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Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma

Abstract

Recent studies addressing the molecular characteristics of PCNSL, which is defined as malignant B-cell lymphoma with morphological features of DLBCL, have significantly improved our understanding of the pathogenesis of this lymphoma entity, which is associated with an inferior prognosis as compared with DLBCL outside the CNS. This unfavorable prognosis stimulated intense efforts to improve therapy and induced recent series of clinical studies, which addressed the role of radiotherapy and various chemotherapeutic regimens. This review combines the discussion of diagnosis, differential diagnosis and recent progress in studies addressing the molecular pathogenesis as well as therapeutic options in PCNSL.

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References

  1. Batchelor T, Loeffler JS . Primary CNS lymphoma. J Clin Oncol 2006; 24: 1281–1288.

    CAS  PubMed  Google Scholar 

  2. Küker W, Nägele T, Korfel A, Heckl S, Thiel E, Bamberg M et al. Primary central nervous system lymphomas (PCNSL): MRI features at presentation in 100 patients. J Neurooncol 2005; 72: 169–177.

    PubMed  Google Scholar 

  3. Jahnke K, Korfel A, Komm J, Bechrakis NE, Stein H, Thiel E et al. Intraocular lymphoma 2000–2005: results of a retrospective multicentre trial. Graefes Arch Clin Exp Ophthalmol 2006; 244: 663–669.

    PubMed  Google Scholar 

  4. Fischer L, Martus P, Weller M, Klasen HA, Rohden B, Roth A et al. Meningeal dissemination in primary CNS lymphoma: prospective evaluation of 282 patients. Neurology 2008; 71: 1102–1108.

    CAS  PubMed  Google Scholar 

  5. Coupland SE, Heimann H, Bechrakis NE . Primary intraocular lymphoma: a review of the clinical, histopathological and molecular biological features. Graefes Arch Clin Exp Ophthalmol 2004; 242: 901–913.

    PubMed  Google Scholar 

  6. Lachance DH, O'Neill BP, Macdonald DR, Jaeckle KA, Witzig TE, Li CY et al. Primary leptomeningeal lymphoma: report of 9 cases, diagnosis with immunocytochemical analysis, and review of the literature. Neurology 1991; 41: 95–100.

    CAS  PubMed  Google Scholar 

  7. Bellinzona M, Roser F, Ostertag H, Gaab RM, Saini M . Surgical removal of primary central nervous system lymphomas (PCNSL) presenting as space occupying lesions: a series of 33 cases. Eur J Surg Oncol 2005; 31: 100–105.

    CAS  PubMed  Google Scholar 

  8. Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W et al. Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 2006; 24: 5711–5715.

    PubMed  Google Scholar 

  9. Ferreri AJ, Blay JY, Reni M, Pasini F, Spina M, Ambrosetti A et al. Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncol 2003; 21: 266–272.

    PubMed  Google Scholar 

  10. Deckert-Schlüter M, Rang A, Wiestler OD . Apoptosis and apoptosis-related gene products in primary non-Hodgkin's lymphoma of the central nervous system. Acta Neuropathol 1998; 96: 157–162.

    PubMed  Google Scholar 

  11. Klapper W, Wacker HH . Follicular and mantle cell lymphoma. Extranodal involvement of primarily nodal indolent B-cell lymphomas. Pathologe 2007; 28: 21–28.

    CAS  PubMed  Google Scholar 

  12. Hollender A, Kvaloy S, Nome O, Skovlund E, Lote K, Holte H . Central nervous system involvement following diagnosis of non-Hodgkin's lymphoma: a risk model. Ann Oncol 2002; 13: 1099–1107.

    CAS  PubMed  Google Scholar 

  13. Salzburg J, Burkhardt B, Zimmermann M, Wachowski O, Woessmann W, Oschlies I et al. Prevalence, clinical pattern, and outcome of CNS involvement in childhood and adolescent non-Hodgkin's lymphoma differ by non-Hodgkin's lymphoma subtype: a Berlin–Frankfurt–Munster Group Report. J Clin Oncol 2007; 25: 3915–3922.

