BACKGROUND. Detection of malignant cells on cytologic examination of t
he cerebrospinal fluid (CSF) is the diagnostic gold standard for lepto
meningeal carcinomatosis. The absence of cells is a primary endpoint f
or most therapeutic trials. Unfortunately, false-negative results are
common. Practical strategies are necessary to remedy this problem. MET
HODS. Four physician-dependent variables (CSF sample volume, site of C
SF sampling, processing time, and frequency of CSF sampling) were iden
tified, and their contributions to the false-negative rate of CSF cyto
logy were evaluated prospectively in 39 patients with leptomeningeal c
arcinomatosis. Retrospective data were analyzed to estimate the import
ance of these variables in daily practice. RESULTS. False-negative CSF
cytology results correlated with small CSF volume (P < 0.001), delaye
d processing (P < 0.001), not obtaining CSF from a site of symptomatic
or radiographically demonstrated disease (P = 0.02), and sampling few
er 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 s
lowly. CONCLUSIONS. False-negative CSF cytology results are common, bu
t can be minimized by: 1) withdrawing at least 10.5 mL of CSF for cyto
logic analysis; 2) processing the CSF specimen immediately; 3) obtaini
ng CSF from a site of known leptomeningeal disease; and 4) repeating t
his procedure once if the initial cytology is negative. (C) 1998 Ameri
can Cancer Society.