Skip to main content
Top
Published in: Fluids and Barriers of the CNS 1/2017

Open Access 01-12-2017 | Research

Cerebrospinal fluid abnormalities in meningeosis neoplastica: a retrospective 12-year analysis

Authors: Marija Djukic, Ralf Trimmel, Ingelore Nagel, Annette Spreer, Peter Lange, Christine Stadelmann, Roland Nau

Published in: Fluids and Barriers of the CNS | Issue 1/2017

Login to get access

Abstract

Background

Meningeosis neoplastica is a diffuse metastatic spread of tumor cells in the subarachnoid space. Although first recognized in 1870, systematic investigations regarding cerebrospinal fluid (CSF) constituents in this condition are scarce.

Methods

Routine CSF samples analyzed from 2001 to 2012 at the Laboratory of Clinical Neurochemistry, University of Göttingen, were re-evaluated. Patients, whose CSF contained malignant cells were included in this study.

Results

Patients (n = 132, age 59.1 ± 29.1, 58% women) were identified, whose CSF contained malignant cells. The most frequent primary tumor was breast cancer (32.6%), followed by lung cancer (25.0%) and hematologic malignancies (21.2%). The most frequent clinical symptoms were affections of cranial nerves (41.7%), psychiatric abmormalities (32.6%) and radicular lesions of the lower extremities (20.5%). CSF cell counts ranged from 0 to 4692 cells/μl (median 4 cells/μl) and were elevated in 50%. The CSF-to-serum albumin ratio was abnormal in 69.4%. It ranged from 1.8 to 330 x 10-3 (median 17.5 x 10-3). Total CSF protein ranged from 166 to 15,840 mg/l (median 1012 mg/l). CSF lactate was elevated (>2.4 mmol/l) in 65.2% [3.6 mmol/l (1.3/15.6 mmol/l); median (minimum/maximum)]. In 50% of all patients CSF lactate was ≥3.5 mmol/l. The CSF cell counts correlated significantly with the CSF lactate levels and the CSF protein contents. In 56 of 118 CSF samples (47.5%) ferritin was elevated, and in 25 of 65 carcinoma patients (38.5%) an intrathecal production of carcinoembryonic antigen (CEA) was detected. Granulocytes were found in 52.7% of the CSF samples. The percentages of granulocytes and lymphocytes were higher in samples with an elevated cell count.

