Standardizing a volume benchmark for cerebrospinal fluids for optimal diagnostic accuracy

Abstract

IntroductionCerebral spinal fluid (CSF) cytomorphologic analysis remains the gold standard in the evaluation of malignant leptomeningeal involvement. However, collection of optimal volumes for adequate cytomorphologic evaluation is not standardized. Our study investigated optimal CSF volumes that result in a significant diagnostic result.MethodsA total of 4114 samples were retrospectively identified from 2014 to 2018, and 2557 samples had concurrent flow cytometry (FC) study. Each specimen was grouped as unsatisfactory, negative, atypical, or positive. Positive samples were grouped as either solid tumors, leukemia, or lymphoma by the type of malignancy detected. Demographic data as well as CSF source was recorded. Specimens with FC were separated by detection on cytology and/or FC. A t‐test and ANOVA test were used to compare the average volumes for each group.ResultsAverage volumes for negative, atypical, and positive samples are 7.48 mL (95% CI: 7.33, 7.63), 7.97 mL (95% CI: 7.37, 8.57), and 8.44 mL (95% CI: 7.46, 9.43), respectively. Average volumes for solid tumors, leukemia, and lymphoma positive samples are 12.0 mL (95% CI: 9.11, 14.89), 6.73 mL (95% CI: 5.94, 7.53), and 8.44 mL (95% CI: 6.78, 10.09). For cases with FC, the volumes are 10.11 mL (95% CI: 9.28, 10.96), 7.28 mL (95% CI: 6.87, 7.70), and 6.86 mL (95% CI: 6.25, 7.49) for positive cytology only, positive cytology/FC, and negative for both, respectively.ConclusionsOur results suggest that higher volumes produce better results for analysis. We recommend an optimal volume of 8.44 mL for cytologic work‐up of malignancies. However, optimal volumes may differ based upon malignancy type and utilization of flow cytometry.

Diagnostic accuracy of cerebrospinal fluid liquid biopsy and MRI for leptomeningeal metastases in solid cancers: A systematic review and meta-analysis

“… 28–30 The optimal evaluation of CSF cytology depends on an adequate CSF volume and cell counts, rapid processing, and a skilled examiner. 6 , 33 , 34 In addition to practical issues, the sensitivity of CSF cytology had been assessed in a small-size of subjects with heterogeneous conditions thus contained outliers among the previous reports.…”

Flow Cytometric Detection of Malignant Blasts in Cerebrospinal Fluid: A Biomarker of Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia

“…Often only a few milliliters of CSF are used for preparing cytospin [ 19 ], and with small sample volumes, the scarce leukemic blasts might be missed. Using higher volumes of CSF increases the sensitivity of the analysis, and previous studies have recommended the collection of between 8.5 and 10.5 mL of CSF to obtain >90% sensitivity [ 19 , 20 ]. However, sampling of such large volumes will not be feasible for all children.…”