Primary central nervous system lymphoma.
01 Nov 2008-Archives of Pathology & Laboratory Medicine (Arch Pathol Lab Med)-Vol. 132, Iss: 11, pp 1830-1834
TL;DR: The differential diagnosis of PCNSL includes central nervous system gliomas, metastatic tumors, demyelinating disorders, subacute infarcts, and space-occupied lesions due to an infectious etiology.
Abstract: Primary central nervous system lymphoma (PCNSL) is an uncommon extranodal non-Hodgkin lymphoma. Its incidence has increased during the last 3 decades and has been reported in both immunocompromised and immunocompetent patients. Immunocompromised patients are affected at a younger age compared with immunocompetent patients. It presents with raised intracranial pressure and focal neurologic and neuropsychiatric symptoms. The lesions are typically solitary. The majority of the lesions are located in the periventricular area, whereas in a few cases they are located in the supratentorial area. Diffuse large B-cell lymphomas constitute most PCNSLs, whereas T-cell, low-grade, anaplastic, and Hodgkin lymphomas are rarely encountered. The morphology of PCNSL shows a characteristic angiocentric pattern and is positive for B-cell markers by immunohistochemistry. The differential diagnosis of PCNSL includes central nervous system gliomas, metastatic tumors, demyelinating disorders, subacute infarcts, and space-occupying lesions due to an infectious etiology. The understanding of the molecular mechanisms involved in the pathogenesis of PCNSL and the identification of molecular biomarkers have lagged behind that of systemic nodal lymphomas. Primary central nervous system lymphomas are treated with combined radiotherapies and chemotherapies. The prognosis for PCNSL is worse than for other extranodal lymphomas.
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TL;DR: There is an increase in incidence of PCNSL in the elderly, and elderly blacks have lower incidence compared with white population, and survival remains poor and is negatively dominated by factors associated with HIV infection and advanced age.
Abstract: Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal non-Hodgkin lymphoma that accounts for ∼4% of newly diagnosed central nervous system (CNS) tumours. The objective of this study was to analyse the epidemiology, incidence, and outcome of these rare tumours. Primary brain and CNS lymphoma cases were identified from the Surveillance, Epidemiology, and End Results (SEER) research data sets for the years 1980–2008 for analysis of trends in incidence and survival. SEER*Stat v. 7.0.4 software was used to analyse the data. The overall incidence rate of PCNSL was 0.47 per 100 000 person-years. The incidence was significantly higher in males compared with females, blacks aged 0–49 years at diagnosis compared with whites, and whites aged 50 years and older at diagnosis compared with blacks. After a significant decline in incidence between 1995 and 1999, incidence rates rose slightly; those aged 75+ years at diagnosis had the most dramatic increase in incidence rates over time. Five-year survival rates were significantly higher in whites compared with blacks aged 0–49 years at diagnosis, but was primarily driven by white women aged 0–49 years. There is an increase in incidence of PCNSL in the elderly, and elderly blacks have lower incidence compared with white population. Survival remains poor and is negatively dominated by factors associated with HIV infection and advanced age.
400 citations
Cites background or result from "Primary central nervous system lymp..."
...Consistent with other series, our analysis of overall survival reveals that PCNSL is associated with poor long-term outcomes (Fine and Mayer, 1993; Pulido et al, 2009; Norden et al, 2011)....
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...Depending on the period of analysis during the HIV/AIDS epidemic and therapeutic history investigators have described both an increase and decrease in incidence of PCNSL (Fine and Mayer, 1993; Kadan-Lottick et al, 2002; Olson et al, 2002; Hoffman et al, 2006)....
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TL;DR: New CT and MR imaging techniques and metabolic imaging have demonstrated characteristic findings in CNS lymphoma, aiding in its differentiation from other CNS lesions, and advanced imaging techniques may, in the future, substantially improve the diagnostic accuracy of imaging, ultimately facilitating a noninvasive method of diagnosis.
Abstract: CNS lymphoma consists of 2 major subtypes: secondary CNS involvement by systemic lymphoma and PCNSL. Contrast-enhanced MR imaging is the method of choice for detecting CNS lymphoma. In leptomeningeal CNS lymphoma, representing two-thirds of secondary CNS lymphomas, imaging typically shows leptomeningeal, subependymal, dural, or cranial nerve enhancement. Single or multiple periventricular and/or superficial contrast-enhancing lesions are characteristic of parenchymal CNS lymphoma, representing one-third of secondary CNS lymphomas and almost 100% of PCNSLs. New CT and MR imaging techniques and metabolic imaging have demonstrated characteristic findings in CNS lymphoma, aiding in its differentiation from other CNS lesions. Advanced imaging techniques may, in the future, substantially improve the diagnostic accuracy of imaging, ultimately facilitating a noninvasive method of diagnosis. Furthermore, these imaging techniques may play a pivotal role in planning targeted therapies, prognostication, and monitoring treatment response.
