Abstract
Neoplastic cell infiltration into the central nervous system (CNS) is a serious complication of hematological neoplasms. Cytomorphology (CM) and flow cytometry (FC) have been used to detect meningeal infiltration. The association between CSF findings with the results of CM and FC is still poorly understood. We retrospectively evaluated CSF findings in 72 patients with hematological neoplasm and meningeal infiltration detected either by CM or FC. We compared CSF cell count, total protein concentration, and lactate concentration according to the type of hematological neoplasm. We also compared these CSF findings according to the FC and CM results (FC + CM + , FC + CM-, and FC-CM +). The proportion of patients with positive FC was higher than with CM (FC − 91.7%; CM − 63.9%). Thirty-five (48.6%) patients with meningeal infiltration had normal CSF cell count, normal total protein concentration, and normal lactate concentration. The proportion of cases in which these CSF parameters were normal did not differ according to the type of hematological neoplasm. The positivity of CM was significantly higher in patients with > 3 cell/mm3 (P = 0.015) but the positivity of FC was not significantly different between patients with > 3 cell/mm3 or ≤ 3 cells/mm3. Patients with positive CM had more CSF cells (P = 0.0005) and higher lactate concentration (P = 0.0165) than patients with negative CM. The absence of CSF changes in cell count and total protein and lactate concentrations does not exclude the presence of meningeal infiltration. Although CM is considered the gold standard, the probability of positive CM is low in patients without CSF abnormalities in these parameters. Patients with hematological neoplasm with suspected meningeal infiltration should be investigated with both methods.
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References
Chamberlain MC (2006) Neoplastic meningitis. Handb Clin Neurol 105:757–855. https://doi.org/10.1016/B978-0-444-53502-3.00022-7
Liu J, Wang Y, Sun X, Liu S, Yu Z, Ji N, Sun S, Liu Y (2017) Lesions of the central nervous system in leukemia: Pathological and magnetic resonance imaging features at presentation in 14 patients. Oncol Lett 14(6):8162–8170. https://doi.org/10.3892/ol.2017.7192
Del Principe MI, Buccisano F, Soddu S et al (2018) Involvement of central nervous system in adult patients with acute myeloid leukemia: Incidence and impact on outcome. Semin Hematol 55(4):209–214. https://doi.org/10.1053/j.seminhematol.2018.02.006
Bondarenko VP, Tereschenko GV, Andrianov MM et al (2019) Magnetic resonance imaging of changes in the brain of children cured of acute lymphoblastic leukemia. Hematol Rep 11(3):7946. https://doi.org/10.4081/hr.2019.7946
Dušková J, Sobek O (2017) Assisting the neurologist in diagnosis of CNS malignancies—current possibilities and limits of cerebrospinal fluid cytology and immunocytochemistry. Brain Behav 7(10):e00805. https://doi.org/10.1002/brb3.805
Galati D, Di Noto R, Del Vecchio L (2013) Diagnostic strategies to investigate cerebrospinal fluid involvement in haematological malignancies. Leuk Res 37(3):231–237. https://doi.org/10.1016/j.leukres.2012.11.016
Subirá D, Castañón S, Román A et al (2001) Flow cytometry and the study of central nervous disease in patients with acute leukaemia. Br J Haematol 112(2):381–384. https://doi.org/10.1046/j.1365-2141.2001.02505.x
Nückel H, Novotny JR, Noppeney R, Savidou I, Dührsen U (2006) Detection of malignant haematopoietic cells in the cerebrospinal fluid by conventional cytology and flow cytometry. Clin Lab Haematol 28(1):22–29. https://doi.org/10.1111/j.1365-2257.2006.00741.x
Hegde U, Filie A, Little RF et al (2005) High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology. Blood 105(2):496–502. https://doi.org/10.1182/blood-2004-05-1982
Di Noto R, Scalia G, Abate G et al (2008) Critical role of multidimensional flow cytometry in detecting occult leptomeningeal disease in newly diagnosed aggressive B-cell lymphomas. Leuk Res 32(8):1196–1199. https://doi.org/10.1016/j.leukres.2007.12.016
Bento LC, Correia RP, Alexandre AM et al (2018) Detection of central nervous system infiltration by myeloid and lymphoid hematologic neoplasms using flow cytometry analysis: diagnostic accuracy study. Front Med (Lausanne) 5:70. https://doi.org/10.3389/fmed.2018.00070
Rahimi J, Woehrer A (2017) Overview of cerebrospinal fluid cytology. Handb Clin Neurol 145:563–571. https://doi.org/10.1016/B978-0-12-802395-2.00035-3
Giovannoni G (2014) Cerebrospinal fluid analysis. Handb Clin Neurol 122:681–702. https://doi.org/10.1016/B978-0-444-52001-2.00029-7
Kraan J, Gratama JW, Haioun C et al (2008) Flow cytometric immunophenotyping of cerebrospinal fluid. Curr Protoc Cytom 6:25. https://doi.org/10.1002/0471142956.cy0625s45
Bromberg JE, Breems DA, Kraan J et al (2007) CSF flow cytometry greatly improves diagnostic accuracy in CNS hematologic malignancies. Neurology 68(20):1674–1679. https://doi.org/10.1212/01.wnl.0000261909.28915.83
Craig FE, Ohori NP, Gorrill TS, Swerdlow SH (2011) Flow cytometric immunophenotyping of cerebrospinal fluid specimens. Am J Clin Pathol 135(1):22–34. https://doi.org/10.1309/AJCPANA7ER1ABMZI
Pui CH, Thiel E (2009) Central nervous system disease in hematologic malignancies: historical perspective and practical applications. Semin Oncol 36(4 Suppl 2):S2–S16. https://doi.org/10.1053/j.seminoncol.2009.05.002
Subirá D, Castañón S, Aceituno E et al (2002) Flow cytometric analysis of cerebrospinal fluid samples and its usefulness in routine clinical practice. Am J Clin Pathol 117(6):952–958. https://doi.org/10.1309/123P-CE6V-WYAK-BB1F
Finn WG, Peterson LC, James C, Goolsby CL (1998) Enhanced detection of malignant lymphoma in cerebrospinal fluid by multiparameter flow cytometry. Am J Clin Pathol 110(3):341–346. https://doi.org/10.1093/ajcp/110.3.341
Djukic M, Trimmel R, Nagel I, Spreer A, Lange P, Stadelmann C, Nau R (2017) Cerebrospinal fluid abnormalities in meningeosis neoplastica: a retrospective 12-year analysis. Fluids Barriers CNS 14(1):7. https://doi.org/10.1186/s12987-017-0057-2
Kelbich P, Hejčl A, Krulichová IS et al (2014) Coefficient of energy balance, a new parameter for basic investigation of the cerebrospinal fluid. Clin Chem Lab Med 52(7):1009–1017. https://doi.org/10.1515/cclm-2013-0953
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by RBD, FBVML and CS. The first draft of the manuscript was written by RBD and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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The human tissue and fluid samples analyzed were obtained from patients routinely subjected to CSF analysis irrespective of this study. The study did not offer any direct benefits to patients or interfere with patient diagnosis or treatment.
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Domingues, R.B., de Moura Leite, F.B.V. & Senne, C. Cerebrospinal fluid findings in patients with hematologic neoplasms and meningeal infiltration. Acta Neurol Belg 121, 1543–1546 (2021). https://doi.org/10.1007/s13760-020-01397-0
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DOI: https://doi.org/10.1007/s13760-020-01397-0