Soon after the introduction of lumbar puncture by Quincke and Wynter2 in 1891, early “cytologists”(predominantly neurologists and hematologists) recognized the clinical relevance of identifying and quantifying the cells in cerebrospinal fluid (CSF). These investigators relied on CSF leukocytosis and lymphocytosis to distinguish acute bacterial meningitis from tuberculous and/or syphilitic meningitis. The development of lenses, cell-counting chambers, and staining methodologies facilitated microscopic examination of CSF; early in the twentieth century, descriptions of primary central nervous system (CNS) tumors, metastatic carcinoma, and leukemic infiltrate6 in CSF smears were published. Cytologic evaluation of CSF can be difficult. Contributing; factors include (1) small volume of specimen collected and usually shared among several laboratories;(2) low cellularity;(3) rapid degeneration of exfoliated cells;(4) difficulty in obtaining additional specimen;(5) major indication for CSF examination being to diagnose symptomatic patients rather than to screen asymptomatic patients;(6) uncertain origin of some benign cells (7) overlapping cytomorphologic features of some benign and malignant cells;(8) the tendency of most primary CNS tumors not to exfoliate into CSF;(9) malignant diagnoses often based on very few cells;(10) malignant diagnoses often not confirmed histologically;(1 1) malignant diagnoses mandate therapies associated with significant morbidity;(12) malignant diagnoses associated with bleak clinical prognoses; and (1 3) lack of premalignant lesions recognized.

Since 1991 marks the centennial of the lumbar puncture, it may be particularly appropriate to ask,“What’s new in CSF cytology? What’s new in CNS cytology?” This review does not summarize or reiterate the large body of extant literature devoted to CNS cytology but addresses