Identification and Quantification of Malignant Cells in Cerebrospinal Fluid

Abstract

Usual diagnostic methods of leptomeningeal metastases (LM) in CerebroSpinal fluid (CSF), lack both specificity and sensitivity. The Veridex CellSearch® technique quantifying circulating tumour cells (CTCs) in blood was adapted to detect Tumour Cells (CSFTCs) in CSF from cancer patients with LM. CSF samples from 60 patients with established or suspected breast cancer or lung cancer LM and/or melanoma were evaluated. 5 mL CSF samples were collected on CellSave® preservative and analyzed within 3 days after CSF sampling. Gold Standard cytological analysis on 1 to 10 mL CSF samples from patients with established LM allowed sometimes the detection but usually not the quantification of TCs. In established LM, EpCAM+/cytokeratin+ or CD146+/HMW-MAA+ nucleated (DAPI+) cells were observed and enumerated with precision from one to up to 10 000 cells/mL. Their morphology on digital images galleries could be discriminant between breast and lung cancer. This methodology, established on a limited volume of CSF compared to the Gold Standard and allowing delayed processing, is of great interest in the diagnosis and follow-up of cancer patients with LM. The reliability of the method also opens new fields of investigation for other biological fluids and to precise the stem cell potential of metastatic cells in CSF.