Journal of Neuro-Oncology

, Volume 121, Issue 1, pp 177–183 | Cite as

Diagnostic value of interleukin-10 in cerebrospinal fluid for diffuse large B-cell lymphoma of the central nervous system

  • Yasuo Sasagawa
  • Takuya Akai
  • Osamu Tachibana
  • Hideaki Iizuka
Clinical Study


A biomarker for early diagnosis of central nervous system (CNS) lymphoma would permit early treatment for attenuation of disease progression and neurological deterioration. High interleukin-10 (IL-10) or an IL-10/IL-6 ratio >1.0 are informative parameters for discriminating intraocular lymphomas from uveitis. Recent reports have also shown that CSF IL-10 is a potential diagnostic biomarker for CNS lymphoma. The purpose of this study was to evaluate the diagnostic value of IL-10 in cerebrospinal fluid (CSF) in patients with CNS lymphoma compared with other CNS diseases, including CNS tumors and inflammatory diseases. CSF IL-10, IL-6, beta-2 microglobulin, soluble IL-2 receptor and FDG-PET SUVmax were measured in 19 patients with CNS lymphoma (15 primary and 4 secondary diffuse large B-cell lymphomas) and 26 non-lymphoma patients with various brain tumors and inflammatory diseases. The diagnostic accuracy of the respective examinations for differentiation of CNS lymphomas from non-lymphomas was evaluated by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve (AUC) was calculated. CSF IL-10 was detected at significant levels (median, 28 pg/ml; range <2–4,100 pg/ml) in all except one patient with CNS lymphoma, but not detected in any non-lymphoma patients. CSF IL-10 had the highest diagnostic accuracy with AUC = 0.974. At an IL-10 cutoff of 3 pg/ml, the sensitivity and specificity were 94.7 and 100 %, respectively. These results indicate that CSF IL-10 is a superior biomarker for initial screening for patients with CNS lymphoma.


Central nervous system lymphoma Diffuse large B-cell lymphoma Interleukin-10 Cerebrospinal fluid Sensitivity Specificity 



