Blood Neurofilament Light Chains as Biomarkers in CNS Histiocytic Neoplasms
Overview
This study demonstrates that blood neurofilament light chain (NfL) levels are significantly elevated in adults with histiocytic neoplasms involving the central nervous system (CNS), particularly in cases with parenchymal brain involvement and enhancement on MRI. Elevated NfL correlates with active CNS disease, suggesting its potential as a non-invasive biomarker for CNS involvement in these rare neoplasms.
Background
Histiocytic neoplasms are rare hematologic disorders characterized by the accumulation of neoplastic histiocytic or dendritic cells, often accompanied by inflammatory infiltrates. CNS involvement in these diseases is associated with increased morbidity and mortality and is currently assessed primarily through contrast-enhanced brain and spine MRI. Neurofilament light chain (NfL) is a biomarker of axonal injury that can be measured in blood and has shown utility in monitoring neurological disease activity. This study aimed to evaluate whether blood NfL levels are elevated in patients with CNS histiocytic neoplasms and if they correlate with CNS disease activity.
Data Highlights
Group
Number of Patients
Median NfL Level (pg/mL)
Statistical Significance
CNS Histiocytosis with Parenchymal Involvement
27
Significantly elevated
P < 0.0001 vs. non-CNS
CNS Histiocytosis without Parenchymal Involvement
Not specified
Elevated vs. non-CNS but less than parenchymal
P < 0.0001 vs. non-CNS
Histiocytosis without CNS Involvement
56
Lower NfL levels
Reference group
Key Findings
Blood NfL levels were significantly higher in patients with CNS histiocytic neoplasms compared to those without CNS involvement (P < 0.0001).
Among CNS-involved patients, those with parenchymal brain involvement and gadolinium enhancement on MRI had the highest NfL levels.
NfL was measured using two assays (Simoa and Ella), with values harmonized for comparison.
BRAF V600E mutation was present in 43% of tested patients, more frequently in those with CNS involvement (54%) than without (38%).
Clinical and demographic features did not differ significantly between patients with and without CNS involvement.
MRI findings of parenchymal T2 hyperintensity and enhancement correlated with elevated NfL levels, supporting NfL as a marker of active CNS disease.
Clinical Implications
Measurement of blood NfL offers a minimally invasive biomarker to detect and monitor CNS involvement in patients with histiocytic neoplasms. Elevated NfL levels may help identify active CNS disease, particularly parenchymal involvement, potentially guiding clinical decision-making and treatment monitoring alongside MRI. Incorporating NfL testing could improve early detection and management of CNS complications in this patient population.
Conclusion
Blood neurofilament light chain levels are significantly elevated in adults with CNS histiocytic neoplasms, especially with parenchymal brain involvement, reflecting active CNS disease. NfL measurement may serve as a valuable biomarker for CNS involvement and disease activity in these rare neoplasms.
References
Diamond et al. 2023 -- Measurement of Blood Neurofilament Light Chains in Adults Diagnosed with CNS Histiocytic Neoplasms
by Samantha A. Banks, Paul Decker, Eoin P. Flanagan, Anastasia Zekeridou, Ronald S. Go, Jithma P. Abeykoon, Gaurav Goyal, Jason R. Young, Matthew J. Koster, Robert Vassallo, Jay H. Ryu, Caroline J. Davidge-Pitts, Aishwarya Ravindran, Julio C. Sartori Valinotti, N. Nora Bennani, Mithun V. Shah, Karen L. Rech, Corrie R. Bach, Jeanette E. Eckel-Passow, W. Oliver Tobin
