Primary CNS Lymphoma in Immunocompetent Patients

Abstract

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.

The diagnostic role and dynamic changes in cerebrospinal fluid neopterin during treatment of patients with primary central nervous system lymphoma

“…MRI does not have a high specificity for distinguishing PCNSL from glioma and metastatic brain tumors39, 40 and often results in misdiagnosis 6, 8, 9. In the present study, the sensitivity of MRI for the diagnosis of PCNSL was 52.4% (11/21), whereas the sensitivity of CSF Npt concentration for the diagnosis of PCNSL was 90% (9/10) in the 10 false‐negative PCNSL cases.…”

“…PCNSL is commonly associated with a poor prognosis. High‐dose methotrexate‐based chemotherapy (H‐MTX) has greatly improved the prognosis of PCNSL patients as compared to that with whole‐brain radiotherapy (WBRT) 5, 6. High‐dose chemotherapy followed by autologous stem cell transplantation as the first‐line treatment has been shown to improve 2‐year survival in elderly patients with PCNSL 7…”

“…Magnetic resonance imaging (MRI), especially contrast‐enhanced MRI, is the method of choice for the detection of PCNSL. However, as PCNSL does not have a characteristic radiological feature, misdiagnosis is not uncommon,6, 8, 9 and the differential diagnosis of PCNSL from other brain tumors such as meningioma, glioma, and metastatic brain tumors and some inflammatory diseases such as sarcoidosis and multiple sclerosis is typically challenging 8. Indeed, correct diagnosis of an atypical focal brain lesion based solely on radiological examination is a formidable challenge.…”

“…In addition, diagnosis based on brain biopsy specimens obtained after craniotomy or stereotactic brain biopsy can result in a failure rate of approximately 10%‐35% in patients with rapidly deteriorating neurological conditions 10. Cytology or tumor biomarkers in the cerebrospinal fluid (CSF) are important for diagnosis and differential diagnosis of PCNSL, especially for patients who are not suitable for brain biopsy 6, 11. Identification of diagnostic biomarkers may help in the early diagnosis and treatment of PCNSL and improve patient prognosis.…”

Findings at presentation in primary CNS diffuse large B-cell lymphoma of the brain: A comparison of immunocompetent and immunodeficient patients

“…The incidence of PCNSL in Western countries is five per one million person-years [3] . After a continual increase over the past two decades, epidemiologic data suggest a recent stabilization or decrease in the incidence of PCNSL [1] , particularly among young patients suffering from AIDS, probably associated with the development of new active antiviral drugs.…”