Intrathecal synthesis of tumor markers is a highly sensitive test in the diagnosis of leptomeningeal metastasis from solid cancers

Abstract

Identification of neoplastic cells in cerebrospinal fluid (CSF) by cytological analysis is the key diagnostic feature of leptomeningeal metastasis (LM). Because of the lack of sensitivity of this test, considerable efforts have been made to identify alternative diagnostic markers. Data from the literature suggest that measurement of tumor markers (TM) in CSF may be helpful for improving the diagnosis. We analyzed the concentrations of the TM carcinoembryonic antigen (CEA), CA15.3, CA125 and CA19.9 in both CSF and serum from 18 patients with neoplastic meningitis diagnosed by CSF cytology. We also performed these same measurements in 50 patients affected by other neurological diseases (OND) in order to evaluate putative intrathecal synthesis. In addition, CSF and serum concentrations of the proangiogenic factor VEGF (vascular endothelial growth factor) were evaluated. All LM patients showed intrathecal synthesis for at least one TM. In one patient, a negative CSF cytology after treatment paralleled normalization of tumor marker synthesis. None of the OND patients displayed intrathecal TM synthesis. The VEGF Index (CSF/serum VEGF relative to CSF/serum albumin ratios) was significantly higher in LM patients compared with the control group. However, significant overlap between LM patients and values seen in those with OND was observed. Evaluation of intrathecal TM synthesis is a specific, sensitive, reliable, and reproducible diagnostic tool, and is useful to support diagnosis of carcinomatous meningitis.