Clinicopathological analysis of primary central nervous system lymphoma in patients with or without HIV infection.

The clinicopathological features of HIV-related primary central nervous system lymphoma (PCNSL) and immunocompetent primary central nervous system lymphoma (IC-PCNSL) were found to be distinct. Thirty-seven patients with HIV-related PCNSL and thirty patients with IC-PCNSL were included in our study. Hematoxylin & eosin (HE) staining, immunohistochemical detection using CD10, MUM1, CD20, Bcl-2, Bcl-6, p53, C-MYC, Ki67, methyltransferase like factor 3 (METTL3) antibodies and Epstein-Barr encoding region (EBER) in situ hybridization were performed. All of the patients were classified as the diffuse large B-cell lymphoma (DLBCL) histological type. Patients with HIV-related PCNSL were younger and more likely to be male, with elevated lactate dehydrogenase (LDH) and low sugar content in cerebrospinal fluid (CSF) compared to patients with IC-PCNSL.The positive rates of METTL3, Bcl-2, p53 and EBER were significantly higher in HIV-related PCNSL patients than in IC-PCNSL patients. Furthermore, we also found that the expression of METTL3 was lower in germinal centre B-cell (GCB)-like DLBCL (n = 7) than in non-GCB like DLBCL (n = 30) in HIV-related PCNSL (P = 0.030); however, in IC-PCNSL patients, the expression of METTL3 was not significantly different between GCB-like DLBCL and non-GCB-like DLBCL (P = 0.670). Although the manifestations are similar in PCNSL patients with and without HIV, HIV-related PCNSL differs from IC-PCNSL in terms of pathological characteristics including METTL3, Bcl-2, p53 and EBER. We therefore suggest that the pathogenesis of HIV-related PCNSL and IC-PCNSL may differ according to host immune status.

AB021. Primary diffuse large B-cell lymphoma of the central nervous system: role of imaging in a rare disease-a case report.

BACKGROUND: Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) constitutes approximately 1-3% of primary CNS tumors. This rare CNS tumor presents diverse clinical manifestations and variable imaging characteristics, making its diagnosis challenging using radiological modalities alone. Recognizing the role of imaging in different stages of treatment and understanding the various imaging patterns and radiological features is crucial for timely diagnosis and appropriate therapeutic decision-making. CASE DESCRIPTION: A 62-year-old woman presented to our tertiary hospital with a 1-month history of left-sided headache and left hemiparesis. A computed tomography (CT) scan from a previous hospital revealed a space-occupying lesion in the right temporo-occipital region with signs of increased intracranial pressure but no evidence of hemorrhage or calcifications. Subsequent magnetic resonance imaging (MRI) demonstrated a solid intra-axial lesion in the right temporoparietooccipital region, which exhibited heterogeneous enhancement with diffusion restriction. The lesion appeared hypointense on T1-weighted and hyperintense on T2-fluid attenuated inversion recovery (T2-FLAIR) sequence, containing cystic components surrounded by edema and causing compression of the occipital horn of the right lateral ventricle without midline shift. Immunohistochemical analysis confirmed the diagnosis of high-grade DLCBL. The patient underwent surgical resection followed by chemotherapy. A follow-up MRI revealed a new lesion in the right temporoparietooccipital region, which had increased in size, suggestive of lymphoma recurrence. The variable radiological presentations of primary CNS lymphoma (PCNSL) can often mimic other pathologies, such as gliomas, infections, abscesses, and secondary lymphomas, making it a diagnostic challenge. The imaging findings in this case align with the typical features of PCNSL. Both initial and follow-up imaging played a crucial role in guiding therapeutic decisions and assessing treatment response. CONCLUSIONS: This case report underscores the importance of recognizing the imaging characteristics of primary DLBCL of the CNS. Timely and accurate diagnosis based on imaging patterns is essential for expediting therapeutic decisions and evaluating the efficacy of treatment interventions, ultimately improving patient outcomes.

