Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results

Cancer. 1998 Feb 15;82(4):733-9. doi: 10.1002/(sici)1097-0142(19980215)82:4<733::aid-cncr17>3.0.co;2-z.

Abstract

Background: Detection of malignant cells on cytologic examination of the cerebrospinal fluid (CSF) is the diagnostic gold standard for leptomeningeal carcinomatosis. The absence of cells is a primary endpoint for most therapeutic trials. Unfortunately, false-negative results are common. Practical strategies are necessary to remedy this problem.

Methods: Four physician-dependent variables (CSF sample volume, site of CSF sampling, processing time, and frequency of CSF sampling) were identified, and their contributions to the false-negative rate of CSF cytology were evaluated prospectively in 39 patients with leptomeningeal carcinomatosis. Retrospective data were analyzed to estimate the importance of these variables in daily practice.

Results: False-negative CSF cytology results correlated with small CSF volume (P < 0.001), delayed processing (P < 0.001), not obtaining CSF from a site of symptomatic or radiographically demonstrated disease (P = 0.02), and sampling fewer than two times (P < 0.001). In 1 year, 97% of CSF specimens at the study institution were of inadequate volume; >25% were processed too slowly.

Conclusions: False-negative CSF cytology results are common, but can be minimized by: 1) withdrawing at least 10.5 mL of CSF for cytologic analysis; 2) processing the CSF specimen immediately; 3) obtaining CSF from a site of known leptomeningeal disease; and 4) repeating this procedure once if the initial cytology is negative.

MeSH terms

  • Cerebrospinal Fluid / cytology*
  • Cytodiagnosis / methods
  • False Negative Reactions
  • Humans
  • Meningeal Neoplasms / pathology*
  • Meningeal Neoplasms / secondary
  • Predictive Value of Tests
  • Retrospective Studies
  • Specimen Handling / methods
  • Spinal Puncture