Conclusion

In approximately 50% of CSF samples with meningeosis neoplastica the CSF cell count is not elevated. Diagnosis may be missed when only CSF samples with elevated cell counts are subjected to cytological analysis. CSF lactate and protein and the CSF-to-serum albumin ratio are frequently increased in meningeosis neoplastica. The differential diagnosis between meningeosis neoplastica and central nervous infections, in particular tuberculous or fungal meningitis, can be difficult.
Literature
1.
go back to reference Eberth CJ. Zur Entwicklung des Epitheliomas (Cholesteatomas) der Pia und der Lunge. Virchow’s Arch. 1870;49:51–63.CrossRef Eberth CJ. Zur Entwicklung des Epitheliomas (Cholesteatomas) der Pia und der Lunge. Virchow’s Arch. 1870;49:51–63.CrossRef
2.
3.
go back to reference Kaplan JG, DeSouza TG, Farkash A, Shafran B, Pack D, Rehman F, Fuks J, Portenoy R. Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol. 1990;9:225–9.CrossRefPubMed Kaplan JG, DeSouza TG, Farkash A, Shafran B, Pack D, Rehman F, Fuks J, Portenoy R. Leptomeningeal metastases: comparison of clinical features and laboratory data of solid tumors, lymphomas and leukemias. J Neurooncol. 1990;9:225–9.CrossRefPubMed
4.
go back to reference Rosen ST, Aisner J, Makuch RW, Matthews MJ, Ihde DC, Whitacre M, Glatstein EJ, Wiernik PH, Lichter AS, Bunn PA Jr. Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the national cancer institute experience. Medicine (Baltimore). 1982;61:45–53.CrossRef Rosen ST, Aisner J, Makuch RW, Matthews MJ, Ihde DC, Whitacre M, Glatstein EJ, Wiernik PH, Lichter AS, Bunn PA Jr. Carcinomatous leptomeningitis in small cell lung cancer: a clinicopathologic review of the national cancer institute experience. Medicine (Baltimore). 1982;61:45–53.CrossRef
6.
go back to reference Le Rhun E, Taillibert S, Chamberlain MC. Carcinomatous meningitis: leptomeningeal metastases in solid tumors. Surg Neurol Int. 2013;4(Suppl 4):265–88. Le Rhun E, Taillibert S, Chamberlain MC. Carcinomatous meningitis: leptomeningeal metastases in solid tumors. Surg Neurol Int. 2013;4(Suppl 4):265–88.
7.
go back to reference Morikawa N, Mori T, Kawashima H, Fujiki M, Abe T, Kaku T, Konisi Y, Takeyama M, Hori S. Pharmacokinetics of nimustine, methotrexate, and cytosine arabinoside during cerebrospinal fluid perfusion chemotherapy in patients with disseminated brain tumors. Eur J Clin Pharmacol. 1998;54:415–20.CrossRefPubMed Morikawa N, Mori T, Kawashima H, Fujiki M, Abe T, Kaku T, Konisi Y, Takeyama M, Hori S. Pharmacokinetics of nimustine, methotrexate, and cytosine arabinoside during cerebrospinal fluid perfusion chemotherapy in patients with disseminated brain tumors. Eur J Clin Pharmacol. 1998;54:415–20.CrossRefPubMed
8.
go back to reference Reiber H. Eine schnelle und einfache nephelometrische Bestimmungsmethode für Protein im Liquor cerebrospinalis. J Clin Chem Clin Biochem. 1980;18:123–7.PubMed Reiber H. Eine schnelle und einfache nephelometrische Bestimmungsmethode für Protein im Liquor cerebrospinalis. J Clin Chem Clin Biochem. 1980;18:123–7.PubMed
9.
go back to reference Reiber H, Felgenhauer K. Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta. 1987;163:319–28.CrossRefPubMed Reiber H, Felgenhauer K. Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta. 1987;163:319–28.CrossRefPubMed
11.
go back to reference Wildemann B, Oschmann P, Reiber H. Neurologische Labordiagnostik. Stuttgart: Georg Thieme Verlag; 2006.CrossRef Wildemann B, Oschmann P, Reiber H. Neurologische Labordiagnostik. Stuttgart: Georg Thieme Verlag; 2006.CrossRef
12.
go back to reference Weston CL, Glantz MJ, Connor JR. Detection of cancer cells in the cerebrospinal fluid: current methods and future directions. Fluids Barriers CNS. 2011;8(1):14.CrossRefPubMedPubMedCentral Weston CL, Glantz MJ, Connor JR. Detection of cancer cells in the cerebrospinal fluid: current methods and future directions. Fluids Barriers CNS. 2011;8(1):14.CrossRefPubMedPubMedCentral
13.
go back to reference Jacobi C, Reiber H, Felgenhauer K. The clinical relevance of locally produced carcinoembryonic antigen in cerebrospinal fluid. J Neurol. 1986;233:358–61.CrossRefPubMed Jacobi C, Reiber H, Felgenhauer K. The clinical relevance of locally produced carcinoembryonic antigen in cerebrospinal fluid. J Neurol. 1986;233:358–61.CrossRefPubMed
14.
go back to reference Petereit HF, Sindern E, Wick M. Leitlinien der Liquordiagnostik und Methodenkatalog der Deutschen Gesellschaft für Liquordiagnostik und Klinische Neurochemie. Heidelberg: Springer; 2007.CrossRef Petereit HF, Sindern E, Wick M. Leitlinien der Liquordiagnostik und Methodenkatalog der Deutschen Gesellschaft für Liquordiagnostik und Klinische Neurochemie. Heidelberg: Springer; 2007.CrossRef
15.
go back to reference Liu J, Jia H, Yang Y, Dai W, Su X, Zhao G. Cerebrospinal fluid cytology and clinical analysis of 34 cases with leptomeningeal carcinomatosis. J Int Med Res. 2009;37:1913–20.CrossRefPubMed Liu J, Jia H, Yang Y, Dai W, Su X, Zhao G. Cerebrospinal fluid cytology and clinical analysis of 34 cases with leptomeningeal carcinomatosis. J Int Med Res. 2009;37:1913–20.CrossRefPubMed
16.