    PubMed  Google Scholar 

  14. Palmieri C, Treibel T, Large O, Bower M . AIDS-related non-Hodgkin's lymphoma in the first decade of highly active antiretroviral therapy. QJM 2006; 99: 811–826.

    CAS  PubMed  Google Scholar 

  15. Schweikert A, Kremer M, Ringel F, Liebig T, Duyster J, Stuve O et al. Primary central nervous system lymphoma in a patient treated with natalizumab. Ann Neurol 2009; 66: 403–406.

    CAS  PubMed  Google Scholar 

  16. Lucantoni C, De Bonis P, Doglietto F, Esposito G, Larocca LM, Mangiola A et al. Primary cerebral lymphomatoid granulomatosis: report of four cases and literature review. J Neurooncol 2009; 94: 235–242.

    PubMed  Google Scholar 

  17. Kumar S, Kumar D, Kaldjian EP, Bauserman S, Raffeld M, Jaffe ES . Primary low-grade B-cell lymphoma of the dura: a mucosa associated lymphoid tissue-type lymphoma. Am J Surg Pathol 1997; 21: 81–87.

    CAS  PubMed  Google Scholar 

  18. Deckert M, Paulus W . Malignant lymphomas. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds) WHO Classification of Tumors Pathology & Genetics of Tumours of the Nervous System, 4th edn. IRAC: Lyon, 2007, pp 188–192.

    Google Scholar 

  19. Shenkier TN, Blay JY, O'Neill BP, Poortmans P, Thiel E, Jahnke K et al. Primary CNS lymphoma of T-cell origin: a descriptive analysis from the international primary CNS lymphoma collaborative group. J Clin Oncol 2005; 23: 2233–2239.

    PubMed  Google Scholar 

  20. Wanschitz J, Hainfellner JA, Simonitsch I, Schnizer M, Deisenhammer E, Terunuma H et al. Non-HTLV-I associated pleomorphic T-cell lymphoma of the brain mimicking post-vaccinal acute inflammatory demyelination. Neuropathol Appl Neurobiol 1997; 23: 43–49.

    CAS  PubMed  Google Scholar 

  21. Grois N, Prayer D, Prosch H, Lassmann H . Neuropathology of CNS disease in Langerhans cell histiocytosis. Brain 2005; 128 (Part 4): 829–838.

    PubMed  Google Scholar 

  22. Kuhlmann T, Lassmann H, Brück W . Diagnosis of inflammatory demyelination in biopsy specimens: a practical approach. Acta Neuropathol 2008; 115: 275–287.

    PubMed  PubMed Central  Google Scholar 

  23. Hajj-Ali RA, Calabrese LH . Central nervous system vasculitis. Curr Opin Rheumatol 2009; 21: 10–18.

    PubMed  Google Scholar 

  24. Montesinos-Rongen M, Zühlke-Jenisch R, Gesk S, Martin-Subero JI, Schaller C, Van Roost D et al. Interphase cytogenetic analysis of lymphoma-associated chromosomal breakpoints in primary diffuse large B-cell lymphomas of the central nervous system. J Neuropathol Exp Neurol 2002; 61: 926–933.

    CAS  PubMed  Google Scholar 

  25. Montesinos-Rongen M, Van Roost D, Schaller C, Wiestler OD, Deckert M . Primary diffuse large B-cell lymphomas of the central nervous system are targeted by aberrant somatic hypermutation. Blood 2004; 103: 1869–1875.

    CAS  PubMed  Google Scholar 

  26. Courts C, Montesinos-Rongen M, Brunn A, Bug S, Siemer D, Hans V et al. Recurrent inactivation of the PRDM1 gene in primary central nervous system lymphoma. J Neuropathol Exp Neurol 2008; 67: 720–727.

    CAS  PubMed  Google Scholar 

  27. Schwindt H, Vater I, Kreuz M, Montesinos-Rongen M, Brunn A, Richter J et al. Chromosomal imbalances and partial uniparental disomies in primary central nervous system lymphoma. Leukemia 2009; 23: 1875–1884.