AB080. High-dose methotrexate with and without intra-thecal methotrexate and whole-brain radiotherapy for primary central nervous system lymphoma: a systematic review.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) requires effective & well-tolerated treatment strategies. The use of high-dose methotrexate (HD-MT) with or without intra-thecal methotrexate (IT-MT) and whole-brain radiotherapy (WBRT) has emerged as a prominent approach for PCNSL. This systematic review aims to assess the efficacy and safety of these treatment modalities. METHODS: A comprehensive search strategy identified relevant studies from PubMed, EMBASE, and Cochrane Library. The following search terms were used: "high-dose methotrexate", "primary central nervous system lymphoma", "intra-thecal methotrexate", and "whole-brain radiotherapy". We included randomized controlled trials (RCTs), cohort studies & case-controlled studies evaluating the use of HD-MT with or without IT-MT and whole-brain radiotherapy in the treatment of confirmed PCNSL. Data extraction & quality assessment was conducted by two independent reviewers. Primary outcomes include overall survival (OS), progression-free survival (PFS) & treatment-related adverse events (TRAEs). Secondary outcomes were neurological function and quality of life (QOL) assessments. The risk of bias in individual studies was assessed using the Cochrane Risk of Bias Tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. RESULTS: We identified 5 studies, consisting of 1 RCT, 3 cohort studies, and 1 case-controlled study. Pooled analysis revealed that HD-MT with or without IT-MT and whole-brain radiotherapy significantly improved both OS and PFS compared to other treatment modalities but we found no significant difference between patients who received HD-MT with or without IT-MT. Combination therapy was generally well-tolerated, with manageable TRAE. Subgroup analyses stratified by age, disease stage, and other relevant factors demonstrated consistent efficacy and safety profiles across different patient populations. The risk of bias assessment indicated that the majority of the included studies had low-moderate risk of bias. CONCLUSIONS: There was no significant difference between patients who received HD-MT with or without IT-MT plus radiotherapy, emphasizing the comparable efficacy of these treatment modalities. Combination therapy was generally well-tolerated, with manageable TRAE. This highlights the favourable safety profile of HD-MT with fewer side effects compared with the combination of IT-MT.

AB079. Whole-brain radiotherapy versus high dose chemotherapy with autologous stem-cell transplantation for consolidation therapy in primary central nervous system lymphoma.

BACKGROUND: Whole brain radiotherapy (WBRT) is commonly used as consolidation therapy in primary central nervous system lymphoma (PCNSL). However, high-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) has emerged as an alternative approach for PCNSL. This systematic review aims to assess the efficacy and safety of both treatment modalities. METHODS: The systematic review follows PRISMA guidelines. A comprehensive search strategy identified relevant studies from PubMed, Europe PMC, and Cochrane Library. The following search terms were used: "primary central nervous system lymphoma", "Autologous Stem Cell Transplantation", and "whole-brain radiotherapy". We included randomized controlled trials (RCTs) cohort studies evaluating the use of whole-brain radiotherapy and high-dose chemotherapy followed by autologous stem cell transplantation in the treatment of histologically-confirmed PCNSL. Publications included were limited to English language full texts that were published in the past 10 years. Data extraction & manuscript quality assessment was done by two independent reviewers with a third reviewer to resolve any discrepancy. Primary outcomes include overall survival (OS), progression-free survival (PFS) & treatment related toxicity (TRT). Secondary outcomes were clinical neurological function and performance score assessments. Individual studies were assessed using the Jadad Scale and the Newcastle-Ottawa Scale for observational studies. RESULTS: We identified 5 studies, consisting of 2 RCTs and 3 cohort studies. After all studies considered, analysis revealed that consolidation therapy with HD-ASCT had a better overall PFS and OS compared to whole-brain radiotherapy (P<0.005). Both groups showed similar TRT with mostly haematological toxicity. Holistically clinical cognitive functions are found to be improved in HD-ASCT Patients and poorer results are exhibited by WBRT patients primarily in executive functions. Performance statuses are scored differently across all studies with slightly preferable results shown in patients treated with HDC-ASCT. CONCLUSIONS: Based on the findings of this systematic review, HDC-ASCT might be a preferable choice of consolidative therapy as shown with better OS, PFS with similar TRT. While WBRT are more feasible and cost-efficient, risks of cognitive impairment and reduced performance status after WBRT should be considered for further treatment choices. Further randomized clinical trials with a similar scoring system are needed.

Primary Central Nervous System Lymphoma Presenting as a Solitary Fourth Ventricular Mass: A Case Report.