go back to reference Hornig CR, Busse O, Kaps M. Importance of cerebrospinal fluid lactate determination in neurological diseases. Klin Wochenschr. 1983;61:357–61.CrossRefPubMed Hornig CR, Busse O, Kaps M. Importance of cerebrospinal fluid lactate determination in neurological diseases. Klin Wochenschr. 1983;61:357–61.CrossRefPubMed
17.
go back to reference Wellmer A, Prange J, Gerber J, Zysk G, Lange P, Michel U, Eiffert H, Nau R. d- and l-lactate in rabbit and human bacterial meningitis. Scand J Infect Dis. 2001;33:909–13.CrossRefPubMed Wellmer A, Prange J, Gerber J, Zysk G, Lange P, Michel U, Eiffert H, Nau R. d- and l-lactate in rabbit and human bacterial meningitis. Scand J Infect Dis. 2001;33:909–13.CrossRefPubMed
18.
go back to reference Giulieri S, Chapuis-Taillard C, Jaton K, Cometta A, Chuard C, Hugli O, Du Pasquier R, Bille J, Meylan P, Manuel O, Marchetti O. CSF lactate for accurate diagnosis of community-acquired bacterial meningitis. Eur J Clin Microbiol Infect Dis. 2015;34:2049–55.CrossRefPubMed Giulieri S, Chapuis-Taillard C, Jaton K, Cometta A, Chuard C, Hugli O, Du Pasquier R, Bille J, Meylan P, Manuel O, Marchetti O. CSF lactate for accurate diagnosis of community-acquired bacterial meningitis. Eur J Clin Microbiol Infect Dis. 2015;34:2049–55.CrossRefPubMed
19.
go back to reference de Almeida SM, Boritza K, Cogo LL, Pessa L, França J, Rota I, Muro M, Ribeiro C, Raboni SM, Vidal LR, Nogueira MB, Ellis R. Quantification of cerebrospinal fluid lactic acid in the differential diagnosis between HIV chronic meningitis and opportunistic meningitis. Clin Chem Lab Med. 2011;49:891–6.CrossRefPubMed de Almeida SM, Boritza K, Cogo LL, Pessa L, França J, Rota I, Muro M, Ribeiro C, Raboni SM, Vidal LR, Nogueira MB, Ellis R. Quantification of cerebrospinal fluid lactic acid in the differential diagnosis between HIV chronic meningitis and opportunistic meningitis. Clin Chem Lab Med. 2011;49:891–6.CrossRefPubMed
20.
go back to reference Djukic M, Schmidt-Samoa C, Lange P, Spreer A, Neubieser K, Eiffert H, Nau R, Schmidt H. Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis. J Neurol. 2012;259:630–6.CrossRefPubMed Djukic M, Schmidt-Samoa C, Lange P, Spreer A, Neubieser K, Eiffert H, Nau R, Schmidt H. Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis. J Neurol. 2012;259:630–6.CrossRefPubMed
21.
go back to reference Thwaites GE, Chau TT, Stepniewska K, Phu NH, Chuong LV, Sinh DX, White NJ, Parry CM, Farrar JJ. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. Lancet. 2002;360:1287–92.CrossRefPubMed Thwaites GE, Chau TT, Stepniewska K, Phu NH, Chuong LV, Sinh DX, White NJ, Parry CM, Farrar JJ. Diagnosis of adult tuberculous meningitis by use of clinical and laboratory features. Lancet. 2002;360:1287–92.CrossRefPubMed
22.
go back to reference Zou Y, He J, Guo L, Bu H, Liu Y. Prediction of cerebrospinal fluid parameters for tuberculous meningitis. Diagn Cytopathol. 2015;43:701–4.CrossRefPubMed Zou Y, He J, Guo L, Bu H, Liu Y. Prediction of cerebrospinal fluid parameters for tuberculous meningitis. Diagn Cytopathol. 2015;43:701–4.CrossRefPubMed
23.
go back to reference Schumacher M, Orszagh M. Imaging techniques in neoplastic meningiosis. J Neurooncol. 1998;38(2–3):111–20.CrossRefPubMed Schumacher M, Orszagh M. Imaging techniques in neoplastic meningiosis. J Neurooncol. 1998;38(2–3):111–20.CrossRefPubMed
24.
go back to reference Reiber H. Flow rate of cerebrospinal fluid (CSF)–a concept common to normal blood–CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci. 1994;122(2):189–203.CrossRefPubMed Reiber H. Flow rate of cerebrospinal fluid (CSF)–a concept common to normal blood–CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci. 1994;122(2):189–203.CrossRefPubMed
25.
go back to reference Kolodziej MA, Proemmel P, Quint K, Strik HM. Cerebrospinal fluid ferritin—unspecific and unsuitable for disease monitoring. Neurol Neurochir Pol. 2014;48:116–21.PubMed Kolodziej MA, Proemmel P, Quint K, Strik HM. Cerebrospinal fluid ferritin—unspecific and unsuitable for disease monitoring. Neurol Neurochir Pol. 2014;48:116–21.PubMed
26.
go back to reference Reiber H. Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases. Diagnostic patterns not to be missed in neurology and psychiatry. Arq Neuropsiquiatr. 2016;74:337–50.CrossRefPubMed Reiber H. Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases. Diagnostic patterns not to be missed in neurology and psychiatry. Arq Neuropsiquiatr. 2016;74:337–50.CrossRefPubMed
27.
go back to reference Wang P, Piao Y, Zhang X, Li W, Hao X. The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid can be useful indicators for diagnosis of meningeal carcinomatosis of lung cancer. Cancer Biomark. 2013;13:123–30.CrossRefPubMed Wang P, Piao Y, Zhang X, Li W, Hao X. The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid can be useful indicators for diagnosis of meningeal carcinomatosis of lung cancer. Cancer Biomark. 2013;13:123–30.CrossRefPubMed
Metadata
Title
Cerebrospinal fluid abnormalities in meningeosis neoplastica: a retrospective 12-year analysis
Authors
Marija Djukic
Ralf Trimmel
Ingelore Nagel
Annette Spreer
Peter Lange
Christine Stadelmann
Roland Nau
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2017
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-017-0057-2

Other articles of this Issue 1/2017

Fluids and Barriers of the CNS 1/2017 Go to the issue