    CAS  PubMed  Google Scholar 

  28. Courts C, Montesinos-Rongen M, Martin-Subero JI, Brunn A, Siemer D, Zühlke-Jenisch R et al. Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression. J Neuropathol Exp Neurol 2007; 66: 230–237.

    CAS  PubMed  Google Scholar 

  29. Montesinos-Rongen M, Schmitz R, Brunn A, Gesk S, Richter J, Hong K et al. Mutations of CARD11 but not TNFAIP3 may activate the NF-kappaB pathway in primary CNS lymphoma. Acta Neuropathol 2010; 120: 529–535.

    CAS  PubMed  Google Scholar 

  30. Compagno M, Lim WK, Grunn A, Nandula SV, Brahmachary M, Shen Q et al. Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature 2009; 459: 717–721.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K et al. Frequent inactivation of A20 in B-cell lymphomas. Nature 2009; 459: 712–716.

    CAS  PubMed  Google Scholar 

  32. Booman M, Szuhai K, Rosenwald A, Hartmann E, Kluin-Nelemans H, de Jong D et al. Genomic alterations and gene expression in primary diffuse large B-cell lymphomas of immune-privileged sites: the importance of apoptosis and immunomodulatory pathways. J Pathol 2008; 216: 209–217.

    CAS  PubMed  Google Scholar 

  33. Montesinos-Rongen M, Brunn A, Bentink S, Basso K, Lim WK, Klapper W et al. Gene expression profiling suggests primary central nervous system lymphomas to be derived from a late germinal center B cell. Leukemia 2008; 22: 400–405.

    CAS  PubMed  Google Scholar 

  34. Rubenstein JL, Fridlyand J, Shen A, Aldape K, Ginzinger D, Batchelor T et al. Gene expression and angiotropism in primary CNS lymphoma. Blood 2006; 107: 3716–3723.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Tun HW, Personett D, Baskerville KA, Menke DM, Jaeckle KA, Kreinest P et al. Pathway analysis of primary central nervous system lymphoma. Blood 2008; 111: 3200–3210.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Chu LC, Eberhart CG, Grossman SA, Herman JG . Epigenetic silencing of multiple genes in primary CNS lymphoma. Int J Cancer 2006; 119: 2487–2491.

    CAS  PubMed  Google Scholar 

  37. Cobbers JM, Wolter M, Reifenberger J, Ring GU, Jessen F, An HX et al. Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL. Brain Pathol 1998; 8: 263–276.

    CAS  PubMed  Google Scholar 

  38. Ferreri AJ, Dell'Oro S, Capello D, Ponzoni M, Iuzzolino P, Rossi D et al. Aberrant methylation in the promoter region of the reduced folate carrier gene is a potential mechanism of resistance to methotrexate in primary central nervous system lymphomas. Br J Haematol 2004; 126: 657–664.

    CAS  PubMed  Google Scholar 

  39. Richter J, Ammerpohl O, Martin-Subero JI, Montesinos-Rongen M, Bibikova M, Wickham-Garcia E et al. Array-based DNA methylation profiling of primary lymphomas of the central nervous system. BMC Cancer 2009; 9: 455–462.

    PubMed  PubMed Central  Google Scholar 

  40. Martinez-Climent JA, Fontan L, Gascoyne RD, Siebert R, Prosper F . Lymphoma stem cells: enough evidence to support their existence? Haematologica 2010; 95: 293–302.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Montesinos-Rongen M, Küppers R, Schlüter D, Spieker T, Van Roost D, Schaller C et al. Primary central nervous system lymphomas are derived from germinal-center B cells and show a preferential usage of the V4-34 gene segment. Am J Pathol 1999; 155: 2077–2086.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Thompsett AR, Ellison DW, Stevenson FK, Zhu D . V(H) gene sequences from primary central nervous system lymphomas indicate derivation from highly mutated germinal center B cells with ongoing mutational activity. Blood 1999; 94: 1738–1746.

