Primary Central Nervous System (CNS) Lymphoma Research Articles

Safety and efficacy of induction immunochemotherapy with rituximab, methotrexate, ifosfamide, and vincristine (R-MIV) in patients with primary CNS lymphoma including recent COVID-19 pandemic experience.

Clinical data on primary central nervous system (CNS) lymphoma (PCNSL) patients is mostly generated from prospective studies, and many frail real-world patients are not included. Recently,the diagnosis and treatment of PCNSL patients was confounded by the COVID-19 pandemic. In particular, treatment with high-dose cytarabine was linked to increased risk of pneumonia and virus persistence. We report on outcome of the induction regimen R-MIV (rituximab, methotrexate, ifosfamide, and vincristine) involving intensive administration of high-dose methotrexate (3.5g/m2 ) with ifosfamide, every 2 weeks and rituximab once per week for six doses. The median age and performance status (PS) for 64 patients was 58 years and 2 (PS 3; 22%) respectively. The overall response rate by magnetic resonance imaging/computed tomography (MRI/CT) was 73% (n=46/63), with an additional 17.5% (n=11/63) patients without measurable disease at baseline. Grade 3-4 haematological toxicity was low for R-MIV (neutropenia: 25% and thrombocytopenia: 1%). Three patients (4.7%) died from treatment-related toxicity. Co-existence of SARS-CoV-2 infection with cytomegalovirus reactivation and the varicella-zoster virus in two patients was fatal. Fifty patients (78%) were eligible for consolidation. Median progression-free and overall survival were not reached (median follow-up: 44 months). In conclusion, the R-MIV regimen is feasible in routine practice, effective and safe, even during the COVID-19 pandemic.

Primary dural lymphoma: a comprehensive literature review and report of a case

Primary dural lymphoma (PDL) is a subtype of primary central nervous system (CNS) lymphoma (PCNSL) with only an extra-axial dural location. It accounts for less than 1% of all CNS lymphomas. PDL is a sporadic CNS tumor, and in the preoperative period, because of imaging characteristics, it is usually mimicking a meningioma. Usually, PDL is a low-grade B-cell lymphoma with a relatively good response to surgical resection with or without radiotherapy. Here we reviewed 102 case reports of PDL in the literature. Then, we present the case of our patient with PDL and explain the complexity of our treatment approach.

ABCL-421 Demographics, Pattern of Care, and Outcomes of Primary CNS Lymphoma-Experience from a Tertiary Care Cancer Center in India

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma with the worst outcomes amongst all extranodal lymphomas. This study analyzed the demographic patterns, risk stratification, treatment regimens used, and outcomes of patients treated at Tata Memorial Center Mumbai, India. This is a retrospective analysis of 142 patients with newly diagnosed primary CNS lymphoma from January 2013 to December 2019. Out of 142 patients, 43 (30.2%) were excluded, and 99 patients were included in the final analysis. Among these 99 patients, 72 (72.7%) were <60 years, 70 (70.7%) had Eastern cooperative oncology group (ECOG) performance status (PS) < 2. Diffuse large B-cell lymphoma (DLBCL) was the most common histology in 86.4% cases and only 1 patient was positive for HIV serology. Multiple intracranial lesions were found in 59.5% and surgical resection was performed in 28.4% of patients. International extranodal lymphoma study group (IELSG) score is available for 63 patients; 34 (54%) high-risk disease. As per Memorial Sloan Kettering Cancer Center (MSKCC) risk grouping, patients were almost equally distributed in all the risk groups. High dose methotrexate (HD-MTX) based regimens were administered to 92 (92.9%) patients, and 72.8% of these patients received rituximab. Of these 92 patients, 59 (64.1 %) patients could complete induction, and 52 patients received consolidation. Majority of patients received high dose cytarabine as consolidation (31 patients) followed by Whole Brain Radiotherapy (19 patients). Thus only 52 patients completed entire course of induction with consolidation therapy. Post completion of consolidation, 49 (94.2 %) patients had a complete response. With a median follow-up duration of 39.2 months, the median progression-free survival (PFS) and the median overall survival (OS) of the patients taken into the analysis (N=99) were 21 and 37 months respectively. On multivariate analysis, age < 60 yrs, ≥5 HD-MTX cycles received & the use of rituximab predicted better OS. Outcomes of patients with PCNSL treated with HD-MTX based therapy are comparable to reported literature however a large proportion of patients do not undergo required treatment despite the curable nature of disease.

Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1/2 clinical trial

AbstractCD19-directed chimerical antigen receptor T-cell (CAR-T) products have gained US Food and Drug Administration approval for systemic large B-cell lymphoma. Because of concerns about potential immune cell-associated neurotoxicity syndrome (ICANS), patients with primary central nervous system (CNS) lymphoma (PCNSL) were excluded from all pivotal CAR-T studies. We conducted a phase 1/2 clinical trial of tisagenlecleucel in a highly refractory patients with PCNSL and significant unmet medical need. Here, we present results of 12 relapsed patients with PCNSL who were treated with tisagenlecleucel and followed for a median time of 12.2 months (range, 3.64-23.5). Grade 1 cytokine release syndrome was observed in 7/12 patients (58.3%), low-grade ICANS in 5/12 (41.6%) patients, and only 1 patient experienced grade 3 ICANS. Seven of 12 patients (58.3%) demonstrated response, including a complete response in 6/12 patients (50%). There were no treatment-related deaths. Three patients had ongoing complete remission at data cutoff. Tisagenlecleucel expanded in the peripheral blood and trafficked to the CNS. Exploratory analysis identified T-cell, CAR T, and macrophage gene signatures in cerebrospinal fluid following infusion when compared with baseline. Overall, tisagenlecleucel was well tolerated and resulted in a sustained remission in 3/7 (42.9%) of initial responders. These data suggest that tisagenlecleucel is safe and effective in this highly refractory patient population. This trial was registered at www.clinicaltrials.gov as #NCT02445248.

Role of targeted therapy in central nervous system lymphoma

Longer life expectancy, better diagnostic measures and advances in neuro-imaging account for the increasing numbers of diagnosed cases of primary central nervous system (CNS) lymphoma (PCNSL). Unfortunately, PCNSL is usually diagnosed late and that leads to poor performance status of patients, reducing their chances of accurate and timely therapy. This accounts for significant differences between real-life treatment outcomes and clinical trials. Although PCNSL had long been considered incurable, rapidly evolving therapeutic paradigms have shown significant progress with an absolute necessity for efficient diagnosis, staging and initiation of therapy conducted at experienced centers. High-dose methotrexate combined with rituximab and high-dose cytarabine in younger patients, or alkylating agents and rituximab in older patients, still remains the standard of care as induction therapy, while relapsed/refractory disease is a challenge necessitating the search for new, safe and effective therapeutic approaches. Thanks to the discovery of the crucial molecular pathways leading to lymphomagenesis, it is now possible to target points of deregulation of specific pathways and stop the cancerous process. The very recent developments of efficient therapies, including high-dose methotrexate-based chemotherapy and targeted therapies comprising the monoclonal antibody rituximab and the immune checkpoint inhibitors lenalidomide and ibrutinib, have brought about improved outcomes. Such novel agents bring hope for better results and seem to hold great promise for the treatment of patients with relapsed/refractory PCNSL. The key to future approaches is to target different molecular pathways in order to overcome mechanisms of resistance.

Innovative Therapeutic Strategies for Primary CNS Lymphoma

Primary central nervous system (CNS) lymphoma (PCNSL) represents 4% of all CNS malignancies and 4–6% of all extranodal lymphomas. Its low incidence is the main reason why it has been difficult to develop guidelines on the treatment and management of PCNSL patients. The lack of consensus around standard therapy and best diagnostic approach, inevitably, affected the outcome of these patients for many years. Current efforts are focusing on: (1) defining the optimal induction and consolidation therapies in fit and frail patients, (2) establishing when and how to use the new non-cytotoxic agents, (3) investigating innovative radiotherapy to mitigate treatment-related neurotoxicity, (4) limiting delays in diagnosis, and (5) improving response assessment with new biological markers and radiological tools. Finally, the complexity of the management of PCNSL patients compels clinicians to provide timely and efficient social, neuropsychological, and physiotherapy support, which is feasible only when there is effective collaboration between the multiple specialists involved in the care of these patients. In the last decade, thanks to multicenter collaborations, important gains have been made, particularly in the front line therapy and in the biological understanding of this disease. The progressive knowledge on molecular profile of PCNSL has justified the recent use of targeted therapy also in these settings of patients. In this review, we discuss important advances in the management of PCNSL and we highlight unresolved questions that should be addressed in the future.