365 citations
Cites background from "Primary central nervous system lymp..."
...enhancement is reported in up to 75% of cases.(28,31,39)...
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...Immunodeficient patients with PCNSL are often diagnosed with multifocal lesions, which are reported in 30%– 80% of patients with AIDS-related PCNSL (Fig 5).(28,31,39)...
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...Multiple lesions are reported in 20%– 40% of non-AIDS PCNSLs,(14,15,27,29,31) and ringlike enhancement, in 0%–13% (Figs 2 and 3).(14,29,31,32) Linear enhancement along perivascular spaces is highly suggestive of PCNSL....
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TL;DR: These new findings offer a plausible explanation for the notorious persistence and stability of cerebrospinal fluid oligoclonal bands and outline the possibly double‐edged effects of B cells and immunoglobulin in the CNS.
Abstract: B cells have long played an enigmatic role in the scenario of multiple sclerosis pathogenesis. This review summarizes recent progress in our understanding of B-cell trafficking, survival, and differentiation in the central nervous system (CNS). We propose four possible routes of intrathecal immunoglobulin-producing cells. The inflammatory CNS provides a unique, B-cell-friendly environment, in which B lineage cells, notably long-lived plasma cells, can survive for many years, perhaps even for a lifetime. These new findings offer a plausible explanation for the notorious persistence and stability of cerebrospinal fluid oligoclonal bands. Furthermore, we highlight similarities and differences of intrathecal immunoglobulin production in multiple sclerosis patients and patients with other CNS inflammatory conditions. Finally, we outline the possibly double-edged effects of B cells and immunoglobulin in the CNS and discuss various therapeutic strategies for targeting the B-cell response.
275 citations
Cites background from "Primary central nervous system lymp..."
...pathogenesis of primary CNS lymphomas, which are almost exclusively of B-cell origin.(42) These lymphomas...
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TL;DR: Current knowledge about EMV functions in the nervous system under both physiological and pathological conditions, as well as emerging EMV-based therapies that could be applied to the nervousSystem in the foreseeable future are summarized.
Abstract: Extracellular membrane vesicles (EMVs) are nanometer sized vesicles, including exosomes and microvesicles capable of transferring DNAs, mRNAs, microRNAs, non-coding RNAs, proteins, and lipids among cells without direct cell-to-cell contact, thereby representing a novel form of intercellular communication. Many cells in the nervous system have been shown to release EMVs, implicating their active roles in development, function, and pathologies of this system. While substantial progress has been made in understanding the biogenesis, biophysical properties, and involvement of EMVs in diseases, relatively less information is known about their biological function in the normal nervous system. In addition, since EMVs are endogenous vehicles with low immunogenicity, they have also been actively investigated for the delivery of therapeutic genes/molecules in treatment of cancer and neurological diseases. The present review summarizes current knowledge about EMV functions in the nervous system under both physiological and pathological conditions, as well as emerging EMV-based therapies that could be applied to the nervous system in the foreseeable future.
259 citations
Cites background from "Primary central nervous system lymp..."
...These three viruses are – herpes simplex virus type 1 (HSV-1), which in immune compromised patients can cause viral encephalitis (Steiner, 2011); the tumorigenic herpes virus, Epstein–Barr virus (EBV), which can cause central nervous system (CNS) lymphomas (Gerstner and Batchelor, 2010); and human immunodeficiency virus (HIV), which can lead to neurocognitive deficits, dementia, and premature brain aging (Gannon et al....
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TL;DR: The aim of this monograph is to provide a chronology of key events and milestones in the development of HIV/AIDS-related cancers over a 12-month period from 1989 to 2002, and to promote awareness of the importance of timely diagnosis and ART.
Abstract: M Bower, S Collins, C Cottrill, K Cwynarski, S Montoto, M Nelson, N Nwokolo, T Powles, J Stebbing, N Wales and A Webb, on behalf of the AIDS Malignancy Subcommittee Department of Oncology, Chelsea & Westminster Hospital, London, UK, HIV i-Base and UK-CAB, London, UK, St Bartholomew’s Hospital, London, UK, Royal Free Hospital, London, UK, Hammersmith Hospital, London, UK and Royal Sussex County Hospital, Brighton, UK
216 citations
References
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Book•
01 Jan 2000
TL;DR: Tumours of the haemopoietic system Malignant lymphomas Histiocytic tumours, Familial tumour syndromes, and metastatic tumours ofThe CNS.