    CAS  PubMed  Google Scholar 

  43. Pugh-Bernard AE, Silverman GJ, Cappione AJ, Villano ME, Ryan DH, Insel RA et al. Regulation of inherently autoreactive VH4-34 B cells in the maintenance of human B cell tolerance. J Clin Invest 2001; 108: 1061–1070.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Booman M, Douwes J, Legdeur MC, van Baarlen J, Schuuring E, Kluin P . From brain to testis: immune escape and clonal selection in a B cell lymphoma with selective outgrowth in two immune sanctuaries. Haematologica 2007; 92: e69–e71.

    PubMed  Google Scholar 

  45. Pels H, Montesinos-Rongen M, Schaller C, Van Roost D, Schlegel U, Wiestler OD et al. Clonal evolution as pathogenetic mechanism in relapse of primary CNS lymphoma. Neurology 2004; 63: 167–169.

    CAS  PubMed  Google Scholar 

  46. Jahnke K, Hummel M, Korfel A, Burmeister T, Kiewe P, Klasen HA et al. Detection of subclinical systemic disease in primary CNS lymphoma by polymerase chain reaction of the rearranged immunoglobulin heavy-chain genes. J Clin Oncol 2006; 24: 4754–4757.

    CAS  PubMed  Google Scholar 

  47. McCann KJ, Ashton-Key M, Smith K, Stevenson FK, Ottensmeier CH . Primary central nervous system lymphoma: tumor-related clones exist in the blood and bone marrow with evidence for separate development. Blood 2009; 113: 4677–4680.

    CAS  PubMed  Google Scholar 

  48. Seifert M, Küppers R . Molecular footprints of a germinal center derivation of human IgM+(IgD+)CD27+ B cells and the dynamics of memory B cell generation. J Exp Med 2009; 206: 2659–2669.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Brunn A, Montesinos-Rongen M, Strack A, Reifenberger G, Mawrin C, Schaller C et al. Expression pattern and cellular sources of chemokines in primary central nervous system lymphoma. Acta Neuropathol (Berl) 2007; 114: 271–276.

    CAS  Google Scholar 

  50. Paulus W, Jellinger K . Comparison of integrin adhesion molecules expressed by primary brain lymphomas and nodal lymphomas. Acta Neuropathol 1993; 86: 360–364.

    CAS  PubMed  Google Scholar 

  51. Riemersma SA, Jordanova ES, Schop RF, Philippo K, Looijenga LH, Schuuring E et al. Extensive genetic alterations of the HLA region, including homozygous deletions of HLA class II genes in B-cell lymphomas arising in immune-privileged sites. Blood 2000; 96: 3569–3577.

    CAS  PubMed  Google Scholar 

  52. Schlüter D, Löhler J, Deckert M, Hof H, Schwendemann G . Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical characterisation of Toxoplasma antigen, infiltrates and major histocompatibility complex gene products. J Neuroimmunol 1991; 31: 185–198.

    PubMed  Google Scholar 

  53. Abrey LE, DeAngelis LM, Yahalom J . Long-term survival in primary CNS lymphoma. J Clin Oncol 1998; 16: 859–863.

    CAS  PubMed  Google Scholar 

  54. Abrey LE, Yahalom J, DeAngelis LM . Treatment for primary CNS lymphoma: the next step. J Clin Oncol 2000; 18: 3144–3150.

    CAS  PubMed  Google Scholar 

  55. Batchelor T, Carson K, O’Neill A, Grossman SA, Alavi J, New P et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol 2003; 21: 1044–1049.

    CAS  PubMed  Google Scholar 

  56. Bessell EM, Lopez-Guillermo A, Villa S, Verger E, Nomdedeu B, Petit J et al. Importance of radiotherapy in the outcome of patients with primary CNS lymphoma: an analysis of the CHOD/BVAM regimen followed by two different radiotherapy treatments. J Clin Oncol 2002; 20: 231–236.

