Sensitivity and specificity of cerebrospinal fluid flow cytometry for the diagnosis of leukemic meningitis in acute lymphoblastic leukemia/lymphoma

Abstract

The presence of leukemic blasts detected by light microscopy in cerebrospinal fluid (CSF) establishes the diagnosis of leukemic meningitis in acute lymphoblastic leukemia/lymphoma (ALL). Flow cytometry immunophenotyping (FCI) is a very sensitive method that detects a minute number of aberrant cells, and is increasingly performed on CSF samples. We sought to determine the sensitivity and specificity of CSF FCI for the diagnosis of leukemic meningitis in ALL. Between November 2007 and August 2011, 800 CSF samples from 80 patients with ALL were available from diagnostic lumbar punctures (LPs; n = 80), follow-up LPs (n = 687) and at the time of relapse (n = 33). FCI was performed on 267 samples, and only identified aberrant cells in cytologically confirmed cases of leukemic meningitis. A blinded review of all cases with detectable CSF nucleated cells confirmed these findings. We conclude that CSF FCI has a 100% sensitivity and specificity for the detection of lymphoblasts. However, additional studies are needed to define the role this procedure plays in the diagnosis of leukemic meningitis.

Detection of central nervous system involvement in childhood acute lymphoblastic leukemia by cytomorphology and flow cytometry of the cerebrospinal fluid

“…We report the results of flow cytometric immunophenotyping of the CSF in conjunction with cytomorphology of children newly diagnosed with ALL from two Swedish pediatric oncology units. Our data showed that FCI is more sensitive than conventional CM for detecting CSF involvement, confirming previous observations in leukemia and lymphoma . In this study, CSF involvement was detected by FCI in the two cases with cranial nerve palsy with negative cytology.…”

Accuracy of flow cytometry and cytomorphology for the diagnosis of meningeal involvement in lymphoid neoplasms: A systematic review

“…A total of 41 studies comparing flow cytometry and cytology in CSF samples from patients with lymphoid neoplasia were identified .…”

“…Other authors consider inconclusive morphologies (i.e., neither normal nor clearly pathological) as an indeterminate result. Furthermore, a potentially important source of bias is marginally considered: only 8/27 studies explicitly declare morphological review has been made with pathologists blinded to flow cytometry results, whereas Mitri et al acknowledge in their study slide review has been performed knowing flow cytometry results and even French et al admit cytologists were not blinded to them.…”

“…Despite all the aforementioned methodological differences that could explain the highly variable results reported by single studies, 24/27 studies (89%) report an increase in the number of positive samples obtained using flow cytometry along with conventional cytology. Only three articles did not show this: Baehring et al considered atypical or suspicious flow cytometry results as negative findings; Mitri et al admitted cytopathologists reviewed CSF slides knowing flow cytometry findings, a fact that could have increased concordance rate between the two methods; finally, Liu et al set as a criteria for identification of B‐cell clones a minimum of 100 CD19+ events acquired, a cut‐off that could probably be considered too narrow given hypocellularity is quite frequent in CSF samples. However, almost half of the studies report a low but significant number of samples with positive morphology but negative flow cytometry.…”

Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology

“…No evidence from our SR informed this statement; however, evidence identified outside our SR indicated that flow cytometry can effectively detect disease in CSF samples from patients with ALL 261,262 and can detect subtle leukemic involvement in some cytologically negative CSF samples from both pediatric and adult patients with B-ALL and T-ALL. 263,264 Moreover, patients with ALL and CSF disease not detected by visual inspection of cytocentrifuge preparations but detectable by flow cytometry involvement have shorter OS times than do those with no involvement detected by flow cytometry (P ¼ .01 on multivariate analysis).…”