title: Diagnostic value of cerebrospinal fluid cytology in comparison with tumor marker activity in central nervous system metastases secondary to breast cancer.
abstract: BACKGROUND
  Central nervous system (CNS) metastases occur in approximately 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 polypeptide antigen (TPA) and creatine kinase-BB isoenzyme (CK-BB) were evaluated in the cerebrospinal fluid (CSF) in 71 consecutive patients with breast cancer suspected for CNS metastases.
  
  
  RESULTS
  Forty-three patients 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 additional 70 ICV CSF samples from these patients were obtained. In CSF obtained by lumbar puncture, 11% of the samples were classified as "suspicious for malignancy," but a very limited interobserver variability was demonstrated (Kappa test value, 0.81; 95% confidence limits, 0.67-0.95%). 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 specimens (61 from lumbar puncture and 40 ICV samples). The differences between patients with and without CNS metastases were significantly different according to TPA (P < 0.00001) and CK-BB (P < 0.00003; Mann-Whitney 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 correlation between TPA and CK-BB was demonstrated in CSF from lumbar puncture (Spearmans-Rho, 0.49; P < 0.0001) and ICV (Spearmans-Rho, 0.37; P < 0.02).
  
  
  CONCLUSIONS
  Cytologic evaluation of CSF obtained by lumbar punctures is a reliable procedure. In CSF from ICV reservoirs, cytologic evaluation is of limited use, but CK-BB and TPA is of potential value.
authors.affiliation: Department of Oncology, Herlev Hospital, University of Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Bach
authors.forename: B
authors.initials: B
authors.lastname: Bjerregaard
authors.forename: G
authors.initials: G
authors.lastname: Sölétormos
authors.forename: F W
authors.initials: FW
authors.lastname: Bach
authors.forename: T
authors.initials: T
authors.lastname: Horn
mesh_terms: D000951:Antigens, Neoplasm / Q000134:cerebrospinal fluid; D014408:Biomarkers, Tumor / Q000134:cerebrospinal fluid; D001943:Breast Neoplasms / Q000134:cerebrospinal fluid / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000134:cerebrospinal fluid* / Q000556:secondary*; D002552:Cerebral Ventricles; D002555:Cerebrospinal Fluid / Q000166:cytology; D003402:Creatine Kinase / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007527:Isoenzymes; D010455:Peptides / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D013129:Spinal Puncture; D019396:Tissue Polypeptide Antigen
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007527:Isoenzymes; D010455:Peptides; D019396:Tissue Polypeptide Antigen; D003402:Creatine Kinase