Liquid biopsy for Primary Central Nervous System Lymphoma Diagnosis
Some preliminary studies have explored the feasibility of liquid biopsy for PCNSL diagnosis. These studies have investigated the presence of tumor-specific genetic alterations or biomarkers in the CSF or blood of PCNSL patients. For example, the detection of specific gene rearrangements, such as MYD88 or IGH gene rearrangements, in the CSF or blood samples has shown promise in aiding PCNSL diagnosis.
While these initial findings are promising, further research is needed to establish the reliability, sensitivity, and specificity of liquid biopsy in PCNSL diagnosis. The challenges in applying liquid biopsy to PCNSL include the relatively low levels of circulating tumor components in the bloodstream and the potential for false negatives due to the heterogeneous nature of the disease.
In summary, while liquid biopsy holds potential as a non-invasive diagnostic tool for various cancers, its application for PCNSL diagnosis is still in the early stages of investigation. The current standard diagnostic methods, including brain imaging, CSF analysis, and brain biopsy, remain the primary approaches for diagnosing PCNSL. Consultation with a healthcare professional specializing in oncology and neurology is essential for accurate diagnosis and appropriate treatment planning.
In the last years genome analyses using liquid biopsy specimens have progressed and are becoming popular in the management of PCNSL, thereby enabling neurosurgeons to avoid invasive brain biopsy. 1).
CSF
Diagnosing central nervous system (CNS) lymphoma remains a challenge. Most patients have to undergo brain biopsy to obtain tissue for diagnosis, with associated risks of serious complications. Diagnostic markers in blood or cerebrospinal fluid (CSF) could facilitate early diagnosis with low complication rates.
van Westrhenen et al., performed a systematic review literature search for studies on markers in blood or cerebrospinal fluid for the diagnosis CNS lymphoma and assessed the methodological quality of studies with the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2).
They evaluated diagnostic value of the markers at a given threshold, as well as differences between mean or median levels in patients versus control groups. Twenty-five studies were included, reporting diagnostic value for 18 markers in CSF (microRNAs -21, -19b, and -92a, RNU2-1f, CXCL13, interleukins -6, -8, and -10, soluble interleukin-2-receptor, soluble CD19, soluble CD27, tumour necrosis factor-alfa, beta-2-microglobulin, antithrombin III, soluble transmembrane activator and calcium modulator and cyclophilin ligand interactor, soluble B cell maturation antigen, neopterin and osteopontin) and three markers in blood (microRNA-21 soluble CD27, and beta-2-microglobulin). All studies were at considerable risk of bias and there were concerns regarding the applicability of 15 studies. CXCL13, beta 2 microglobulin and neopterin have the highest potential in diagnosing CNS lymphoma, but further study is still needed before they can be used in clinical practice 2).
Flow cytometry
Flow cytometry has a high specificity and can confirm the diagnosis of a lymphoma significantly faster than immunohistochemistry. This allows for rapid initiation of treatment in this highly aggressive tumor. However, since its sensitivity is less than 100%, van der Meulen et al., recommend to perform histology plus immunohistochemistry in parallel to flow cytometry 3).