The occurrence of primary fourth ventricular lymphoma is an exceptionally uncommon phenomenon. Here, we present a case of lymphoma in the fourth ventricle in a 30-year-old male who presented with progressive headache and vertigo over the last one month of his presentation. Preoperative MRI revealed a space-occupying lesion of the fourth ventricle. Pathological analysis following complete resection confirmed the lesion as primary central nervous system lymphoma. The patient underwent chemotherapy following the MTR (methotrexate, temozolomide, and rituximab) protocol with four months of uneventful follow-up, indicating no disease recurrence. Therefore, clinicians are advised to consider the potential presence of lymphoma as part of the differential diagnosis for space-occupying lesions, especially when there is a combination of clinical deterioration and rapid imaging progression.

Targeted multiplex validation of CSF proteomic biomarkers: implications for differentiation of PCNSL from tumor-free controls and other brain tumors.

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin's lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation. Methods: CSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels. Results: Final proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features. Discussion: This study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.

Predictors for the Differentiation between Glioblastoma, Primary Central Nervous System Lymphoma, and Metastasis in Patients with a Solitary Enhancing Intracranial Mass.

Introduction Differentiation between glioblastoma (GBM), primary central nervous system lymphoma (PCNSL), and metastasis is important in decision-making before surgery. However, these malignant brain tumors have overlapping features. This study aimed to identify predictors differentiating between GBM, PCNSL, and metastasis. Materials and Methods Patients with a solitary intracranial enhancing tumor and a histopathological diagnosis of GBM, PCNSL, or metastasis were investigated. All patients with intracranial lymphoma had PCNSL without extracranial involvement. Demographic, clinical, and radiographic data were analyzed to determine their associations with the tumor types. Results The predictors associated with GBM were functional impairment ( p = 0.001), large tumor size ( p < 0.001), irregular tumor margin ( p < 0.001), heterogeneous contrast enhancement ( p < 0.001), central necrosis ( p < 0.001), intratumoral hemorrhage ( p = 0.018), abnormal flow void ( p < 0.001), and hypodensity component on noncontrast cranial computed tomography (CT) scan ( p < 0.001). The predictors associated with PCNSL comprised functional impairment ( p = 0.005), deep-seated tumor location ( p = 0.006), homogeneous contrast enhancement ( p < 0.001), absence of cystic appearance ( p = 0.008), presence of hypointensity component on precontrast cranial T1-weighted magnetic resonance imaging (MRI; p = 0.027), and presence of isodensity component on noncontrast cranial CT ( p < 0.008). Finally, the predictors for metastasis were an infratentorial ( p < 0.001) or extra-axial tumor location ( p = 0.035), smooth tumor margin ( p < 0.001), and presence of isointensity component on cranial fluid-attenuated inversion recovery MRI ( p = 0.047). Conclusion These predictors may be used to differentiate between GBM, PCNSL, and metastasis, and they are useful in clinical management.

Primary central nervous system lymphoma: A mirror type presentation in an immunocompetent patient.

Background: Primary central nervous system (CNS) lymphoma is a very rare extranodal non-Hodgkin lymphoma. The bilateral pattern, as we call it "mirror type", has been identified in other CNS lesions such as gliomas, metastases, and demyelinating lesions, so the differential diagnosis includes imaging studies such as magnetic resonance imaging contrasted with spectroscopy, ruling out immunodeficiency or metastatic disease. Case Description: A 65-year-old female presented progressing headache, loss of memory and language alterations, as well as sensory alterations. Neuroimaging showed the presence of two equidistant periventricular lesions at the level of both ventricular atria, a spectroscopy study suggestive of malignancy. Serological studies showed no evidence of immunodeficiency or the presence of positive tumor markers; however, a biopsy was performed, which revealed a histopathological result of primary lymphoma of the CNS. Conclusion: In neuro-oncology, primary CNS tumors with multiple lesions are rare, even more, the "mirror type" lesions. Lymphomas are lesions that can present in different ways on imaging and clinical presentation. These tumors that present a vector effect due to their size, perilesional edema, or that lead to loss of neurological function are highly discussed in diagnostic and surgical treatment. Due to their prognosis, action on diagnosis and treatment must be taken as quickly as hospital resources allow.

An improved attention module based on nnU-Net for segmenting primary central nervous system lymphoma (PCNSL) in MRI images1.

