CA 19-9 in pleural fluid. In contrast, malignancies that do not secrete CA 19-9, including mesothelioma, lymphoma, leukemia, and melanoma, have low concentrations of CA 19-9 in pleural fluid comparable to concentrations observed in nonmalignant effusions.
CA 19-9 results should be used in conjunction with cytological analysis of pleural fluid, imaging studies, and other clinical findings.
An adjuvant to cytology and imaging studies to differentiate between nonmalignant and malignant causes of pleural effusions
A pleural fluid carbohydrate antigen 19-9 (CA 19-9) concentration of > or =20.0 U/mL is suspicious, but not diagnostic, of a malignant source of the effusion. This cutoff yielded a sensitivity of 35%, specificity of 95%, and positive predictive value of 88% in a study of 200 patients presenting with effusion. CA 19-9 concentrations were significantly higher in effusions caused by CA 19-9-secreting malignancies, including cholangiocarcinoma, colorectal, stomach, bile duct, lung, ovarian, and pancreatic cancers. However, effusions caused by non-CA 19-9-secreting malignancies, including lymphoma, mesothelioma, leukemia, and melanoma, routinely had CA 19-9 concentrations <20.0 U/mL. Therefore, negative results should be interpreted with caution, especially in patients who have or are suspected of having a non-CA 19-9-secreting malignancy.
Correlation of all tumor marker results with cytology and imaging is highly recommended.
This test result should not be the sole basis for diagnosis. Carbohydrate antigen 19-9 (CA 19-9) is not specific for malignancy and testing has limited utility when used as the sole diagnostic test. Test results should be always correlated with cytology, imaging, and other clinical findings.
A low or negative CA 19-9 result (<20.0 U/mL) may be uninformative or misleading, as certain malignancies do not secrete CA 19-9 and will not produce elevated CA 19-9 concentrations in pleural effusions. Negative results should be interpreted with caution in patients who have or are suspected of having a non-CA 19-9-secreting malignancy or who have a cancer of unknown primary origin. Alternative methodologies, including cytology, imaging, and other tumor markers, are recommended instead.
Certain individuals (Lewis nonsecretors) do not produce the CA 19-9 antigen. A low or negative CA 19-9 result may, therefore, be uninformative or misleading in these individuals. Measuring serum CA 19-9 concentrations may be helpful to determine if the patient is a Lewis nonsecretor.
Serum CA 19-9 concentrations have been reported to be elevated as a consequence of certain nonmalignant conditions, including liver cirrhosis, pancreatitis, gallstones, and cholecystitis. It is unknown whether these conditions also cause CA 19-9 elevations in pleural fluid. Results should therefore be interpreted with caution in patients with these conditions.
An interpretive report will be provided.
1. Shitrit D, Zingerman B, Shitrit AB, et al: Diagnostic value of CYFRA 21-1, CEA, CA 19-9, CA 15-3, and CA 125 assays in pleural effusions: analysis of 116 cases and review of the literature. Oncologist 2005;10:501-507
2. Hackbarth JS, Murata K, Reilly W, Algeciras-Schimnich A: Performance of CEA and CA19-9 in identifying pleural effusions caused by specific malignancies. Clin Biochem 2010 Sep;43(13-14):1051-1055