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An adjunct to cytology to differentiate between malignancy-related ascites and benign causes of ascites formation
Malignancy accounts for approximately 7% of cases of ascites formation. Malignant disease can cause ascites by various mechanisms including: peritoneal carcinomatosis (53%), massive liver metastasis causing portal hypertension (13%), peritoneal carcinomatosis plus massive liver metastasis (13%), hepatocellular carcinoma plus cirrhosis (7%), and chylous ascites due to lymphoma (7%). The evaluation and diagnosis of malignancy-related ascites is based on the patient clinical history, ascites fluid analysis, and imaging tests.
The overall sensitivity of cytology for the detection of malignancy-related ascites ranges from 58% to 75%. Cytology examination is most successful in patients with ascites related to peritoneal carcinomatosis as viable malignant cells are exfoliated into the ascitic fluid. However, only approximately 53% of patients with malignancy-related ascites have peritoneal carcinomatosis. Patients with other causes of malignancy-related ascites almost always have a negative cytology.
Carbohydrate antigen 19-9 (CA 19-9) is a modified Lewis(a) blood group antigen. CA 19-9 may be elevated in the serum patients with gastrointestinal malignancies such as cholangiocarcinoma, pancreatic cancer, or colon cancer. Measurement of CA 19-9 in ascitic fluid is sometimes used in combination with cytology for detecting malignancy-related ascites.
An interpretive report will be provided.
A peritoneal fluid carbohydrate antigen 19-9 (CA 19-9) concentration >32 U/mL is suspicious, but not diagnostic, of a malignancy-related ascites. This clinical decision limit cutoff yielded 44% sensitivity and 93% specificity in a study of 137 patients presenting with ascites. However, ascites caused by malignancies not associated with increase serum CA 19-9 concentrations, including lymphoma, mesothelioma, leukemia, and melanoma, routinely had CA 19-9 concentrations <32 U/mL. Therefore, negative results should be interpreted with caution, especially in patients who have or are suspected of having a malignancy not associated with elevated CA 19-9 levels in serum.
Do not use peritoneal fluid carbohydrate antigen 19-9 (CA 19-9) levels concentration as absolute evidence of the presence or the absence of malignant disease. The CA 19-9 result should be interpreted in conjunction with information from the clinical evaluation of the patient and other diagnostic procedures.
Approximately 10% of the Caucasian population does not express CA 19-9 due to the deficiency of a fucosyltransferase enzyme. Consequently, low values in these individuals are not informative regarding malignancy-related ascites.
Immunometric assays can, in rare occasions, be subject to interferences such as "hooking" at very high analyte concentrations (false-low results) and heterophilic antibody interference (false-high results). If the clinical picture does not fit the laboratory result, these possibilities should be considered.
CA 19-9 values are method-dependent; therefore, the same method should be used to serially monitor patients.
An in-house study was performed to select a clinical decision limit to differentiate between malignancy-related benign causes of ascites with high specificity. The study included 83 cases of benign ascites and 54 cases of malignancy-related ascites. Within the malignancy-related ascites, there were 9 specimens with malignancies known not to secrete carbohydrate antigen 19-9 (CA 19-9) in serum (lymphoma, leukemia, melanoma, sarcoma, and neuroendocrine tumors). Amongst the group that are known to secrete CA 19-9 in serum (n=45), there were the following malignancies: pancreatic, breast, gastric, colon, bladder, cholangiocarcinoma, gynecological cancers, peritoneal carcinomatosis, and hepatocellular carcinoma. Using a clinical decision limit cutoff of >32 U/mL, the specificity was 93% for the benign ascites group. The sensitivity was 49% for those malignancies associated with elevated CA 19-9 in serum.
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2. Sari R, Yildirim B, Sevinc A, et al: The importance of serum and ascites fluid alpha-fetoprotein, carcinoembryonic antigen, CA 19-9, and CA 15-3 levels in differential diagnosis of ascites etiology. Hepatogastroenterology 2001 Nov-Dec;48(42):1616-1621