Cerebrospinal Fluid Pleocytosis Pitfalls and Benefits of Combined Analysis Using Cytomorphology and Flow Cytometry

BACKGROUND: Cerebrospinal fluid samples with doubtful morphologic interpretation are a common problem in the workup of patients with clinical signs for leptomeningeal disease. The authors report on the combination of morphology and flow cytometry in the diagnosis of leptomeningeal disease in patients with radiological, clinical, or cytological findings suspicious for leukemia or lymphoma with spread into the cerebrospinal fluid. METHODS: The authors defined a set of antibodies for flow cytometric analysis, which is capable of distinguishing between malignant and nonmalignant hematopoietic cells. One hundred twenty-seven cases were analyzed with both methods. RESULTS: The additional application of flow cytometry resulted in an improvement of diagnostic reliability in 29 of 127 cases. Diagnostic sensitivity was raised from 73% (cytology) to 96% (flow cytometry), specificity from 94% to 97%, the positive predictive value from 88% to 96%, and the negative predictive value from 76% to 97%. CONCLUSIONS: Because the appropriate selection of markers is crucial to successful analysis, the authors suggested a highly selected panel of antibodies for flow cytometry analysis of cerebrospinal fluid samples. The authors were able to demonstrate that leptomeningeal disease caused by leukemia or lymphoma can be diagnosed by flow cytometry and discriminated from reactive pleocytosis in most cases of doubtful morphology. Cancer (Cancer Cytopathol) 2011;119:20-6. (C) 2011 American Cancer Society.