title: Lymphomatosis cerebri: a rare form of primary central nervous system lymphoma. Analysis of 7 cases and systematic review of the literature.
abstract: Primary central nervous system lymphomas may present as diffuse, nonenhancing infiltrative lesions. This rare variant is termed lymphomatosis cerebri (LC). We did a systematic review and analysis of the literature, adding our own cases, to better characterize LC in order to improve early diagnosis and treatment.
  
  
  
  PubMed, ISI Web of Knowledge, and hospital databases were reviewed. Information was extracted regarding demographic, clinical, histological, cerebrospinal fluid (CSF), neuroimaging, and treatment variables. The impact of single parameters on overall survival (OS) was determined by applying univariate and multivariate analyses.
  
  
  
  Forty-two patients were included (median age: 58 y; range: 28-80 y). At consultation, 52% of patients had a poor KPS. The most common presenting symptom was cognitive decline (59.5%). Imaging studies showed supratentorial and infratentorial infiltration in 55% of patients and bilateral hemispheric involvement in 95%. CSF pleocytosis was present in 51.5% of the patients. Median time to diagnosis was 4.5 (range: 1-30) months, and the diagnosis was not established until autopsy for 33% of patients. The median OS was 2.95 (range: 0.33-56) months; however, those patients who received methotrexate had a median OS of 13.8 (range: 0.7-56) months. Analysis identified KPS ≥ 70 (HR: 0.32; 95% CI: 0.114-0.894; P = .03) and treatment with methotrexate (HR: 0.19; 95% CI: 0.041-0.886; P = .034) as independent favorable prognostic factors, whereas T-cell lymphoma was independently related with a worse outcome (HR: 6.62; 95% CI: 1.317-33.316; P = .022).
  
  
  
  LC is a misdiagnosed entity associated with considerable diagnostic delay. MRI evidence of bilateral hemispheric involvement and CSF pleocytosis should be alerts for this diagnosis. Treatment with methotrexate-based chemotherapy must be considered, especially for patients with good KPS.
authors.affiliation: Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (C.I., R.V., N.V., S.B., J.B.); Department Cell Biology, Institute of Neurosciences, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain (R.V., J.B.); Department of Radiology, Institut de Diagnòstic per la Imatge, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (J.J.S.); Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece (A.A.A.); Service of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain (F.G.).
authors.forename: Cristina
authors.initials: C
authors.lastname: Izquierdo
authors.affiliation: Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (C.I., R.V., N.V., S.B., J.B.); Department Cell Biology, Institute of Neurosciences, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain (R.V., J.B.); Department of Radiology, Institut de Diagnòstic per la Imatge, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (J.J.S.); Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece (A.A.A.); Service of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain (F.G.).
authors.forename: Roser
authors.initials: R
authors.lastname: Velasco
authors.affiliation: Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (C.I., R.V., N.V., S.B., J.B.); Department Cell Biology, Institute of Neurosciences, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain (R.V., J.B.); Department of Radiology, Institut de Diagnòstic per la Imatge, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (J.J.S.); Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece (A.A.A.); Service of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain (F.G.).
authors.forename: Noemí
authors.initials: N
authors.lastname: Vidal
authors.affiliation: Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (C.I., R.V., N.V., S.B., J.B.); Department Cell Biology, Institute of Neurosciences, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain (R.V., J.B.); Department of Radiology, Institut de Diagnòstic per la Imatge, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (J.J.S.); Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece (A.A.A.); Service of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain (F.G.).
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Sánchez
authors.affiliation: Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (C.I., R.V., N.V., S.B., J.B.); Department Cell Biology, Institute of Neurosciences, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain (R.V., J.B.); Department of Radiology, Institut de Diagnòstic per la Imatge, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (J.J.S.); Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece (A.A.A.); Service of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain (F.G.).
authors.forename: Andreas A
authors.initials: AA
authors.lastname: Argyriou
authors.affiliation: Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (C.I., R.V., N.V., S.B., J.B.); Department Cell Biology, Institute of Neurosciences, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain (R.V., J.B.); Department of Radiology, Institut de Diagnòstic per la Imatge, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (J.J.S.); Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece (A.A.A.); Service of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain (F.G.).
authors.forename: Sarah
authors.initials: S
authors.lastname: Besora
authors.affiliation: Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (C.I., R.V., N.V., S.B., J.B.); Department Cell Biology, Institute of Neurosciences, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain (R.V., J.B.); Department of Radiology, Institut de Diagnòstic per la Imatge, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (J.J.S.); Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece (A.A.A.); Service of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain (F.G.).
authors.forename: Francesc
authors.initials: F
authors.lastname: Graus
authors.affiliation: Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (C.I., R.V., N.V., S.B., J.B.); Department Cell Biology, Institute of Neurosciences, Physiology and Immunology, Universitat Autònoma de Barcelona, and Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Bellaterra, Spain (R.V., J.B.); Department of Radiology, Institut de Diagnòstic per la Imatge, Hospital Universitari de Bellvitge-ICO Duran i Reynals, Barcelona, Spain (J.J.S.); Department of Neurology, St. Andrew's State General Hospital of Patras, Patras, Greece (A.A.A.); Service of Neurology, Hospital Clínic de Barcelona, Barcelona, Spain (F.G.).
authors.forename: Jordi
authors.initials: J
authors.lastname: Bruna
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D016543:Central Nervous System Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008223:Lymphoma / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011878:Radiotherapy
chemical_list: D000970:Antineoplastic Agents
keywords: diffuse infiltrative lesion; leukoencephalopathy; lymphomatosis cerebri; primary central nervous system lymphoma