BACKGROUND: Accurate volumetric segmentation of primary central nervous system lymphoma (PCNSL) is essential for assessing and monitoring the tumor before radiotherapy and the treatment planning. The tedious manual segmentation leads to interindividual and intraindividual differences, while existing automatic segmentation methods cause under-segmentation of PCNSL due to the complex and multifaceted nature of the tumor. OBJECTIVE: To address the challenges of small size, diffused distribution, poor inter-layer continuity on the same axis, and tendency for over-segmentation in brain MRI PCNSL segmentation, we propose an improved attention module based on nnUNet for automated segmentation. METHODS: We collected 114 T1 MRI images of patients in the Huashan Hospital, Shanghai. Then randomly split the total of 114 cases into 5 distinct training and test sets for a 5-fold cross-validation. To efficiently and accurately delineate the PCNSL, we proposed an improved attention module based on nnU-Net with 3D convolutions, batch normalization, and residual attention (res-attention) to learn the tumor region information. Additionally, multi-scale dilated convolution kernels with different dilation rates were integrated to broaden the receptive field. We further used attentional feature fusion with 3D convolutions (AFF3D) to fuse the feature maps generated by multi-scale dilated convolution kernels to reduce under-segmentation. RESULTS: Compared to existing methods, our attention module improves the ability to distinguish diffuse and edge enhanced types of tumors; and the broadened receptive field captures tumor features of various scales and shapes more effectively, achieving a 0.9349 Dice Similarity Coefficient (DSC). CONCLUSIONS: Quantitative results demonstrate the effectiveness of the proposed method in segmenting the PCNSL. To our knowledge, this is the first study to introduce attention modules into deep learning for segmenting PCNSL based on brain magnetic resonance imaging (MRI), promoting the localization of PCNSL before radiotherapy.

Optimising Rehabilitation Strategies for Primary Central Nervous System Neoplasm-Related Neurological Deficits Using a Comprehensive Multimodality Approach Including Robotic Gloves Technology: A Comprehensive Case Report.

This case study examines the rehabilitation strategy for a 51-year-old farmer with primary neoplasm of the central nervous system (CNS)-related hemiparesis, balance issues, and cognitive impairment. Primary neoplasm of the CNS is a rare type of cancer that affects the brain, spinal cord, and other parts of the CNS. Hemiparesis, which is weakness on one side of the body, is a common symptom of primary neoplasm of the CNS. The tumour can cause inflammation and swelling in the brain, which can further contribute to weakness. Symptoms include headaches, confusion, seizures, and changes in vision or speech. The patient underwent surgical excision, chemotherapy, and radiation therapy but faced challenges in physiotherapy. The patient's initial assessment revealed asymmetries and impairments on the right side, including muscle weakness, flexor synergy, trunk imbalance, gait abnormalities, and cognitive impairment. A tailored physiotherapy protocol was implemented, focusing on improving muscle strength, synergy patterns, balance, gait, motor control, speech, and cognitive function. Innovative robotic gloves technology was incorporated to enhance hand functionality. This case study contributes to the growing body of evidence supporting the effectiveness of comprehensive rehabilitation strategies, including innovative technologies, in optimising recovery for individuals with CNS lymphoma-related neurological deficits. Further research and exploration could further validate their benefits and enhance the overall rehabilitation journey for such patients.

Bruton's Tyrosine Kinase Inhibitors in Refractory or Relapsing Primary Central Nervous System Lymphoma: A Meta-analysis and Systematic Review.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma that primarily affects the central nervous system. Current treatments, such as surgery, chemotherapy, and whole-brain radiotherapy, often fail to achieve satisfactory results. The prognosis for patients with refractory or relapsed (R/R) PCNSL is bleak. The optimal treatment for refractory or relapsed PCNSL is poorly defined due to a limited number of studies in this setting. Bruton's tyrosine kinase (BTK) inhibitors, as part of targeted therapy regimens, have undergone testing in several clinical trials against PCNSL and have shown promising results in the treatment of R/R PCNSL. In this meta-analysis, we aim to explore and critically appraise the evidence regarding the efficacy of BTK inhibitors in the treatment of refractory or relapsed PCNSL. METHODS: A systematic search was conducted on multiple databases including PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and CNKI, covering the period up to November 2023. The inclusion criteria for studies were patients with R/R PCNSL who received BTK inhibitors, and reported data on overall response rate (ORR) and complete remission (CR). The pooled rates were calculated using a random-effects or fixed-effects model with a double arcsine transformation, and 95% CIs were determined for all outcomes. RESULTS: In total, 1 studies involving 185 patients were identified and included in the meta-analysis. The pooled complete remission (CR) rate of BTK inhibitors-based treatment for R/R PCNSL was found to be 50%. Subgroup analysis revealed that the CR rates for BTK inhibitor monotherapy, BTK inhibitor combined with chemotherapy, and BTK inhibitor combined with radiotherapy for R/R PCNSL were 7%, 68%, and 80%, respectively. The ORR for BTK inhibitors-based treatment for R/R PCNSL was 70%. Subgroup analysis showed that the ORR rates for BTK inhibitor monotherapy and BTK inhibitor combined with chemotherapy for R/R PCNSL were 55% and 83%, respectively. The most common adverse events (AEs) reported were hematologic AEs, including neutropenia, anemia, and thrombocytopenia. Severe nonhematologic AEs included rash, febrile neutropenia, increased levels of aspartate aminotransferase, and increased blood bilirubin. CONCLUSIONS: BTK inhibitors can be regarded as a safe and effective treatment option for R/R PCNSL, thereby providing a potential new avenue for R/R PCNSL treatment. However, it is important to note that further large-sample prospective randomized controlled trials are needed to validate these findings and establish their wider applicability.

