CSF cytology: core principles, diagnostic pitfalls and emerging digital tools including artificial intelligence and telecytology

Abstract Cerebrospinal fluid cytology remains a cornerstone of diagnostic evaluation in infectious, autoimmune, haemorrhagic, and neoplastic disorders of the central nervous system despite advances in neuroimaging, molecular diagnostics, and digital technologies. This narrative review summarises established principles of cerebrospinal fluid cytology, highlights methodological limitations and diagnostic pitfalls, and integrates emerging developments, including automated cell counting, artificial intelligence, and telecytology. Pre-analytical factors are critical determinants of diagnostic accuracy. Delayed sample processing promotes pH-dependent autolysis and substantial cell loss, whereas rapid cytocentrifugation preserves cellular morphology and facilitates reliable assessment. Automated cell counters are increasingly implemented in routine laboratories and offer advantages in settings with limited technical staffing. However, current systems show limited precision in samples with low and slightly elevated cell counts and limited morphological evaluation. Manual chamber counting, particularly in the normal and low-cell-count range, remains the gold standard for quantitative CSF cell assessment, whereas expert microscopic examination remains the reference standard for qualitative cytomorphological assessment. Although the sensitivity of neuroimaging continues to improve, cerebrospinal fluid cytology retains a unique diagnostic role in the detection of infectious and neoplastic conditions and in the evaluation of subarachnoid haemorrhage. Cytological detection of erythrophages, siderophages, and haematoidin crystals can reveal haemorrhage and provide clues to its temporal stage. Overall, cerebrospinal fluid cytology remains a valuable diagnostic tool when integrated with clinical, laboratory, microbiological, immunological, and imaging findings. Careful recognition of common pitfalls is essential. We recommend rapid cerebrospinal fluid processing, routine preparation of cytospin-based stained slides with expert microscopic review, and the implementation of automated or digital methods only within clearly validated workflows.

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Publication Details

Journal
Acta Neuropathologica
Published
2026-10-30
DOI
https://doi.org/10.1007/s00401-026-03101-7
Primary Topic
Clinical Laboratory Practices and Quality Control
Type
article
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article

CSF cytology: core principles, diagnostic pitfalls and emerging digital tools including artificial intelligence and telecytology

Thomas Skripuletz, Jan Lewerenz, Manfred Uhr, Jens Wiltfang et al.
Acta Neuropathologica
Clinical Laboratory Practices and Quality Control
article

CSF cytology: core principles, diagnostic pitfalls and emerging digital tools including artificial intelligence and telecytology

Thomas Skripuletz, Jan Lewerenz, Manfred Uhr, Jens Wiltfang, Astrid Petersmann, Sandra Nay, Frank Leypoldt, Hayrettin Tumani, Brigitte Wildemann, Herwig Matthias Strik, Klemens Ruprecht, Annette Spreer, Piotr Lewczuk, Deborah K. Erhart, Andrea Harrer, Andreas Gerritzen, Catharina C. Groß, Mirjam Korporal‐Kuhnke, Michael Khalil, Franz Felix Konen, Markus Otto, Axel Regeniter, Martin Roskos, Marie Süße, Stefan Isenmann, Franziska Bachhuber, Alexander Dressel, Thomas Philipp Zimmermann, Thiemo Malte Möllenkamp, Manfred Wolfgang Wick, Andrea Hinger
article en

Abstract

Abstract Cerebrospinal fluid cytology remains a cornerstone of diagnostic evaluation in infectious, autoimmune, haemorrhagic, and neoplastic disorders of the central nervous system despite advances in neuroimaging, molecular diagnostics, and digital technologies. This narrative review summarises established principles of cerebrospinal fluid cytology, highlights methodological limitations and diagnostic pitfalls, and integrates emerging developments, including automated cell counting, artificial intelligence, and telecytology. Pre-analytical factors are critical determinants of diagnostic accuracy. Delayed sample processing promotes pH-dependent autolysis and substantial cell loss, whereas rapid cytocentrifugation preserves cellular morphology and facilitates reliable assessment. Automated cell counters are increasingly implemented in routine laboratories and offer advantages in settings with limited technical staffing. However, current systems show limited precision in samples with low and slightly elevated cell counts and limited morphological evaluation. Manual chamber counting, particularly in the normal and low-cell-count range, remains the gold standard for quantitative CSF cell assessment, whereas expert microscopic examination remains the reference standard for qualitative cytomorphological assessment. Although the sensitivity of neuroimaging continues to improve, cerebrospinal fluid cytology retains a unique diagnostic role in the detection of infectious and neoplastic conditions and in the evaluation of subarachnoid haemorrhage. Cytological detection of erythrophages, siderophages, and haematoidin crystals can reveal haemorrhage and provide clues to its temporal stage. Overall, cerebrospinal fluid cytology remains a valuable diagnostic tool when integrated with clinical, laboratory, microbiological, immunological, and imaging findings. Careful recognition of common pitfalls is essential. We recommend rapid cerebrospinal fluid processing, routine preparation of cytospin-based stained slides with expert microscopic review, and the implementation of automated or digital methods only within clearly validated workflows.

Acta NeuropathologicaVol. 152(1)
Carl von Ossietzky Universität Oldenburg (DE), Medical University of Białystok (PL), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), Universität Ulm (DE), Medical University of Graz (AT), Heidelberg University (DE), University of Münster (DE), Paracelsus Medical University (AT), Universitätsmedizin Greifswald (DE), University Hospital Heidelberg (DE), LMU Klinikum (DE), Medizinische Hochschule Hannover (DE), Universitätsklinikum Erlangen (DE), University Hospital Münster (DE), Christian Doppler Klinik (AT), University Hospital Schleswig-Holstein (DE), Klinikum Braunschweig (DE), Universitätsmedizin Göttingen (DE), Synlab (Germany) (DE), Medizinische Universität Lausitz - Carl Thiem (DE), Max Planck Institute of Psychiatry (DE), Sozialstiftung Bamberg (DE), Institut für Laboratoriumsmedizin (DE), Martin Luther University Halle-Wittenberg (DE), Ludwig-Maximilians-Universität München (DE), University of Lübeck (DE)
Openalex Percentile: Top 12%
Clinical Laboratory Practices and Quality Control
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