Novel flowcytometry-based approach of malignant cell detection in body fluids using an automated hematology analyzer

PLoS One. 2018 Feb 9;13(2):e0190886. doi: 10.1371/journal.pone.0190886. eCollection 2018.

Abstract

Morphological microscopic examinations of nucleated cells in body fluid (BF) samples are performed to screen malignancy. However, the morphological differentiation is time-consuming and labor-intensive. This study aimed to develop a new flowcytometry-based gating analysis mode "XN-BF gating algorithm" to detect malignant cells using an automated hematology analyzer, Sysmex XN-1000. XN-BF mode was equipped with WDF white blood cell (WBC) differential channel. We added two algorithms to the WDF channel: Rule 1 detects larger and clumped cell signals compared to the leukocytes, targeting the clustered malignant cells; Rule 2 detects middle sized mononuclear cells containing less granules than neutrophils with similar fluorescence signal to monocytes, targeting hematological malignant cells and solid tumor cells. BF samples that meet, at least, one rule were detected as malignant. To evaluate this novel gating algorithm, 92 various BF samples were collected. Manual microscopic differentiation with the May-Grunwald Giemsa stain and WBC count with hemocytometer were also performed. The performance of these three methods were evaluated by comparing with the cytological diagnosis. The XN-BF gating algorithm achieved sensitivity of 63.0% and specificity of 87.8% with 68.0% for positive predictive value and 85.1% for negative predictive value in detecting malignant-cell positive samples. Manual microscopic WBC differentiation and WBC count demonstrated 70.4% and 66.7% of sensitivities, and 96.9% and 92.3% of specificities, respectively. The XN-BF gating algorithm can be a feasible tool in hematology laboratories for prompt screening of malignant cells in various BF samples.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Ascitic Fluid / pathology
  • Automation, Laboratory / instrumentation
  • Body Fluids / cytology*
  • Cerebrospinal Fluid / cytology
  • Coloring Agents
  • Eosine Yellowish-(YS)
  • Flow Cytometry / instrumentation
  • Flow Cytometry / methods*
  • Flow Cytometry / statistics & numerical data
  • Hematology / instrumentation
  • Humans
  • Leukocyte Count / instrumentation
  • Methylene Blue
  • Microscopy
  • Neoplasms / diagnosis
  • Neoplasms / pathology*
  • Pleural Effusion, Malignant / diagnosis
  • Pleural Effusion, Malignant / pathology

Substances

  • Coloring Agents
  • May-Grunwald Giemsa
  • Methylene Blue
  • Eosine Yellowish-(YS)

Grants and funding

This work was supported in part by a Grant-in-Aid for Scientific Research (C), Japan, and a Grant-in-Aid (S1311011) from the Foundation of Strategic Research Projects in Private Universities from the MEXT, Japan (to YT). We also state that the funder provided support in the form of salaries to authors [KK, AK, and KU], but did not have any judgmental roles in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.