Primary central nervous system lymphoma in elderly: An illustrative case of the new role of surgery and integrative medical management.

Background: Primary central nervous system lymphoma (PCNSL) is a rare, aggressive non-Hodgkin lymphoproliferative neoplasm. Surgery is traditionally limited to biopsy due to past studies, but recent strong evidence continues to challenge this status quo in selected patients. Here, the authors characterize a case to illustrate the potential role of surgery and foster research on integrative medical management approaches for this disease. Case Description: A 73-year-old woman was admitted to the hospital with aphasia and confusion. Neuroimaging suggested a lymphoproliferative process. The patient underwent cytoreductive surgery to resect the lesion. Microscopically, large infiltrating lymphoid cells that induced brain tissue damage were observed, and a diagnosis of diffuse large B-cell lymphoma was made based on immunohistochemistry. The patient evolved clinically post surgery. A complete response to further chemotherapy maintained the patient's clinical recovery. Conclusion: This rare case highlights the potential of surgical intervention in the management of selected patients with PCNSL. The authors also underscore the recent, meta-analytic evidence on surgery followed by combined chemotherapy for the management of specific cases. The reported recovery in an elderly patient is noteworthy and adds to the literature on this rare subtype of brain tumors. Future research should consider investigating a potential profile of candidates for resection and combined chemotherapy in PCNSL.

Age-adjusted high-dose chemotherapy followed by autologous stem cell transplantation or conventional chemotherapy with R-MP as first-line treatment in elderly primary CNS lymphoma patients - the randomized phase III PRIMA-CNS trial.

BACKGROUND: Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is scarce and treatment delivery is challenging due to comorbidities and reduced performance status. High-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) after high-dose methotrexate (MTX)-based immuno-chemotherapy has become an increasingly used treatment approach in eligible elderly PCNSL patients with promising feasibility and efficacy, but has not been compared with conventional chemotherapy approaches. In addition, eligibility for HCT-ASCT in elderly PCNSL is not well defined. Geriatric assessment (GA) may be helpful in selecting patients for the best individual treatment choice, but no standardized GA exists to date. A randomized controlled trial, incorporating a GA and comparing age-adapted HCT-ASCT treatment with conventional chemotherapy is needed. METHODS: This open-label, multicenter, randomized phase III trial with two parallel arms will recruit 310 patients with newly diagnosed PCNSL > 65 years of age in 40 centers in Germany and Austria. The primary objective is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with rituximab, MTX, procarbazine (R-MP) followed by maintenance with procarbazine in terms of progression free survival (PFS). Secondary endpoints include overall survival (OS), event free survival (EFS), (neuro-)toxicity and quality of life (QoL). GA will be conducted at specific time points during the course of the study. All patients will be treated with a pre-phase rituximab-MTX (R-MTX) cycle followed by re-assessment of transplant eligibility. Patients judged transplant eligible will be randomized (1:1). Patients in arm A will be treated with 3 cycles of R-MP followed by maintenance therapy with procarbazine for 6 months. Patients in arm B will be treated with 2 cycles of MARTA (R-MTX/AraC) followed by busulfan- and thiotepa-based HCT-ASCT. DISCUSSION: The best treatment strategy for elderly PCNSL patients remains unknown. Treatments range from palliative to curative but more toxic therapies, and there is no standardized measure to select patients for the right treatment. This randomized controlled trial will create evidence for the best treatment strategy with the focus on developing a standardized GA to help define eligibility for an intensive treatment approach. TRIAL REGISTRATION: German clinical trials registry DRKS00024085 registered March 29, 2023.

