Modern cerebrospinal fluid analyses for the diagnosis of diffuse large B-cell lymphoma of the CNS

Abstract

CNS lymphomas represent rare and aggressive variants of extranodal non-Hodgkin's lymphomas, which may present with diverse neurological symptoms and are often diagnostically challenging. Primary CNS lymphomas develop within the CNS and characteristically involve the brain, leptomeninges, eyes and, in rare cases, spinal cord. Secondary CNS lymphomas are characterized by expansion of systemic lymphomas to the CNS. Multimodal investigation of cerebrospinal fluid (CSF) comprises an important component of the diagnostic work-up for patients with suspected CNS lymphomas. Cytopathological examination of the CSF is still regarded as the 'gold standard' for the diagnosis of leptomeningeal malignant disease. However, cytopathology has only a low sensitivity in detecting leptomeningeal lymphoma involvement. Modern technologies including proteochemical and immunophenotypic studies by flow cytometry, and molecular genetic analyses of CSF may increase sensitivity and specificity, therefore, facilitating the diagnosis of CNS lymphomas. This review gives an overview and discussion of the current aspects of CSF analyses in CNS lymphomas.

Case Report: Concurrent primary CNS lymphoma and meningothelial meningioma - nuances of diagnosis and management

“…This is because PCNSL is particularly chemo-and radiosensitive. Conversely, gross total resection is the gold standard in the management of meningiomas and gliomas (Baraniskin & Schroers, 2014;Gordon et al, 2011;Hoang-Xuan et al, 2015;Korfel & Schlegel, 2013;Muñiz et al, 2014). The same principle applies for steroid administration.…”

“…Interestingly in our case, the initiation of high-dose dexamethasone did not affect our diagnosis. The typical diagnostic workup for CNS lymphoma consists of CSF analysis for markers such as IL-10, CXCL13, CD19, CD20 or flow cytometry (Baraniskin et al, 2011;Baraniskin & Schroers, 2014;Muñiz et al, 2014;Rubenstein et al, 2013). Due to the mass effect that is exerted by meningiomas, CSF analysis is difficult without a craniotomy as a lumbar puncture would not be recommended in such a setting.…”

Tumor-Associated CSF MicroRNAs for the Prediction and Evaluation of CNS Malignancies

“…CSF cytology, in which CSF is examined under a microscope to look for neoplastic cells (presence or absence) is currently considered the gold standard test for diagnosis, tumor staging, and therapy decisions in many types of cancer such as medulloblastoma, lymphoma, and metastatic carcinomas [ 65 ]. Although indispensable, this method bears neither quantification nor molecular analysis of tumor cells, lacks sensitivity and assignment to a particular tumor is often not possible [ 65 , 66 , 67 ].…”

“…To maximize the chances of finding brain cancer markers in the CSF, it has been realized that it is necessary to detect changes at the molecular level rather than waiting for a macroscopic tumor to emerge [ 65 ]. Various methods and new technologies are being tested for in vitro assessment of CSF looking for potential markers for CNS cancers including: proteochemical and immunophenotypic studies by flow cytometry (that provides information about cell surface protein expression), molecular genetic analyses of CSF [ 67 ], immunocytochemistry, immunoglobulin heavy chain (IgH) rearrangement which analyzes the clonality of the antibodies being produced, polymerase chain reaction, fluorescence in-situ hybridization (FISH), DNA single cell cytometry, capillary electrophoresis and mass spectrometry reviewed in [ 4 , 65 ]. Proteomic profiling of CNS malignancies has revealed that free immunoglobulin light chains and antithrombin III, a serine protease inhibitor that is associated with neo-vascularization, are differentially expressed in some brain cancers [ 68 , 69 ].…”

“…The group identified specific miRNAs that are expressed with significant levels in the CSF of patients with PCNSL compared to control. Using candidate approach and miRNA quantification by qRT-PCR, the group discovered that miR-19, miR-21, and miR-92a in CSF accurately discriminates patients with primary central nervous system lymphoma from other neurologic disorders controls, indicating significant diagnostic value and increased diagnostic accuracy with 95.7% sensitivity and 96.7% specificity [ 25 , 62 , 67 ]. On the same theme, Scott et al conducted a review of the literature on CNS lymphoma diagnosis (1966 to October 2011) and extracted data regarding the usefulness of CSF cytology in the diagnosis of CNS lymphoma.…”