AUTHOR=Cordone Iole , Masi Serena , Giannarelli Diana , Pasquale Alessia , Conti Laura , Telera Stefano , Pace Andrea , Papa Elena , Marino Mirella , de Fabritiis Paolo , Mengarelli Andrea TITLE=Major Differences in Lymphocyte Subpopulations Between Cerebrospinal Fluid and Peripheral Blood in Non-Hodgkin Lymphoma Without Leptomeningeal Involvement: Flow Cytometry Evidence of a Cerebral Lymphatic System JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.685786 DOI=10.3389/fonc.2021.685786 ISSN=2234-943X ABSTRACT=

Cerebrospinal fluid (CSF) flow cytometry has a crucial role in the diagnosis of leptomeningeal disease in onco-hematology. This report describes the flow cytometry characterization of 138 CSF samples from patients affected by non-Hodgkin lymphoma, negative for disease infiltration. The aim was to focus on the CSF non-neoplastic population, to compare the cellular composition of the CSF with paired peripheral blood samples and to document the feasibility of flow cytometry in hypocellular samples. Despite the extremely low cell count (1 cell/µl, range 1.0–35) the study was successfully conducted in 95% of the samples. T lymphocytes were the most abundant subset in CSF (77%; range 20–100%) with a predominance of CD4-positive over CD8-positive T cells (CD4/CD8 ratio = 2) together with a minority of monocytes (15%; range 0–70%). No B cells were identified in 90% of samples. Of relevance, a normal, non-clonal B-cell population was documented in 5/7 (71%) patients with primary central nervous system lymphoma at diagnosis (p<0.0001), suggesting a possible involvement of blood-brain barrier cell permeability in the pathogenesis of cerebral B-cell lymphomas. The highly significant differences between CSF and paired peripheral blood lymphoid phenotype (p<0.0001) confirms the existence of an active mechanism of lymphoid migration through the meninges.