This work was supported by a Grant for Promoted Research from Kanazawa Medical University (S2013-7).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Olson JE, Janney CA, Rao RD, Cerhan JR, Kurtin PJ, Schiff D, Kaplan RS, O’Neill BP (2002) The continuing increase in the incidence of primary central nervous system non-Hodgkin lymphoma: a surveillance, epidemiology, and end results analysis. Cancer 95:1504–1510PubMedCrossRefGoogle Scholar
  2. 2.
    Pels H, Juergens A, Schirgens I, Glasmacher A, Schulz H, Engert A, Schackert G, Reichmann H, Kroschinsky F, Vogt-Schaden M, Egerer G, Bode U, Deckert M, Fimmers R, Urbach H, Schmidt-Wolf IG, Schlegel U (2010) Early complete response during chemotherapy predicts favorable outcome in patients with primary CNS lymphoma. Neuro Oncol 12:720–724PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Kosaka N, Tsuchida T, Uematsu H, Kimura H, Okazawa H, Itoh H (2008) 18F-FDG PET of common enhancing malignant brain tumors. AJR Am J Roentgenol 190:365–369CrossRefGoogle Scholar
  4. 4.
    Yamashita K, Yoshiura T, Hiwatashi A, Togao O, Yoshimoto K, Suzuki SO, Abe K, Kikuchi K, Maruoka Y, Mizoguchi M, Iwaki T, Honda H (2013) Differentiating primary CNS lymphoma from glioblastoma multiforme: assessment using arterial spin labeling, diffusion-weighted imaging, and 18F-fluorodeoxyglucose positron emission tomography. Neuroradiology 55:135–143PubMedCrossRefGoogle Scholar
  5. 5.
    Scott BJ, Douglas VC, Tihan T, Rubenstein JL, Josephson SA (2013) A systematic approach to the diagnosis of suspected central nervous system lymphoma. JAMA Neurol 70:311–319PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Cassoux N, Giron A, Bodaghi B, Tran TH, Baudet S, Davy F, Chan CC, Lehoang P, Merle-Béral H (2007) IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma. Investig Ophthalmol Vis Sci 48:3253–3259CrossRefGoogle Scholar
  7. 7.
    Cassoux N, Merle-Beral H, Leblond V, Bodaghi B, Miléa D, Gerber S, Fardeau C, Reux I, Xuan KH, Chan CC, LeHoang P (2000) Ocular and central nervous system lymphoma: clinical features and diagnosis. Ocul Immunol Inflamm 8:243–250PubMedCrossRefGoogle Scholar
  8. 8.
    Kimura K, Usui Y, Goto H; Japanese Intraocular Lymphoma Study Group (2012) Clinical features and diagnostic significance of the intraocular fluid of 217 patients with intraocular lymphoma. Jpn J Ophthalmol 56:383–389CrossRefGoogle Scholar
  9. 9.
    Wolf LA, Reed GF, Buggage RR, Nussenblatt RB, Chan CC (2003) Vitreous cytokine levels. Ophthalmology 110:1671–1672PubMedCrossRefGoogle Scholar
  10. 10.
    Chan CC, Buggage RR, Nussenblatt RB (2002) Intraocular lymphoma. Curr Opin Ophthalmol 13:411–418PubMedCrossRefGoogle Scholar
  11. 11.
    Chan CC (2003) Molecular pathology of primary intraocular lymphoma. Trans Am Ophthalmol Soc 101:275–292PubMedPubMedCentralGoogle Scholar
  12. 12.
    Sasayama T, Nakamizo S, Nishihara M, Kawamura A, Tanaka H, Mizukawa K, Miyake S, Taniguchi M, Hosoda K, Kohmura E (2012) Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL). Neuro Oncol 14:368–380PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Rubenstein JL, Wong VS, Kadoch C, Gao HX, Barajas R, Chen L, Josephson SA, Scott B, Douglas V, Maiti M, Kaplan LD, Treseler PA, Cha S, Hwang JH, Cinque P, Cyster JG, Lowell C (2013) CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood 121:4740–4748PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39:561–577PubMedGoogle Scholar
  15. 15.
    Branscum AJ, Gardner IA, Johnson WO (2005) Estimation of diagnostic-test sensitivity and specificity through Bayesian modeling. Prev Vet Med 68:145–163PubMedCrossRefGoogle Scholar
  16. 16.
    Trojano M, Paolicelli D (2001) The differential diagnosis of multiple sclerosis: classification and clinical features of relapsing and progressive neurological syndromes. Neurol Sci 22(Suppl 2):98–102CrossRefGoogle Scholar
  17. 17.
    Spencer TS, Campellone JV, Maldonado I, Huang N, Usmani Q, Reginato AJ (2005) Clinical and magnetic resonance imaging manifestations of neurosarcoidosis. Semin Arthritis Rheum 34:649–661PubMedCrossRefGoogle Scholar
  18. 18.
    Li N, Grivennikov SI, Karin M (2011) The unholy trinity: inflammation, cytokines, and STAT3 shape the cancer microenvironment. Cancer Cell 19:429–431PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    O’Garra A, Stapleton G, Dhar V, Pearce M, Schumacher J, Rugo H, Barbis D, Stall A, Cupp J, Moore K (1990) Production of cytokines by mouse B cells: b lymphomas and normal B cells produce interleukin 10. Int Immunol 2:821–832PubMedCrossRefGoogle Scholar
  20. 20.
    Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765PubMedCrossRefGoogle Scholar
  21. 21.
    McGuire TR, Brusnahan SK, Bilek LD, Jackson JD, Kessinger MA, Berger AM, Garvin KL, O’Kane BJ, Tuljapurkar SR, Sharp JG (2011) Inflammation associated with obesity: relationship with blood and bone marrow endothelial cells. Obesity (Silver Spring) 19:2130–2136CrossRefGoogle Scholar
  22. 22.
    Spits H, de Waal Malefyt R (1992) Functional characterization of human IL-10. Int Arch Allergy Immunol 99:8–15PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yasuo Sasagawa
    • 1
  • Takuya Akai
    • 1
  • Osamu Tachibana
    • 1
  • Hideaki Iizuka
    • 1
  1. 1.Department of NeurosurgeryKanazawa Medical UniversityUchinadaJapan

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