Detection of cancer cells in the cerebrospinal fluid: current methods and future directions

Abstract

The spread of cancer into the central nervous system is a serious problem leading to neurological symptoms and rapid mortality. The current tools available for detecting the spread of cancer into the cerebrospinal fluid (CSF) are cytology, neurologic examination, and neuroimaging. All three of these methods can be applied in concert to reach a diagnosis, but they all suffer from a lack of sensitivity, leading to delays in treatment in many cases. An overview of research tools in the field of CSF cancer detection reveals a variety of promising technologies that can be used to answer questions about the biology of metastatic cancer and to develop more powerful clinical detection methods. Methods currently under investigation include new immunocytochemistry methods and flow cytometry for the in vitro detection of cells. Additionally, polymerase chain reaction, fluorescence in situ hybridization, capillary electrophoresis with laser-induced fluorescence, and mass spectrometry using matrix-assisted laser absorption-deionization time-of-flight and surface-enhanced laser desorption/ionization time-of-flight techniques are being tested for in vitro assessment of the non-cellular biomarkers in CSF. For in vivo detection of cancer in the CSF, research techniques include certain quantum dot platforms as well as magnetic iron oxide nanoparticles. As systemic therapies for cancer improve, the CNS is becoming a more common site of disease recurrence. This increases the importance of effective detection methods in the CSF, since early intervention can maximize therapeutic benefit. Furthermore, many cell-based detection methods can be combined with therapeutic agents to serve multiple medical functions through a common targeting system.

Assisting the neurologist in diagnosis of CNS malignancies ‐ Current Possibilities and Limits of Cerebrospinal Fluid Cytology and Immunocytochemistry

“…In hematology (30% of all malignancies in the CSF) flow cytometry has been confirmed as a method of choice superior to immunocytopathology by many studies (Chamberlain et al., 2009; Chandra et al., 2009; Kaplan et al., 1990; Weston et al., 2011). Nevertheless, it faces frequently the same problem of sample volume.…”

“…Nevertheless, identification of the neoplastic cells is only partly achievable with cytomorphology and histochemical stainings (Glantz et al., 1998; Kaplan et al., 1990; Twijnstra et al., 1987; Wasserstrom et al., 1982). Ancillary techniques are now a part of guidelines and even routine investigations (Chamberlain et al., 2009; Chandra et al., 2009; Coakham et al., 1984; Weston et al., 2011). …”

Targeting cerebrospinal fluid for discovery of brain cancer biomarkers

“…medulloblastoma, primitive neuroectodermal tumors, germ cell tumors, ependymoma, and glioma may be disseminated throughout the neuroaxis by the flow of the CSF. [12][13][14] Table 1 shows the particular incidence of malignant leptomeningeal involvement in selected primary brain cancers. Currently microscopic evaluation of CSF is routinely performed in CNS malignancies with frequent leptomeningeal spread, such as medulloblastomas, PNET, pineoblastomas, germcell tumors and CNS lymphoma.…”

“…[15] Cancer therapy and prognosis of these groups of brain cancer are crucially determined by positive CSF cytology. [13,14] CSF cytoanalysis CSF cytology, in which CSF is prepared and examined under a microscope to look for cells, is currently considered the gold standard for diagnosis of brain cancer with leptomeningeal spread and metastatic cancer to the brain. [14] To achieve CSF cytology a sample can be obtained at the time of tumor surgery or by lumbar or intracerebroventricular (ICV) reservoir puncture.…”

“…[13,14] CSF cytoanalysis CSF cytology, in which CSF is prepared and examined under a microscope to look for cells, is currently considered the gold standard for diagnosis of brain cancer with leptomeningeal spread and metastatic cancer to the brain. [14] To achieve CSF cytology a sample can be obtained at the time of tumor surgery or by lumbar or intracerebroventricular (ICV) reservoir puncture. [3] However, lumbar CSF remains the specimen of choice to detect malignant cells of primary CNS tumors.…”