Toxicity of high-dose methotrexate administration at the Sidney Kimmel Cancer Center (SKCC): A retrospective review to guide establishment of an outpatient treatment program.

30 Background: High-dose methotrexate (HDMTX) is administered for the treatment of primary central nervous system (CNS) lymphoma (PCNSL), leptomeningeal metastases, and osteosarcoma, as well as CNS prophylaxis in patients with high-risk lymphoma and leukemia. Treatment is typically administered in an inpatient setting to enable aggressive hydration, urinary alkalinization, and frequent lab monitoring given the risk of acute kidney injury. Multiple pediatric centers have published experiences with outpatient administration of HDMTX. We aim to determine the toxicity rate in adult patients at SKCC receiving HDMTX to identify a population in which to pilot an outpatient HDMTX program. Methods: We performed a retrospective review of all patients receiving inpatient HDMTX at SKCC between January 1, 2018 and October 31, 2019. Results: Seventy-three patients (52% male) with median age of 60 years (range 22-81) received 255 cycles total of HDMTX. Diagnoses include PCNSL/vitreoretinal lymphoma (n=22), diffuse large B-cell lymphoma (n=17), B-cell acute lymphoblastic leukemia (n=16) and other diagnoses (n= 18). Thirty-one cycles were administered as CNS prophylaxis and 224 cycles as treatment, with a median prophylactic dose of 3.5 g/m2 (range 1-3.5) and median treatment dose of 3.5 g/m2 (range 0.25-12). The most common toxicity was acute kidney injury at a median day 3 of the cycle (range 1-7). See the table for details. Conclusions: Acute kidney injury occurred more often in the treatment group compared to prophylaxis group. Of all patients with AKI in the treatment group, 45% had a diagnosis of PCNSL. In the prophylactic group, only 21% of patients (3/14) experienced AKI of which all resolved. Of all AKI events, 90% were Grade 2 and 90% resolved. Based on these results, we plan to pilot an outpatient HDMTX program in patients receiving prophylactic HDMTX to determine its effect on patient quality of life and cost of care. [Table: see text]

The process of somatic hypermutation increases polyreactivity for central nervous system antigens in primary central nervous system lymphoma.

The immunoglobulin (Ig) heavy and light chain variable gene mutational pattern of the B-cell receptor (BCR) in primary central nervous system lymphoma (PCNSL) cells suggests antigenic selection to drive pathogenesis and confinement to the central nervous system (CNS). This hypothesis is supported by the observation that the tumor B-cell receptor (tBCR) of PCNSL is polyreactive and may be stimulated by CNS proteins. To obtain further insight into the role of the germinal center (GC) reaction on BCR reactivity, we constructed recombinant antibodies (recAb) with Ig heavy and light chain sequences of the corresponding naïve BCR (nBCR) by reverting tBCR somatic mutations in ten PCNSL. Analysis of nBCR-derived recAb reactivity by a protein microarray and immunoprecipitation demonstrated auto- and polyreactivity in all cases. Self- /polyreactivity was not lost during the GC reaction; surprisingly, tBCR significantly increased self-/polyreactivity. In addition to proteins recognized by both the nBCR and tBCR, tBCR gained self-/polyreactivity particularly for proteins expressed in the CNS including proteins of oligodendrocytes/ myelin, the S100 protein family, and splicing factors. Thus, in PCNSL pathogenesis, a faulty GC reaction may increase self-/polyreactivity, hereby facilitating BCR signaling via multiple CNS antigens, and may ultimately foster tumor cell survival in the CNS.

Primary central nervous system lymphoma: advances in treatment strategies

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare subtype of aggressive non-Hodgkin lymphoma originating within the CNS. Whole brain irradiation (WBRT) has been utilized in combination with high-dose methotrexate (HD-MTX), unfortunately with a high rate of late neurocognitive decline, particularly in the elderly. HD-MTX-based combination chemotherapy regimens have been developed as induction therapy for PCNSL and shown to improve response rates. Consolidation treatment, such as reduced-dose WBRT or high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HDT-ASCT) is vital to controlling the disease. Two phase II trials randomizing PCNSL patients to WBRT or HDT-ASCT were recently published, showing comparable survival but better neurocognitive function in patients receiving HDT-ASCT. A key agent in HDT-ASCT for PCNSL is thiotepa, which, however, has been unavailable in Japan since 2011. Therefore, a clinical trial of HDT-ASCT with thiotepa was performed, and we are currently awaiting drug approval. Several targeted drugs are being trialed in patients with relapsed or refractory PCNSL. The treatment strategy of PCNSL is still developing to improve survival and reduce toxicity.