    CAS  PubMed  Google Scholar 

  57. Blay JY, Bouhour D, Carrie C, Bouffet E, Brunat-Mentigny M, Philip T et al. The C5R protocol: a regimen of high-dose chemotherapy and radiotherapy in primary cerebral non-Hodgkin's lymphoma of patients with no known cause of immunosuppression. Blood 1995; 86: 2922–2929.

    CAS  PubMed  Google Scholar 

  58. Brada M, Hjiyiannakis D, Hines F, Traish D, Ashley S . Short intensive primary chemotherapy and radiotherapy in sporadic primary CNS lymphoma (PCL). Int J Radiat Oncol Biol Phys 1998; 40: 1157–1162.

    CAS  PubMed  Google Scholar 

  59. DeAngelis LM, Seiferheld W, Schold SC, Fisher B, Schultz CJ . Combination chemotherapy and radiotherapy for primary central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol 2002; 20: 4643–4648.

    PubMed  Google Scholar 

  60. Ferreri AJ, Dell'Oro S, Foppoli M, Bernardi M, Brandes AA, Tosoni A et al. MATILDE regimen followed by radiotherapy is an active strategy against primary CNS lymphomas. Neurology 2006; 66: 1435–1438.

    CAS  PubMed  Google Scholar 

  61. Ferreri AJ, Reni M, Pasini F, Calderoni A, Tirelli U, Pivnik A et al. A multicenter study of treatment of primary CNS lymphoma. Neurology 2002; 58: 1513–1520.

    CAS  PubMed  Google Scholar 

  62. Glass J, Gruber ML, Cher L, Hochberg FH . Preirradiation methotrexate chemotherapy of primary central nervous system lymphoma: long-term outcome. J Neurosurg 1994; 81: 188–195.

    CAS  PubMed  Google Scholar 

  63. Guha-Thakurta N, Damek D, Pollack C, Hochberg FH . Intravenous methotrexate as initial treatment for primary central nervous system lymphoma: response to therapy and quality of life of patients. J Neurooncol 1999; 43: 259–268.

    CAS  PubMed  Google Scholar 

  64. Herrlinger U, Kuker W, Uhl M, Blaicher HP, Karnath HO, Kanz L et al. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann Neurol 2005; 57: 843–847.

    CAS  PubMed  Google Scholar 

  65. Hoang-Xuan K, Taillandier L, Chinot O, Soubeyran P, Bogdhan U, Hildebrand J et al. Chemotherapy alone as initial treatment for primary CNS lymphoma in patients older than 60 years: a multicenter phase II study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group. J Clin Oncol 2003; 21: 2726–2731.

    CAS  PubMed  Google Scholar 

  66. Korfel A, Thiel E . Successful treatment of non-Hodgkin's lymphoma of the central nervous system with BMPD chemotherapy followed by radiotherapy. Leuk Lymphoma 1998; 30: 609–617.

    CAS  PubMed  Google Scholar 

  67. O’Brien PC, Roos DE, Pratt G, Liew KH, Barton MB, Poulsen MG et al. Combined-modality therapy for primary central nervous system lymphoma: long-term data from a phase II multicenter study (Trans-Tasman Radiation Oncology Group). Int J Radiat Oncol Biol Phys 2006; 64: 408–413.

    PubMed  Google Scholar 

  68. Pels H, Schmidt-Wolf IG, Glasmacher A, Schulz H, Engert A, Diehl V et al. Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy. J Clin Oncol 2003; 21: 4489–4495.

    CAS  PubMed  Google Scholar 

  69. Poortmans PM, Kluin-Nelemans HC, Haaxma-Reiche H, Van’t Veer M, Hansen M, Soubeyran P et al. High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962. J Clin Oncol 2003; 21: 4483–4488.

    CAS  PubMed  Google Scholar 

  70. Reni M, Ferreri AJ, Guha-Thakurta N, Blay JY, Dell'Oro S, Biron P et al. Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate. Int J Radiat Oncol Biol Phys 2001; 51: 419–425.