Role of Rituximab in Treatment of Patients With Primary Central Nervous System Lymphoma (PCNSL): A Systematic Review and Meta-Analysis.

Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin's lymphoma involving the brain, cerebrospinal fluid, spinal cord and eyes. Rituximab has played a prominent role in the treatment of non-Hodgkin's B-cell lymphomas, including aggressive diffuse large B lymphoma. However, as a macromolecular drug, the role of rituximab in the treatment of PCNSL has been controversial. In this systematic review and meta-analysis, we evaluated the role of rituximab in the treatment of PCNSL. We searched articles in the following electronic databases including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov until October 20, 2022.We included 11 studies (3 RCTS and 8 retrospective studies) with a total of 1182 patients. We extracted the baseline characteristics and outcomes of the studies and assessed the risk of bias, then used Review Manager 5.4 for this meta-analysis. The primary outcomes included complete response rate (CR), overall survival (OS), and progression-free survival (PFS). Odds ratios (ORS) and corresponding 95% confidence intervals (CIS) for the primary outcome were analyzed and compared. The results of our statistical analysis show that the use of rituximab was closely correlated with a higher CR(OR 1.70,95%CI 1.17-2.46, P = .005), 3-year OS (OR 2.40, 95%CI 1.53-3.77, P = .0001), 5-year OS (OR 2.75, 95%CI 1.68-4.49, P < .0001), 3-year PFS(OR 4.42, 95%CI 1.15-16.97, P < .0001), 5-year PFS(OR 1.97, 95%CI 1.39-2.78, P = .0001).These results suggest that rituximab may have a positive impact on the prognosis of patients with PCNSL, and may be helpful in the determination of treatment plan for patients with PCNSL.

Recent advances and challenges in primary central nervous system lymphoma: a narrative review.

Background and Objective: Primary central nervous system lymphoma (PCNSL) is a rare and highly invasive non-Hodgkin lymphoma that is challenging to diagnose and treat. It is typically confined to the brain, spinal cord, and eyes. The diagnosis of PCNSL lacks specificity, and the misdiagnosis and missed diagnosis rates of PCNSL are high. Traditional treatments for PCNSL, such as surgery, whole-brain radiation therapy, high-dose methotrexate-based chemotherapy, and rituximab (RTX), have been associated with higher initial remission rates. However, the duration of any remission is short, the recurrence rate is high, and treatment-related neurotoxicity is strong, which are challenges for medical researchers. This review provides an overview of and perspectives on the diagnosis, treatment, and evaluation of patients with PCNSL. Methods: The PubMed database was searched to retrieve articles published from January 1, 1991, to June 2, 2022 using the following Medical Subject Headings (MeSH) terms: "Primary central nervous system lymphoma" and "clinical trial". The American Society of Clinical Oncology and the National Comprehensive Cancer Network guidelines were also reviewed to obtain additional information. The search was limited to articles published in English, German, and French. In total, 126 articles were deemed eligible for inclusion in this study. Key Content and Findings: In terms of the diagnosis of PCNSL, a combination of flow cytometry and cytology has been shown to improve the diagnostic accuracy of PCNSL. Additionally, interleukin 10 and chemokine C-X-C motif ligand 13 are promising biomarkers. In terms of the treatment of PCNSL, programmed death-1 (PD-1) blockage and chimeric antigen receptor T cell (CAR-T) therapy treatments have shown prospective efficacy, but more clinical trials need to be conducted to gather further evidence. We also reviewed and summarized prospective clinical trials on PCNSL. Conclusions: PCNSL is a rare and highly aggressive lymphoma. The treatment of PCNSL has progressed significantly, and while the survival of patients has improved, relapse and low long-term survival remain huge challenges. Continuous in-depth research is being conducted on new drug therapies and combination therapies for PCNSL. A combination of targeted drugs (e.g., ibrutinib, lenalidomide, and PD-1 monoclonal antibody) and traditional therapy represents the main research direction for future PCNSL treatments. CAR-T has also shown great potential in the treatment of PCNSL. With the development of these new diagnostic and therapeutic methods and further research into the molecular biology of PCNSL, patients with PCNSL should achieve a better prognosis.

