OBJECTIVES: In tumorous impairment of CNS, cytological identification of the neoplastic cells in CSF frequently requires the use of ancillary techniques. Our methods are focused on identifying algorithms that increase the probability of identifying CSF malignant cells. MATERIALS AND METHODS: A total of 1.272 CSF samples from patients with tumorous infiltration of CNS of nonhematologic origin along with 721 samples from patients with hematologic malignancies were analyzed in a complex setting including cytological and immunocytochemical investigations. RESULTS AND DISCUSSION: In CSF diagnostics we are aware of the limited amount of sample combined frequently with neoplastic oligocytosis. Provided atypical, potentially malignant cells in CSF are found, further investigation(s) should maximize the probability of their identification-an appropriate cytological staining and immunocytochemical panel is to be applied. (i) In cases of known recent malignancy: immunoprofile of the recent neoplasm has been considered in immunocytochemical panel. (ii) In patients with a history of malignancy: The propensity to develop a new different malignancy must be taken into account. (iii) Atypical cells found in the CSF of a patient with a negative history of malignancy: Considering the most frequent clinically silent malignancies, stepwise immunocytochemistry is employed. Three milliliter of initial CSF sample represents the absolute minimum to start with. CONCLUSIONS: The steps of the laboratory activity targeted on malignancy in the CSF detection can be expected as follows: (i) The sample will be divided for both nonmorphology and cytopathology investigations. (ii) Basic stainings will triage the samples into those with no suspicion of malignancy and the remaining ones. (iii) Special stainings and stepwise immunocytochemistry will be performed in parallel with the nonmorphology investigations.

Institute of Pathology 1st Faculty of Medicine Charles University and Faculty General Hospital Prague Czech Republic

Laboratory for CSF Neuroimmunology Pathology and Special Diagnostics Topelex Ltd Prague Czech Republic

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Ali, S. Z. , & Cibas, E. S. E. D. S. (2010). The Bethesda System for Reporting Thyroid Cytopathology: Definitions. Criteria and Explanatory Notes: Springer.

Chamberlain, M. C. , Glantz, M. , Groves, M. D. , & Wilson, W. H . (2009). Diagnostic tools for neoplastic meningitis: Detecting disease, identifying patient risk, and determining benefit of treatment. Seminars in Oncology, 36 (4 Suppl 2), S35–S45. PubMed

Chandra, A. , Cross, P. , Denton, K. , Giles, T. , Hemming, D. , Payne, C. , … Wilson, P. (2009). The BSCC Code of Practice – exfoliative cytopathology (excluding gynaecological cytopathology). Cytopathology, 20, 211–223. PubMed

Chivukula, M. , & Dabbs, D. J . (2010). Immunocytology In Dabbs D. J. (Ed.), Diagnostic immunohistochemistry. Theranostic and genomic applications, (pp. 901–922). 3rd edn. Philadelphia: Saunders‐ Elsevier.

Coakham, H. B. , Garson, J. A. , Brownell, B. , Allan, P. M. , Harper, E. I. , Lane, E. B. , & Kemshead, J. T. (1984). Use of monoclonal antibody panel to identify malignant cells in cerebrospinal fluid. Lancet, 1(8386), 1095–1098. PubMed

De May, R. M . (1996). The art and science of Cytopathology. Exfoliative Cytology. Chicago: ASCP Press: 427–462.

Deisenhammer, F. , Bartos, A. , Egg, R. , Gilhus, N. E. , Giovannoni, G. , Rauer, S. , … EFNS Task Force . (2006). Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. European Journal of Neurology, 13, 913–922. PubMed

Fowler, L. J. , & Lachar, W. A. (2008). Application of Immunohistochemistry to Cytology. Archives of Pathology and Laboratory Medicine, 132(3), 373–383. PubMed

Fulciniti, F. , Frangella, C. , Staiano, M. , La Vecchia, F. , Botti, G. , Demuru, A. , … Boon, M. E. (2008). Air‐dried smears for optimal diagnostic immunocytochemistry. Acta Cytologica, 52, 178–186. PubMed

