CSF cytology: core principles, diagnostic pitfalls and emerging digital tools including artificial intelligence and telecytology.
26 affiliations
- 1Department of Neurology, Hannover Medical School, 30625, Hannover, Germany. [email protected].
- 2Department of Neurology, Hannover Medical School, 30625, Hannover, Germany.
- 3Department of Neurology, University of Ulm, 89081, Ulm, Germany.
- 4Department of Neurology, Medical University Lausitz-Carl Thiem, 03048, Cottbus, Germany.
- 5Medical Laboratory Bremen, 28355, Bremen, Germany.
- 6Department of Neurology, University Hospital and University Münster, 48149, Münster, Germany.
- 7Department of Neurology, Christian-Doppler University Hospital, Paracelsus Medical University, 5020, Salzburg, Austria.
- 8Department of Dermatology and Allergology, Paracelsus Medical University, 5020, Salzburg, Austria.
- 9Division of Neuroimmunology, Department of Neurology, Heidelberg University Hospital, 69120, Heidelberg, Germany.
- 10Department of Neurology, Friedrich-Alexander-University and University Hospital Erlangen-Nürnberg, 91054, Erlangen, Germany.
- 11Department of Neurodegeneration Diagnostics, Medical University of Białystok, Białystok, Poland.
- 12Department of Biochemical Diagnostics, University Hospital of Białystok, 15-269, Białystok, Poland.
- 13Department of Neurology, Medical University of Graz, 8036, Graz, Austria.
- 14Institute of Clinical Chemistry and Department of Neurology, University Hospital Schleswig-Holstein and Kiel University, 24105, Kiel, Germany.
- 15Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120, Halle (Saale), Germany.
- 16Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Oldenburg, 26129, Oldenburg, Germany.
- 17Infectious Disease Serology and Immunology, Medica Medizinische Laboratorien Dr. F. Kaeppeli AG, 8032, Zurich, Switzerland.
- 18SYNLAB Holding Deutschland GmbH, 86156, Augsburg, Germany.
- 19Department of Neurology, Klinikum Braunschweig, 38126, Brunswick, Germany.
- 20Department of Neurology, Sozialstiftung Bamberg, 96049, Bamberg, Germany.
- 21Department of Neurology, University Medicine Greifswald, Greifswald, Germany.
- 22Department of Psychiatry, Max Planck Institute of Psychiatry, 80804, Munich, Germany.
- 23Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 81377, Munich, Germany.
- 24Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, 37075, Göttingen, Germany.
- 25Labopart Medical Laboratories, 01127, Dresden, Germany.
- 26Department of Neurology, GFO Kliniken Niederrhein, St. Josef Krankenhaus Moers, 47441, Moers, Germany. [email protected].
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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BibTeX
@article{nay2026cytology,
title = {{CSF cytology: core principles, diagnostic pitfalls and emerging digital tools including artificial intelligence and telecytology.}},
author = {Sandra Nay and Franz Felix Konen and Franziska Bachhuber and Alexander Dressel and Deborah Erhart and Andreas Gerritzen and Catharina C Gross and Andrea Harrer and Andrea Hinger and Piotr Lewczuk and Jan Lewerenz and Michael Khalil and Mirjam Korporal-Kuhnke and Frank Leypoldt and Thiemo M Möllenkamp and Markus Otto and Astrid Petersmann and Axel Regeniter and Martin Roskos and Klemens Ruprecht and Annette Spreer and Herwig Strik and Marie Süße and Hayrettin Tumani and Manfred Uhr and Manfred Wick and Brigitte Wildemann and Jens Wiltfang and Thomas Zimmermann and Thomas Skripuletz and Stefan Isenmann and German Society for Cerebrospinal Fluid Diagnostics, Clinical Neurochemistry (DGLN e.V.)},
journal = {Acta neuropathologica},
year = {2026},
month = oct,
doi = {10.1007/s00401-026-03101-7},
url = {https://europepmc.org/article/MED/42961673},
note = {CC BY},
}
RIS
TY - JOUR
TI - CSF cytology: core principles, diagnostic pitfalls and emerging digital tools including artificial intelligence and telecytology.
AU - Sandra Nay
AU - Franz Felix Konen
AU - Franziska Bachhuber
AU - Alexander Dressel
AU - Deborah Erhart
AU - Andreas Gerritzen
AU - Catharina C Gross
AU - Andrea Harrer
AU - Andrea Hinger
AU - Piotr Lewczuk
AU - Jan Lewerenz
AU - Michael Khalil
AU - Mirjam Korporal-Kuhnke
AU - Frank Leypoldt
AU - Thiemo M Möllenkamp
AU - Markus Otto
AU - Astrid Petersmann
AU - Axel Regeniter
AU - Martin Roskos
AU - Klemens Ruprecht
AU - Annette Spreer
AU - Herwig Strik
AU - Marie Süße
AU - Hayrettin Tumani
AU - Manfred Uhr
AU - Manfred Wick
AU - Brigitte Wildemann
AU - Jens Wiltfang
AU - Thomas Zimmermann
AU - Thomas Skripuletz
AU - Stefan Isenmann
AU - German Society for Cerebrospinal Fluid Diagnostics, Clinical Neurochemistry (DGLN e.V.)
PY - 2026
DA - 2026/10/30
JO - Acta neuropathologica
DO - 10.1007/s00401-026-03101-7
UR - https://europepmc.org/article/MED/42961673
AB - 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.
SN - 0001-6322
SN - 1432-0533
ER -