    CAS  PubMed  Google Scholar 

  71. Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol 2007; 25: 4730–4735.

    CAS  PubMed  Google Scholar 

  72. Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M et al. High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet 2009; 374: 1512–1520.

    CAS  PubMed  Google Scholar 

  73. Thiel E, Korfel A, Martus P, Kanz L, Griesinger F, Rauch M et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol 2010; 11: 1036–1047.

    CAS  PubMed  Google Scholar 

  74. Mead GM, Bleehen NM, Gregor A, Bullimore J, Shirley D, Rampling RP et al. A medical research council randomized trial in patients with primary cerebral non-Hodgkin lymphoma: cerebral radiotherapy with and without cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. Cancer 2000; 89: 1359–1370.

    CAS  PubMed  Google Scholar 

  75. Porter AB, Giannini C, Kaufmann T, Lucchinetti CF, Wu W, Decker PA et al. Primary central nervous system lymphoma can be histologically diagnosed after previous corticosteroid use: a pilot study to determine whether corticosteroids prevent the diagnosis of primary central nervous system lymphoma. Ann Neurol 2008; 63: 662–667.

    CAS  PubMed  Google Scholar 

  76. Nelson DF, Martz KL, Bonner H, Nelson JS, Newall J, Kerman HD et al. Non-Hodgkin's lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys 1992; 23: 9–17.

    CAS  PubMed  Google Scholar 

  77. Shibamoto Y, Ogino H, Hasegawa M, Suzuki K, Nishio M, Fujii T et al. Results of radiation monotherapy for primary central nervous system lymphoma in the 1990s. Int J Radiat Oncol Biol Phys 2005; 62: 809–813.

    PubMed  Google Scholar 

  78. Feugier P, Virion JM, Tilly H, Haioun C, Marit G, Macro M et al. Incidence and risk factors for central nervous system occurrence in elderly patients with diffuse large-B-cell lymphoma: influence of rituximab. Ann Oncol 2004; 15: 129–133.

    CAS  PubMed  Google Scholar 

  79. Glass J, Shustik C, Hochberg FH, Cher L, Gruber ML . Therapy of primary central nervous system lymphoma with pre-irradiation methotrexate, cyclophosphamide, doxorubicin, vincristine, and dexamethasone (MCHOD). J Neurooncol 1996; 30: 257–265.

    CAS  PubMed  Google Scholar 

  80. Hottinger AF, DeAngelis LM, Yahalom J, Abrey LE . Salvage whole brain radiotherapy for recurrent or refractory primary CNS lymphoma. Neurology 2007; 69: 1178–1182.

    PubMed  Google Scholar 

  81. Nguyen PL, Chakravarti A, Finkelstein DM, Hochberg FH, Batchelor TT, Loeffler JS . Results of whole-brain radiation as salvage of methotrexate failure for immunocompetent patients with primary CNS lymphoma. J Clin Oncol 2005; 23: 1507–1513.

    PubMed  Google Scholar 

  82. Borsi JD, Moe PJ . A comparative study on the pharmacokinetics of methotrexate in a dose range of 0.5 g–33.6 g/m2 in children with acute lymphoblastic leukemia. Cancer 1987; 60: 5–13.

    CAS  PubMed  Google Scholar 

  83. Shapiro WR, Young DF, Mehta BM . Methotrexate: distribution in cerebrospinal fluid after intravenous, ventricular and lumbar injections. N Engl J Med 1975; 293: 161–166.

    CAS  PubMed  Google Scholar 

  84. Angelov L, Doolittle ND, Kraemer DF, Siegal T, Barnett GH, Peereboom DM et al. Blood-brain barrier disruption and intra-arterial methotrexate-based therapy for newly diagnosed primary CNS lymphoma: a multi-institutional experience. J Clin Oncol 2009; 27: 3503–3509.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Weller M . Glucocorticoid treatment of primary CNS lymphoma. J Neurooncol 1999; 43: 237–239.