Utility of flouro-deoxy-glucose positron emission tomography/computed tomography in the diagnostic and staging evaluation of patients with primary CNS lymphoma.

Aim:To prospectively assess the clinical utility of pretreatment flouro-deoxy-glucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients with primary central nervous system (CNS) lymphoma (PCNSL).Materials & methods:Patients with suspected/proven PCNSL underwent baseline whole-body 18F-FDG-PET/CT. Maximum standardized uptake value and tumor/normal tissue ratios were compared between CNS lymphoma and other histological diagnoses.Results:The mean maximum standardized uptake value (27.5 vs 18.2; p = 0.001) and mean tumor/normal tissue ratio (2.34 vs 1.53; p < 0.001) of CNS lymphoma was significantly higher than other histologic diagnoses. Five of 50 (10%) patients with biopsy-proven CNS lymphomas had pathologically increased FDG-uptake at extraneuraxial sites uncovering systemic lymphoma.Conclusion:Pretreatment whole-body 18F-FDG-PET/CT provides valuable complementary information in the diagnostic and staging evaluation of patients with PCNSL to guide therapeutic decision-making.

The Impact of Early Corticosteroid Pretreatment Before Initiation of Chemotherapy in Patients With Primary Central Nervous System Lymphoma.

The optimal timing of corticosteroid (CS) treatment in patients with primary central nervous system (CNS) lymphoma (PCNSL) remains controversial. While poor clinical presentation may justify early treatment with CS, this may ultimately result in reduced concentrations of chemotherapeutic agents via perturbations in the permeability of the blood-brain barrier. To investigate whether early CS exposure is associated with beneficial outcomes and/or reduced occurrence of adverse events as opposed to delayed/concomitant administration. Herein we performed a retrospective observational analysis using patients that were prospectively entered into a database. All patients whom were admitted to the University Hospital between 2009 and 2015 with newly diagnosed PCNSL were included within our study. Our cohort included 50 consecutive patients diagnosed with PCNSL; of these, in 30 patients CS administration was initiated prior to chemotherapy (early), whilst in the remaining 20 patients CS administration was initiated concomitantly with their chemotherapeutic regimen (concomitant). Within the early vs concomitant CS administration groups, no significant differences were observed with regard to progression-free survival (PFS) (P=.81), overall survival (OS) (P=.75), or remission (P=.68; odds ratio 0.76 and confidence interval [95%] 0.22-2.71). Critically, the timing of CS initiation was not associated with either PFS (P=.81) or PFS (P=.75). Early CS administration was not associated with a deterioration in response to chemotherapy, PFS, or OS. As such, administration of CS prior to initiation of chemotherapy is both reasonable and safe for patients with newly diagnosed PCNSL.

Evolving Treatments for Primary Central Nervous System Lymphoma.

Primary central nervous system (CNS) lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma that remains confined to the CNS neuroaxis during its natural history of disease and is therefore considered stage IE disease. PCNSL is diffuse large B-cell lymphoma (DLBCL) morphology in more than 95% of patients and is designated primary diffuse large B-cell lymphoma of the CNS on the basis of the 2017 World Health Organization classification of hematopoietic and lymphoid tumors. Rapidly evolving therapeutic paradigms have been linked to evidence of progress in PCNSL, a disease long considered to be incurable. Increasing evidence supports the need for efficient diagnosis, staging, and initiation of therapy, ideally at centers with experience with this type of brain cancer. High-dose methotrexate (MTX) remains a cornerstone of induction regimens, and most data support the use of rituximab. However, clinical research challenges must address key questions, including the development of ever more effective and less toxic induction regimens and the selection of the most appropriate and effective consolidation approaches, as well as the fact that, increasingly, PCNSL affects older patients who do not tolerate strong genotoxic irradiation or high-dose chemotherapy (HDC)-based strategies. Maintenance therapy, immunotherapy, and the implementation of targeted agents on the basis of the molecular and biologic properties of the disease create opportunities for precision medicine and the potential for long-term disease-free survival and cure, with minimal treatment-related neurotoxicity, for a greater fraction of patients.

Neuroradiological features of lymphomatosis cerebri: A systematic review of the English literature with a new case report.