Glantz, M. J. , Cole, B. F. , Glantz, L. K. , et al. (1998). Cerebrospinal fluid cytology in patients with cancer: Minimizing false‐negative results. Cancer, 82, 733–739. PubMed

Kaplan, J. G. , Desouza, T. G. , Farkash, A. , Shafran, B. , Pack, D. , Rehman, F. , … Portenoy, R. (1990). Leptomeningeal metastases: Comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. Journal of Neuro‐Oncology, 9, 225–229. 56. PubMed

Knoepp, S. M. , Placido, J. , Fields, K. L. , Thomas, D. , & Roh, M. H . (2013). The application of immunocytochemistry to direct smears in the diagnosis of effusions. Diagnostic Cytopathology, 41, 425–430. PubMed

Nayar, R. , & Wilbur, D. C . (Eds.). The Bethesda system for reporting cervical cytology. Definitions, criteria, and explanatory notes. Springer; 2015.

Perske, C. H. , Nagel, I. , Nagel, H. , & Strik, H. (2011). CSF Cytology—The Ongoing Dilemma to Distinguish Neoplastic and Inflammatory Lymphocytes. Diagnostic Cytopathology, 39(8), 621–626. PubMed

Pinheiro, C. , Roque, R. , Adriano, A. , Mendes, P. , Praça, M. , Reis, I. , … André, S. (2015). Optimization of immunocytochemistry in cytology: Comparison of two protocols for fixation and preservation on cytospin and smear preparations. Cytopathology, 26, 38–43. PubMed

Rupinder, K. , Shubra, W. , & Kanwal, M. (2013). Rehydration of Air‐Dried Smears versus Wet Fixation: A Cross‐Sectional Study. Acta Cytologica, 57(4), 364–368. PubMed

Sauter, J. L. , Grogg, K. L. , Vrana, J. , Law, M. E. , Halvorson, J. L. , & Henry, M. R. (2016). Young investigator challenge: Validation and optimization of immunohistochemistry protocols for use on cellient cell block specimens. Cancer cytopathology, 124(2), 89–100. https://doi.org/10.1002/cncy.21660 PubMed DOI

Shidham, V. B. , Lindholm, P. F. , Kajdacsy‐Balla, A. , Chang, C. C. , & Komorowski, R. (2000). Methods of cytologic smear preparation and fixation. Effect on the immunoreactivity of commonly used anticytokeratin antibody AE1/AE3. Acta Cytologica., 44, 1015–1022. PubMed

Sobek, O. , Adam, P. , Koudelková, M. , Štourač, P. , & Mareš, J. (2012). The Algorithm of CSF Examination according to the Reccomendation of the Committee of CSF and Neuroimmunology of the Czech Neurological Society. Ceska a Slovenska Neurologie a Neurochirurgie, 75(2), 159–163.

Strik, H. , & Prömmel, P. (2010). Meningeosis neoplastica. Diagnostik und individualisierte Therapie. Nervenarzt, 81, 229–242. PubMed

Swanson, P. E. (2015). Immunohistochemistry as a surrogate for molecular testing: A review. Applied Immunohistochemistry & Molecular Morphology, 23(2), 81–96. PubMed

Twijnstra, A. , Ongerboer, D. V. , & van Zanten, A. P. (1987). Diagnosis of leptomeningeal metastasis. Clinical Neurology and Neurosurgery, 89, 79–85. PubMed

Wasserstrom, W. R. , Glass, J. P. , & Posner, J. B. (1982). Diagnosis and treatment of leptomeningeal metastases from solid tumors: Experience with 90 patients. Cancer, 49, 759–772. PubMed

Weston, C. L. , Glantz, M. J. , & Connor, J. R. (2011). Detection of cancer cells in the cerebrospinal fluid: Current methods and future directions. Fluids and Barriers of the CNS, 8, 14 https://doi.org/10.1186/2045-8118-8-14 PubMed DOI PMC

Zeman, D. , Adam, P. , Kalistova, H. , Sobek, O. , Andel, J. , & Andel, M. (2001). Cerebrospinal fluid cytologic findings in multiple sclerosis. A comparison between patient subgroups. Acta Cytologica, 45, 51–59. PubMed

Recommendations for cerebrospinal fluid analysis