Primary Central Nervous System Lymphomas in 72 Immunocompetent Patients: Pathologic Findings and Clinical Correlations

Camilleri-Broët, Sophie; Martin, Antoine; Moreau, Anne; Angonin, R.; Hénin, Dominique; Gontier, M.-F.; Rousselet, Marie Christine; Caulet‐Maugendre, Sylvie; Cuillière, P; Lefrancq, Thierry; Mokhtari, Karima; Morcos, Mohib; Broët, Philippe; Kujas, M.; Hauw, Jean‐Jacques; Desablens, B; Raphaël, Martine

doi:10.1093/ajcp/110.5.607

Cited by 154 publications

(101 citation statements)

References 14 publications

(19 reference statements)

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“…In addition, immunohistochemistry was performed to detect the cell cycle regulatory protein p53, which demonstrated robust positivity in the nuclei of neoplastic lymphocytes in six cases (22.2%), one of which showed focal positivity (data not shown; see Table 1 for summary). These observations are in accord with earlier reports of chromosomal imbalances and low levels of p53 expression in primary CNS lymphomas (7,39) and speculation on the involvement of JCV in "rogue" cells, lymphocytes that exhibit chromosomal damage, perhaps due to nonfunctional p53 (36). Since previous reports have detected the presence of EBV within B-cell lymphomas, we analyzed the samples for EBV by performing immunohistochemistry to detect EBV LMP1 within tumor cells.…”

Section: Resultssupporting

confidence: 88%

Primary Central Nervous System Lymphoma Expressing the Human Neurotropic Polyomavirus, JC Virus, Genome

Valle

Enam

Lara

et al. 2004

J Virol

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Section: Resultssupporting

confidence: 88%

Primary Central Nervous System Lymphoma Expressing the Human Neurotropic Polyomavirus, JC Virus, Genome

Valle

Enam

Lara

et al. 2004

J Virol

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“…In immunocompetent patients, all but 5% of PCNSLs are diffuse large B-cell lymphomas (DLBCLs) [3]. Because they are morphologically indistinguishable from systemic DLBCLs, the World Health Organization classification of tumors of hematopoietic and lymphoid tissues does not recognize PCNSL as a separate entity [4].…”

Section: Pathology and Pathogenesismentioning

confidence: 99%

Primary CNS Lymphoma in Immunocompetent Patients

et al. 2009

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Primary central nervous system lymphoma (PCNSL) constitutes a rare group of extranodal non-Hodgkin's lymphomas (NHLs), primarily of B cell origin, whose incidence has markedly increased in the last three decades. Immunodeficiency is the main risk factor, but the large majority of patients are immunocompetent. Recent evidence suggests a specific tumorigenesis that may explain their particular clinical behavior compared with systemic NHL. The addition of i.v. high-dose methotrexate (MTX) chemotherapy to whole-brain radiotherapy (WBRT) has considerably improved the prognosis, leading to a threefold longer median survival time compared with WBRT alone and represents the current standard of care. However, this combined treatment exposes the patient, especially the elderly, to a high risk for delayed neurotoxicity. In the older population (>60 years), there is growing evidence that MTX-based chemotherapy alone as initial treatment is the best approach to achieve effective tumor control without compromising patient quality of life. In the younger population, the risk for neurotoxicity is much lower, and this strategy is controversial because it may be associated with higher relapse rates. Future efforts should focus on the development of new polychemotherapy regimens allowing the reduction or deferral of WBRT in order to minimize the risk for delayed neurotoxicity. In this setting, intensive chemotherapy with autologous blood stem cell transplantation was recently demonstrated to be feasible and efficient as salvage therapy and is currently being evaluated as part of primary treatment. This review highlights the recent advances in the pathogenesis and treatment of PCNSL in the immunocompetent population.

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“…In contrast, most PCNSLs that occur in immunocompetent patients show a centroblastic polymorphic feature. Epstein-Barr virus (EBV) has been shown to be associated with nearly all AIDSrelated PCNSLs (2, 3), whereas it has been described only rarely in those that occur in immunocompetent patients (4,5). This difference in EBV status in PCNSLs allows us to study morphologic and immunohistochemical features that could be related to EBV.…”

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confidence: 99%

Overexpression of BCL-2, BCL-X, and BAX in Primary Central Nervous System Lymphomas that Occur in Immunosuppressed Patients

et al. 2000

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In contrast to primary central nervous system lymphomas (PCNSLs) that occur in immunocompetent patients, most of those that occur in immunosuppressed patients are associated with Epstein-Barr virus (EBV). BCL-2-related proteins either block or promote cell death, forming homo-or heterodimers with each other. LMP-1, EBV latent protein, has been shown to upregulate BCL-2 and BCL-XL. This observation suggests that these proteins may be involved in the transformation process of EBVinfected cells.Twenty-three cases of PCNSLs were studied: 12 of the patients were immunosuppressed, and 11 were immunocompetent. For all cases, we collected clinical information, histologic data, and immunophenotype and tested for the presence of EBV (EBER-1, LMP-1). Apoptosis was assessed by the TdTmediated dUTP-biotin nick-end labeling method and quantified by image analysis. In three cases, electron microscopy was performed. The BCL-2 family proteins (BCL-2, BCL-X, MCL1, and BAX) and p53 expression were studied by immunohistochemistry on paraffin slides.All cases were classified as diffuse large B-cell lymphomas. PCNSLs in immunosuppressed patients were characterized by EBV association, necrosis, important gliosis, and numerous macrophages. There was no significant difference between the two groups regarding the TdT-mediated dUTP-biotin nick-end labeling staining (P ‫؍‬ .08). In contrast, PCNSLs in immunosuppressed patients were shown to express high levels of BCL-2, BCL-X, and BAX in more than 80% of tumor cells in 7, 10, and 11 cases, respectively. In immunocompetent patients, only one case showed a high level of BCL-2 expression in more than 80% of the cells, whereas BCL-X and BAX were overexpressed in two cases. These differences are significant (P < .05). In contrast, there was no significant difference between the two groups in MCL-1 expression. Besides EBV association and necrosis, PCNSLs related to immunosuppression are characterized by an overexpression of BCL-2-related proteins, without dramatically modifying their susceptibility for apoptosis.

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Primary Central Nervous System Lymphomas in 72 Immunocompetent Patients: Pathologic Findings and Clinical Correlations

Cited by 154 publications

References 14 publications

Primary Central Nervous System Lymphoma Expressing the Human Neurotropic Polyomavirus, JC Virus, Genome

Primary Central Nervous System Lymphoma Expressing the Human Neurotropic Polyomavirus, JC Virus, Genome

Primary CNS Lymphoma in Immunocompetent Patients

Overexpression of BCL-2, BCL-X, and BAX in Primary Central Nervous System Lymphomas that Occur in Immunosuppressed Patients

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