Lymphomatosis cerebri is a rare form of diffusely infiltrating primary central nervous system (CNS) lymphoma (PCNSL). The neuroradiological findings of lymphomatosis cerebri have not been adequately characterized, as the relevant literature consists only of case reports and small case series. The present study describes an unusual presentation of lymphomatosis cerebri in a 56-year-old immunocompetent woman who presented with diffusely infiltrating lesions with perivascular curvilinear enhancement on initial magnetic resonance imaging (MRI) and multiple nodules on the later follow-up computed tomography (CT) scan. A systematic review of the literature is also performed searching PubMed between January 1996 and December 2016 to collect all pertinent case reports and series written in the English language with pathologically confirmed lymphomatosis cerebri and diffuse infiltrative PCNSL without cohesive masses on initial MRI. A total of 45 cases were identified from 39 articles and the present case report. The patient ages ranged from 28 to 85 years (mean, 57.3 years). Only 3 patients (6.7%) were immunosuppressed (acquired immune deficiency syndrome patients). The most common clinical presentation was cognitive changes or dementia (46.7%). Cerebrospinal fluid analysis in all cases was non-specific. Diffuse and asymmetric abnormal T2-hyperintensity in deep and subcortical white matter was observed in all cases. Gray matter involvement (17.8%), spreading along the corticospinal tract (35.6%) and a slight mass effect (51.1%) also were observed. Contrast-enhanced patterns on MRI could be divided into three forms of non-enhancement (64.4%) and non-mass-like enhancement (35.6%) on initial MRI, as well as nodular or mass-like enhancement on the later follow-up MRI (15.6%). There were non-specific findings on magnetic resonance spectroscopy for 4 patients, on positron emission tomography/CT for 12 patients and on single-photon emission CT for 1 patient. Diagnosis was established by brain biopsy in 35 cases (77.8%) and autopsy in 9 cases (20%), involving B-cell lymphoma in 40 cases (88.9%) and T-cell lymphoma in 4 cases (8.9%). In conclusion, lymphomatosis cerebri, namely diffuse PCNSL or diffuse lymphoma of the CNS, is characterized by rapidly progressive dementia in the elderly, diffusely infiltrated CNS white matter along the corticospinal tract, possible involvement of the gray matter, a slight mass effect and varied contrast-enhancement patterns on MRI. Non-enhancement or non-mass-like enhancement on MRI may be a special form of diffuse PCNL during disease development and progression.

Absence of Lymphatic Vessels in PCNSL May Contribute to Confinement of Tumor Cells to the Central Nervous System.

Primary central nervous system (CNS) lymphoma (PCNSL) is a mature lymphoma of the diffuse large B-cell lymphoma (DLBCL) type confined to the CNS. Despite cytomorphological similarities between PCNSL and systemic DLBCL, molecular differences between both entities have been identified. The exclusively topographical restriction of PCNSL to the CNS is an unexplained mystery. To address the question of whether the unique lymphatic drainage system of the CNS, which differs from that of other organs, may play a role for this peculiar behavior, we investigated a series of 20 PCNSLs for the presence of lymphatic vessels by immunohistochemistry for Lyve-1, podoplanin, and Prox-1 expression. All PCNSLs lacked lymphatic vessels and, in this regard, were similar to 20 glioblastoma multiforme samples. In contrast to these tumors, all of which were located in the deep brain parenchyma, dural and meningeal DLBCL harbored lymphatic vessels that expressed Lyve-1 (3/8 tumors), podoplanin (5/8 tumors), and Prox-1 (5/8 tumors) in areas where the tumors had invaded the fibrous tissue of the dura. These data indicate that local topographical characteristics of the specific lymphatic drainage system may contribute to confinement of the tumor cells in PCNSL and malignant gliomas.