Is more better? Increased doses of high dose methotrexate and addition of rituximab is associated with improved outcomes in a large primary CNS lymphoma cohort.

Background: Primary central nervous system lymphoma (PCNSL) is a rare and aggressive primary brain tumor. While high dose methotrexate (HDMTX) regimens remain standard of care, it remains unclear if optimization of HDMTX doses and the addition of rituximab provide clinical benefit. Over the last 30 years, standard care given at Memorial Sloan Kettering Cancer Center (MSKCC) has evolved, allowing the comparison of patients receiving different numbers of HDMTX doses and those treated with and without rituximab. The purpose of this study was to describe outcomes based on treatment pattern changes. Methods: This single-center, retrospective, IRB-approved study at MSKCC included patients with immunocompetent PCNSL, age ≥18 years and diagnosed between 1/1983-12/2017. Overall survival (OS) was modeled from date of last HDMTX for analyses associating HDMTX and OS. Multivariable Cox regression models estimated hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results: There were 546 patients identified with newly diagnosed PCNSL. Median overall survival (mOS) of the entire population was 4.7 years (95% CI: 3.8-5.7 years); 3.3 years (95% CI: 2.7-3.9 years) in patients diagnosed prior to 2006 and 8.1 years (95% CI: 6.6-11.1 years) in patients diagnosed 2006 onwards. Patients receiving ≥6 doses of HDMTX had improved survival compared to those receiving <6 doses of HDMTX (mOS: 7.8 vs. 4.3 years; P=0.001). Patients receiving induction rituximab had improved OS compared to those who did not receive rituximab (mOS: 10.5 vs. 3.2 years; P<0.0001). Patients receiving ≥6 doses of HDMTX and rituximab had greatest mOS at 13 years, with a 70% reduction in death (HR =0.30; 95% CI: 0.19-0.47) adjusting for treatment era, sex, and recursive partitioning analysis (RPA) classes comprising age and karnofsky performance score (KPS). Conclusions: OS for PCNSL has improved significantly over the last few decades. Patients seem to benefit with ≥6 doses of HDMTX and the addition of rituximab, an effect independent of treatment era, age, and KPS.

Stereotactic Radiosurgery for Primary Central Nervous System Lymphoma.

Background Primary central nervous system lymphoma (PCNSL) is rare, with a treatment backbone that typically includes high-dose methotrexate-based chemotherapy, with radiation often reserved for persistent or progressive disease. In this study, we report the outcomes of stereotactic radiosurgery (SRS) in patients with PCNSL to potentially defer whole brain radiotherapy (WBRT) or as salvage after WBRT. Methodology We performed a single-institution, retrospective review of 20 patients with PCNSL who received single-fraction or fractionated SRS to 32 lesions between September 1992 and July 2019. Results The median age at SRS was 67 years (interquartile range (IQR) = 56-74 years). The median Karnofsky Performance Status (KPS) at SRS was 80 (IQR = 50-80). In total, 18 (90%) patients received methotrexate-based chemotherapy prior to SRS, with a median of eight cycles (IQR = 5-10). A total of 10 patients received SRS for recurrent disease after chemotherapy and/or WBRT, nine patients received SRS for the persistent disease after chemotherapy alone, and one patient received up-front SRS. Overall, five patients received SRS following WBRT. The median SRS dose was 16 Gy (IQR = 14-22.5 Gy) in one fraction (IQR = 1-5 fractions). Eight patients (40%) were treated with consolidative pomalidomide or lenalidomide following SRS. The local control rate was 100% (32/32 lesions at a median follow-up of 15 months). In total, 13 of 16 (81%) patients with available follow-up experienced distant brain recurrence. The median time to distant failure following SRS was 10 months (IQR = 1-16 months). Three patients received salvage SRS, and three patients received salvage WBRT. The median overall survival from diagnosis was 39 months (95% confidence interval = 24-54 months). KPS at the time of SRS was significantly correlated with time to progression (p = 0.002). The use of lenalidomide or pomalidomide after SRS was associated with improved overall survival after SRS (three vs. 14 months, p = 0.035). Consolidative etoposide and cytarabine after initial methotrexate-based chemotherapy was also associated with improved survival following SRS (eight vs. 47 months, p = 0.028). Conclusions SRS offers effective local tumor control for patients with PCNSL; however, the majority of patients experience distant progression. SRS may have a role in the salvage setting for patients with recurrence after WBRT, or allow deferral of WBRT in select patients, although systemic therapy appears to strongly influence outcomes in this cohort.