    CAS  PubMed  Google Scholar 

  86. Reni M, Zaja F, Mason W, Perry J, Mazza E, Spina M et al. Temozolomide as salvage treatment in primary brain lymphomas. Br J Cancer 2007; 96: 864–867.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Fischer L, Thiel E, Klasen HA, Birkmann J, Jahnke K, Martus P et al. Prospective trial on topotecan salvage therapy in primary CNS lymphoma. Ann Oncol 2006; 17: 1141–1145.

    CAS  PubMed  Google Scholar 

  88. Juergens A, Pels H, Rogowski S, Fliessbach K, Glasmacher A, Engert A et al. Long-term survival with favorable cognitive outcome after chemotherapy in primary central nervous system lymphoma. Ann Neurol 2010; 67: 182–189.

    CAS  PubMed  Google Scholar 

  89. Pels H, Juergens A, Schirgens I, Glasmacher A, Schulz H, Engert A et al. Early complete response during chemotherapy predicts favorable outcome in patients with primary CNS lymphoma. Neuro Oncol 2010; 12: 720–724.

    PubMed  PubMed Central  Google Scholar 

  90. Khan RB, Shi W, Thaler HT, DeAngelis LM, Abrey LE . Is intrathecal methotrexate necessary in the treatment of primary CNS lymphoma? J Neurooncol 2002; 58: 175–178.

    PubMed  Google Scholar 

  91. Soussain C, Suzan F, Hoang-Xuan K, Cassoux N, Levy V, Azar N et al. Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma. J Clin Oncol 2001; 19: 742–749.

    CAS  PubMed  Google Scholar 

  92. Abrey LE, Moskowitz CH, Mason WP, Crump M, Stewart D, Forsyth P et al. Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis. J Clin Oncol 2003; 21: 4151–4156.

    CAS  PubMed  Google Scholar 

  93. Ferreri AJ, Abrey LE, Blay JY, Borisch B, Hochman J, Neuwelt EA et al. Summary statement on primary central nervous system lymphomas from the Eighth International Conference on Malignant Lymphoma, Lugano, Switzerland, June 12 to 15, 2002. J Clin Oncol 2003; 21: 2407–2414.

    PubMed  Google Scholar 

  94. Illerhaus G, Marks R, Ihorst G, Guttenberger R, Ostertag C, Derigs G et al. High-dose chemotherapy with autologous stem-cell transplantation and hyperfractionated radiotherapy as first-line treatment of primary CNS lymphoma. J Clin Oncol 2006; 24: 3865–3870.

    CAS  PubMed  Google Scholar 

  95. Omuro AM, Ben-Porat LS, Panageas KS, Kim AK, Correa DD, Yahalom J et al. Delayed neurotoxicity in primary central nervous system lymphoma. Arch Neurol 2005; 62: 1595–1600.

    PubMed  Google Scholar 

  96. Correa DD, Maron L, Harder H, Klein M, Armstrong CL, Calabrese P et al. Cognitive functions in primary central nervous system lymphoma: literature review and assessment guidelines. Ann Oncol 2007; 18: 1145–1151.

    CAS  PubMed  Google Scholar 

  97. Colombat P, Lemevel A, Bertrand P, Delwail V, Rachieru P, Brion A et al. High-dose chemotherapy with autologous stem cell transplantation as first-line therapy for primary CNS lymphoma in patients younger than 60 years: a multicenter phase II study of the GOELAMS group. Bone Marrow Transplant 2006; 38: 417–420.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The paper summarizes data discussed on the occasion of the NLLLN Meeting Primary CNS Lymphoma—Neuropathology & Differential Diagnosis—Biology & Genetics held in Cologne, 15 January 2010. NLLLN is member of KML. This study was supported by the Deutsche Krebshilfe/Dr Mildred Scheel Stiftung für Krebsforschung (Grant no. 109471) and the Deutsche Forschungsgemeinschaft (De 485/9-1).

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Deckert, M., Engert, A., Brück, W. et al. Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma. Leukemia 25, 1797–1807 (2011). https://doi.org/10.1038/leu.2011.169

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