Beyond high-dose methotrexate and brain radiotherapy: novel targets and agents for primary CNS lymphoma

While there has been significant progress in outcomes for patients diagnosed with primary central nervous system (CNS) lymphoma (PCNSL), survival rates will likely plateau with the current armamentarium of agents used to treat these patients. Moreover, given that PCNSL increasingly impacts an older population, a significant proportion of patients are not eligible for intensive therapies such as high-dose chemotherapy or whole-brain radiation. There is a need for the development of novel agents, which target key survival pathways in order to continue to make progress in this disease. We reviewed the key molecular pathways and genomic aberrations in PCNSL in order to identify candidate targets. We focused on molecules and pathways that have been identified and confirmed by more than one investigator or methodology. While PCNSL tumors usually express a BCL6+, MUM1+ 'activated, germinal center' immunophenotype, they exhibit multiple shared genetic properties with ABC-type diffuse large B-cell lymphomas. Candidate targets and pathways include NFkB, the B-cell receptor, the JAK/STAT pathway, IRF4, BCL-6 as well as PIM kinases. Elements of the tumor microenvironment that may be exploited therapeutically include chemokine pathways, as well as macrophage and T-cell responses. There is a significant need for developing novel therapies in PCNSL, given that an increasing proportion of patients are not eligible for high-dose chemotherapy and brain radiation is associated with detrimental cognitive side-effects. We provide an overview of potential drug targets and novel agents that may be integrated with existing strategies in order to make further progress in this disease.

Primary CNS lymphoma other than DLBCL: a descriptive analysis of clinical features and treatment outcomes

Diffuse large B-cell lymphoma (DLBCL) constitutes most primary central nervous system (CNS) lymphoma (PCNSL), whereas T-cell, low-grade and Burkitt’s lymphomas (BL) are rarely encountered. Due to the paucity of cases, little is known about the clinical features and treatment outcomes of PCNSL other than DLBCL. The objective of this study was to describe the clinical characteristics and outcomes for patients with PCNSL other than DLBCL. Fifteen patients, newly diagnosed with PCNSLs other than DLBCL between 2000 and 2010, were included. The male to female ratio was 0.67:1 with a median age of diagnosis of 31 years (range 18–59). Pathologic distributions were as follows: peripheral T-cell lymphoma (PTCL; n = 7), marginal zone B-cell lymphoma (MZBCL; n = 1), lymphoplasmacytic lymphoma (LPL; n = 2), Burkitt’s lymphoma (n = 1), other unspecified (T-cell lineage, n = 2; B-cell lineage, n = 2). Thirteen patients (87%) showed Eastern Cooperative Oncology Group performance score (ECOG PS) 1–2. The remaining two were one PTCL patient and one Burkitt’s lymphoma patient. Of the nine patients with T-cell lymphoma, five (56%) had multifocal lesions, and one (20%) with LPL of the five patients with B-cell lymphoma showed a single lesion. Leptomeningeal lymphomatosis was identified in two patients (one with Burkitt’s lymphoma and one with unspecified B-cell lymphoma). Two patients (22%) with T-cell lymphoma died 7.7 and 23.3 months later, respectively, due to disease progression, despite HD-MTX-based therapy. Six patients with T-cell lymphoma (6/9, 66.7%) and four patients with low-grade B-cell lymphoma (4/5, 80%) achieved complete response and have survived without relapse (Table 3). One patient with Burkitt’s lymphoma showed poor clinical features with ECOG PS 3, deep structure, multifocal, and leptomeningeal lymphomatosis, and died 7.6 months after the initiation of treatment. In comparison with previously reported DLBCLs (median OS 6.4 years, 95% CI 3.7–9.1 years), T-cell lymphoma showed equivocal or favorable clinical outcomes and low-grade B-cell lymphomas, such as MZBCL and LPL, had a good prognosis. However, primary CNS Burkitt’s lymphoma presented poor clinical outcomes and showed a comparatively aggressive clinical course. In conclusion, primary CNS lymphoma other than DLBCL occurred more in younger patients and showed a generally good prognosis, except for Burkitt’s lymphoma. Further research on treatment strategies for Burkitt’s lymphoma is needed.

