Novel method for the detection and quantification of malignant cells in the CSF of patients with leptomeningeal metastasis of lung cancer

The aim of the present study was to discuss a novel method for the detection of malignant tumor cells in cerebrospinal fluid (CSF), by observing tumor marker-immunostaining fluorescence in situ hybridization (TM-iFISH) enrichment and by counting CSF malignant tumor cells in patients with lung cancer leptomeningeal metastasis (LM). A total of 10 CSF samples were collected from 6 patients that presented with lung cancer LM. For each patient, 20 ml CSF was obtained through a lumbar puncture, of which 7.5 ml was used to count the number of malignant tumor cells in the CSF using TM-iFISH enrichment. Cytological and biochemical examinations were conducted on the remaining 10 ml and 2.5 ml CSF, respectively. The 10 CSF samples were successfully analyzed by TM-iFISH, and the tumor cell count range was 3-1,823 cells/7.5 ml CSF in 7 of the samples detected. There were no tumor cells detected in the remaining 3 samples. Tumor cells were revealed in 3 of the samples through the CSF cytological examinations, and albumin protein levels were indicated to be greater than the normal range (normal range, 0.15-0.45 g/l), in 9 of the samples using CSF biochemical examinations. Additionally, TM-iFISH was performed again to count the CSF malignant tumor cells in 3 of the patients following intrathecal injection of chemotherapy (methotrexate 10 mg and dexamethasone 5 mg). The results indicated that the malignant tumor cell count of 2 of the patients had decreased in comparison to the pre-treatment cell count. As it is capable of enriching and counting CSF malignant tumor cells in patients with lung cancer LM, TM-iFISH may be an effective method to diagnose lung cancer LM and to evaluate its efficacy.