Abstract: 1: Astrocytic tumours Diffuse astrocytomas Low-grade diffuse astrocytomas Anaplastic astrocytoma Glioblastoma Giant cell glioblastoma Gliosarcoma Pilocytic astrocytoma Pleomorphic xanthoastrocytoma 2: Oligodendroglial tumours and mixed gliomas Oligodendroglioma Anaplastic oligodendroglioma Mixed gliomas Oligoastrocytoma Anaplastic oligoastrocytoma Other mixed gliomas 3: Ependymal tumours Ependymoma and variants Anaplastic ependymoma Myxopapillary ependymoma 4: Choroid plexus tumours 5: Neuroepithelial tumours of uncertain origin Astroblastoma Polar spongioblastoma Gliomatosis cerebri 6: Neuronal and mixed neuronal-glial tumours Gangliocytoma and ganglioglioma Desmoplastic infantile astrocytoma and ganglioglioma Dysembryoplastic neuroepithelial tumours Paraganglioma 7: Pineal parenchymal tumours Pineoblastoma Pineocytoma Mixed pineoblastoma/pineocytoma 8: Embryonal tumours Medulloepithelioma Central neuroblastoma and ganglioneuroblastoma Ependymoblastoma Medulloblastoma Medullomyoblastoma Melanotic medulloblastoma Lipomatous medulloblastoma Supratentorial PNET Atypical teratoid/rhabdoid tumour 9: Peripheral neuroblastic tumours Olfactory neuroblastoma Neuroblastic tumours of the adrenal gland and sympathetic nervous system 10: Tumours of cranial and peripheral nerves Schwannoma Neurofibroma Malignant peripheral nerve sheath tumour (MPNST) 11: Meningeal tumours Meningiomas Mesenchymal, non-meningothelial tumours Haemangiopericytoma Melanocytic lesions 12: Tumours of the haemopoietic system Malignant lymphomas Histiocytic tumours 13: Germ cell tumours 14: Familial tumour syndromes Neurofibromatosis type 1 Neurofibromatosis type 2 Von Hippel-Lindau disease and capillary haemangioblastoma Tuberous sclerosis complex and subependymal giant cell astrocytoma TP53 germline mutations and the Li-Fraumeni syndrome Cowden syndrome Turcot syndrome Naevoid basal cell carcinoma syndrome 15: Tumours of the sellar region Craniopharyngioma 16: Metastatic tumours of the CNS.
1,651 citations
TL;DR: Dysregulation of STAT-responsive genes may underlie the inflammatory disease in BCL-6-deficient mice and participate in lymphoid malignancies.
Abstract: The gene encoding the BCL-6 transcriptional repressor is frequently translocated and mutated in diffuse large cell lymphoma. Mice with a disrupted BCL-6 gene developed myocarditis and pulmonary vasculitis, had no germinal centers, and had increased expression of T helper cell type 2 cytokines. The BCL-6 DNA recognition motif resembled sites bound by the STAT (signal transducers and activators of transcription) transcription factors, which mediate cytokine signaling. BCL-6 could repress interleukin-4 (IL-4)-induced transcription when bound to a site recognized by the IL-4-responsive transcription factor Stat6. Thus, dysregulation of STAT-responsive genes may underlie the inflammatory disease in BCL-6-deficient mice and participate in lymphoid malignancies.
920 citations
TL;DR: The new edition of this publication opens with the recently revised WHO Classification of Tumors of the Nervous System and then systematically presents each of these tumors and familial tumor syndromes in a …
Abstract: Pathology and Genetics of Tumours of the Nervous System. Paul Kleihues, Webster K. Cavenee, eds. IARC, Lyon, France. 2000, 314 pp.
The new edition of this publication opens with the recently revised WHO Classification of Tumors of the Nervous System (Working Group, 1999) and then systematically presents each of these tumors and familial tumor syndromes in a …
683 citations
"Primary central nervous system lymp..." refers background in this paper
...Primary CNS lymphoma may present either as an isolated lesion or as a combination of the following features: (1) discrete or diffuse intracranial lesions that are either solitary or multiple, (2) ocular lymphomas with or without other lesions, and (3) leptomeningeal surface and spinal cord lesions....
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...The majority (60%–85%) of ALCLs show t(2;5) that fuses ALK (anaplastic large cell kinase) on chromosome 2, with the nucleophosmin on chromosome 5....
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TL;DR: An international group of experts meeting to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow to develop better therapies for patients.
Abstract: Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.
673 citations
"Primary central nervous system lymp..." refers background in this paper
...Primary CNS lymphoma may present either as an isolated lesion or as a combination of the following features: (1) discrete or diffuse intracranial lesions that are either solitary or multiple, (2) ocular lymphomas with or without other lesions, and (3) leptomeningeal surface and spinal cord lesions....
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TL;DR: Paul Kleihues and Webster Cavenee, eds, pp 314, IARC Press, Lyon 2000.
Abstract: Paul Kleihues and Webster Cavenee, eds, pp 314, IARC Press, Lyon 2000. Price £46.00. ISBN 92 832 24094
533 citations