Imaging in Primary Central Nervous System Lymphoma

Primary central nervous system (CNS) lymphoma (PCNSL) accounts for approximately 3% of all primary CNS tumors. Congenital or acquired immunodeficiency is the only established risk factor for PCNSL. Rates decreased slightly in the mid-1990s, concordantly with the decreasing rates of AIDS. However, the incidence has been increasing in the elderly immunocompetent population, and this trend seems to be independent of improvements in diagnostic techniques, and of overall trends in the incidence of brain tumors and systemic lymphomas. This study presents our experience with the imaging features of PCNSL. Computed tomography (CT) and magnetic resonance imaging (MRI) findings were reviewed in a series of 38 cases of pathologically proven PCNSL. The incidence rate of PCNSL was higher in men than in women (58% versus 42%). Mean age at presentation was 63 years; 120 lesions were demonstrated in the 38 patients, with a 53% frequency of tumor multiplicity. Both CT and MR mainly showed solitary or multiple well-defined round or oval-shaped mass lesions, typically hyperdense on unenhanced CT scans, iso to hypointense on T2 MR weighted images. These lesions also showed an increased signal intensity on diffusion-weighted images. Virtually all lesions enhanced after intravenous administration of contrastmedium. On (1)H-magnetic resonance spectroscopy ((1)H-MRS) most lesions presented increased Cho/Cr, Cho/NAA and lactate/Cr ratios when compared to normal gray matter. No changes in the imaging presentation have occurred over the past two decades, apart from lesions now being smaller at diagnosis. Our imaging findings are in agreement with the existing literature data and with the reported increasing trend of multifocal tumors. Our epidemiologic results add value to the existing evidence of increasing incidence rates among the immunocompetent elderly population.

Primary Central Nervous System Lymphoma

Primary central nervous system (CNS) lymphoma (PCNSL), an uncommon variant of extranodal non-Hodgkin lymphoma (NHL), can affect any part of the neuraxis including the eyes, brain, leptomeninges, or spinal cord. It accounts for approximately 3% of all the primary CNS tumors diagnosed each year in the United States. Congenital or acquired immunodeficiency is the only established risk factor for PCNSL, and individuals with human immunodeficiency virus (HIV) infection are at greater risk for developing this tumor. Infection with HIV likely accounted for the increased incidence in PCNSL observed from 1970 to 2000, but over the last decade the number of cases of PCNSL has stabilized or decreased to about 0.47 cases per 100 000 persons. Owing to the rarity of PCNSL, the disease has been challenging to study and an effective standard of care has been difficult to establish. Unfortunately, although durable remissions may be achieved for some patients with PCNSL, the tumor relapses in most cases. In this review, we will focus on PCNSL in the immunocompetent host.

Extra-axial Primary Intracranial Cerebral Lymphoma Mimicking Meningioma

Primary central nervous system (CNS) lymphoma (PCNSL) is a nervous system-seeking extranodal non-Hodgkin lymphoma. It represents 3.1% of all primary brain tumors and 2% to 3% of non-Hodgkin lymphomas. It can be difficult to distinguish primary CNS lymphoma from other brain tumors on initial radiographic images. Primary CNS lymphomas have a different appearance on computed tomography scan or magnetic resonance imaging. We present a patient in whom difficulty was encountered in the establishment of a (primary CNS lymphoma compared with meningioma) using conventional diagnostic approaches. The clinical, radiologic features, and the treatment are described and discussed together with a review of literature and previous reports.

Primary central nervous system lymphoma: A profile of 26 cases from western India

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare malignant non-Hodgkin's lymphoma and it accounts for 1% of all intracranial tumors. Only a few PCNSL studies have been reported from India, and studies on prognostic factors determining outcome, or evaluation of the response to currently accepted treatment, are lacking. This study attempts to further delineate the clinical, radiological and pathological profile of PCNSL in India, to evaluate response to treatment and to assess usefulness of the International Extranodal Lymphoma Study Group (IELSG) score. All patients with pathologically proven PCNSL admitted over three years at a large tertiary care institution were studied. Clinical features, IELSG prognostic score, imaging and pathological features, and response to treatment were evaluated. Results were analyzed using chi 2 test. Of 26 patients found, all except two were immunocompetent. Median age at diagnosis was 59 years. Focal deficits (76.9%) and neuropsychiatric symptoms (57.6%) were the commonest presenting complaints. Except for one case, at least some contrast enhancement was seen in brain lesions of all patients. Pathological studies showed high grade diffuse large B-cell (DLBCL) histology in 96.2% of patients. Of 22 patients who received methotrexate (MTX) based chemotherapy with/without radiotherapy; six died, with a response rate of 72.7%. Median survival was 10 months. Median follow-up duration was 14.5 months. Four patients developed treatment-related cognitive decline. All six patients with IELSG score of 4/5 died, while all 16 patients with a score of 0-3 survived. PCNSL presents most commonly in the sixth decade with focal neurological deficit, behavioral symptoms and cognitive decline. High grade DLBCL is the commonest histological subtype. Steroids should ideally be withheld until biopsy as they may confound the diagnosis. Most immunocompetent patients respond well to high dose MTX-based chemotherapy with/without radiation. High IELSG scores correlate with worse prognosis in patients with PCNSL.