Detection of Central Nervous System Infiltration by Myeloid and Lymphoid Hematologic Neoplasms Using Flow Cytometry Analysis: Diagnostic Accuracy Study

Abstract

IntroductionInfiltration of the central nervous system (CNS) by hematologic or lymphoid malignant cells can cause extensive neurological damage, be progressive and fatal. However, usually, the cerebrospinal fluid (CSF) has low cellularity and rapid cell degeneration, which can impair cytometry analysis. Storage and transport measures, sample preparation, and staining protocols can interfere with diagnostic accuracy.ObjectiveTo calculate the diagnostic performance of flow cytometry (FC) using a cell stabilizer for sample preservation compared to cytomorphology in the detection of CNS infiltration by lymphoid and hematologic neoplasms.MethodsCell samples from all consecutive patients with suspected infiltration by hematological malignancies evaluated between January 2014 and December 2016 were included. Cases were analyzed by FC using a cell preservation medium and cytomorphology. Sensitivity and specificity were calculated.ResultsFrom 414 CSF samples, 72 had a phenotype compatible with characteristics of infiltration by hematological disease, whereas cytology was positive for 35 cases. FC showed higher sensitivity and specificity when compared to cytomorphology, particularly in cases with cellularity under 5 leukocytes/mm3.ConclusionWe demonstrated that collecting CSF in a medium that preserves the stability of the sample improves accuracy when compared to cytomorphology, particularly in low-volume and low-cellularity samples.

ESCCA/ISCCA protocol for the analysis of cerebrospinal fluid by multiparametric flow‐cytometry in hematological malignancies

“…In a series of 246 patients affected with DLBCL and 80 affected with BL, Wilson et al (2014) confirmed the superiority of MFC over CC. Therefore, MFC appears an excellent candidate, better than CC, to handle specimens such as CSF characterized by a “scarce event” situation (Bento et al, 2018; Craig et al, 2011; Nückel et al, 2006). This peculiarity was confirmed in pediatric ALL patients in whom MFC was able to ameliorate significantly the demonstration of occult CSF involvement (Popov et al, 2019; Swinburne et al, 2019).…”

Technological features of blast identification in the cerebrospinal fluid: A systematic review of flow cytometry and laboratory haematology methods

“…Neuroimaging by MRI or other techniques, although quite sensitive, have limited specificity. Cytomorphologic examination of the CSF is considered the “gold standard” for CNS involvement by haematologic malignancy due to its high specificity, although with limited sensitivity 5,7 …”

Cerebrospinal fluid cytology in a young adult with seizures

“…Infiltration of the CNS by lymphoid malignancies can cause extensive neurological damage, be progressive and fatal. Meningeal infiltration by neoplastic cells occurs in approximately 5%‐15% of patients with leukaemia and lymphoma 3 . Involvement of the central nervous system by ALCL has been reported in less than 3% of all cases 4 .…”

“…However, owing to the low cellularity and rapid cell degeneration, establishing such a cytomorphologic diagnosis is often challenging. Additionally, storage and transport measures, sample preparation, and staining protocols can interfere with the diagnostic accuracy 3 …”