DIAGNOSTIC-VALUE OF CEREBROSPINAL-FLUID CYTOLOGY IN COMPARISON WITH TUMOR-MARKER ACTIVITY IN CENTRAL-NERVOUS-SYSTEM METASTASES SECONDARY TOBREAST-CANCER

Background. Central nervous system (CNS) metastases occur in approxima tely 35% of patients with breast cancer. Parenchymal brain metastases (MET) remain undetected in a large proportion of patients, and only 50 % of patients with leptomeningeal carcinomatosis (MC) are diagnosed in vivo. Methods. Cytology and activity of the tumor markers tissue poly peptide antigen (TPA) and creatine kinase-BB isoenzyme (CK-BB) were ev aluated in the cerebrospinal fluid (CSF) in 71 consecutive patients wi th breast cancer suspected for CNS metastases. Results. Forty-three pa tients had no CNS metastases, 12 patients had MET, 5 patients had both MET and MC, and 11 patients had MC alone. Seven of the patients with MC had an intracerebroventricular (ICV) reservoir inserted, and an add itional 70 ICV CSF samples from these patients were obtained. In CSF o btained by lumbar puncture, 11% of the samples were classified as ''su spicious for malignancy,'' but a very limited interobserver variabilit y was demonstrated (Kappa test value, 0.81; 95% confidence limits, 0.6 7-0.95%). Fifty-one percent of the ICV CSF samples were classified as ''suspicious for malignancy'' (Kappa test value, 0.58; 95% confidence limits, 0.34-0.82%). TPA and CK-BB were both measured in 101 CSF speci mens (61 from lumbar puncture and 40 ICV samples). The differences bet ween patients with and without CNS metastases were significantly diffe rent according to TPA (P < 0.00001) and CK-BB (P < 0.00003; Mann-Whitn ey test). The sensitivity and predictive value of a negative test for having any CNS metastases (in case of elevated values of either TPA or CK-BB or both) were 85% (95% confidence limits, 65-96%) and 90% (95% confidence limits, 76-97%), respectively. In addition, a significant c orrelation between TPA and CK-BB was demonstrated in CSF from lumbar p uncture (Spearmans-Rho, 0.49; P < 0.0001) and ICV (Spearmans-Rho, 0.37 ; P < 0.02). Conclusions. Cytologic evaluation of CSF obtained by lumb ar punctures is a reliable procedure. In CSF from ICV reservoirs, cyto logic evaluation is of limited use, but CK-BB and TPA is of potential value.