Primary central nervous system lymphoma presenting as an isolated intramedullary spinal cord lesion: a case report.

Background: Intramedullary spinal cord lesions prove to be a diagnostic challenge due to their non-specific clinical and radiological presentation. There is a preference for empiric medical therapy, given the inherent risks of surgical intervention to the spine. These factors can lead to delay in diagnosis. Primary central nervous system lymphoma is a rare cause and presents with atypical features in the immunosuppressed patient, including a lack of response to steroid therapy. Case Description: We present a 64-year-old male patient with underlying sarcoidosis who reported progressive neuropathy with imaging showing a spinal cord lesion. Based on the above, multiple courses of empiric therapy were employed, including systemic steroids, chemotherapy and immunotherapy. Despite this, there was further clinical deterioration and interim imaging showed disease progression. The decision was made to perform open biopsy of the spinal cord lesion to aid diagnosis. Histological analysis diagnosed Epstein-Barr virus (EBV)-positive high grade large B-cell lymphoma. The patient received rituximab and methotrexate with radiological response but no clinical benefit. He continued to suffer treatment-related complications including encephalopathy and recurrent infections which eventually lead to death. Conclusions: Primary central nervous system lymphoma is an aggressive disease and failure to respond to empiric treatment should prompt clinician's to consider biopsy for definitive diagnosis. A lack of response to steroids does not exclude lymphoma.

Clinical pathology of primary central nervous system lymphoma in HIV-positive patients-a 41 Chinese patients retrospective study.

OBJECTIVES: The purpose of this study was to investigate the clinicopathological characteristics of primary central nervous system lymphoma (PCNSL). METHODS: We collected 41 PCNSL formalin-fixed, paraffin-embedded (FFPE) samples from human immunodeficiency virus (HIV)-positive patients and performed HE (haematoxylin-eosin) staining, immunohistochemistry (IHC) staining, in situ hybridization, fluorescence in situ hybridization (FISH). Real-time quantitative polymerase chain reaction (RT-qPCR) was performed in 9 cases of FFPE samples. Meanwhile, we analysed the clinical pathological significance of the results. RESULTS: Seven patients had diffuse large B-cell lymphoma (DLBCL) with germinal centre B-cell (GCB)-like DLBCL, 32 had activated B-cell (ABC)-like DLBCL, and 2 had Burkitt lymphoma (BL). GCB-like DLBCL patients were older at onset (P = 0.040).A lower CD4+ T-cell count and a decrease in cerebrospinal fluid (CSF) glucose content were more frequent in ABC-like DLBCL (P = 0.012, P = 0.006). Overexpression of P53 was more in ABC-like DLBCL (P = 0.041). 73.2 % cases were Epstein-Barr encoding region (EBER) positive, which was more likely in ABC-like DLBCL patients (P = 0.037). EBV DNA were detected in 5/7 EBER-negative DLBCL cases and none (0/2) of the BL cases. All the cases were negative for HHV8 staining. None of the 7 Double expressor lymphoma (DEL) cases had BCL2, BCL6, or c-MYC genetic rearrangements. CONCLUSIONS: HIV-related PCNSL showed unique clinical pathological significance. None of EBV detected in HIV-related BL and without HHV8 infectious are new sights in our single-center study of Chinese HIV-related PCNSL patients.

Primary Central Nervous System Lymphoma Mimicking the Presentation of Pituitary Apoplexy: A Case Report.

Pituitary lymphoma is one of the rare variants of primary central nervous system lymphoma (PCNSL), mostly arising due to the metastatic spread of systemic lymphoma. We report the case of a 69-year-old woman who initially presented to her family physician with a headache but without any other symptoms. The MRI scan revealed a sellar mass consistent with a pituitary macroadenoma. When the patient was referred to our hospital, two weeks later, the symptoms had progressed, comprising complete right-sided ophthalmoplegia and ptosis, with left-sided amaurosis. A repeat MRI revealed an increased size of the sellar mass, consistent with pituitary apoplexy. A right pterional craniotomy with partial resection of the mass was performed and an intraoperative frozen section biopsy was carried out. The final pathology revealed diffuse large B-cell lymphoma. A systemic follow-up including a whole-body CT, bone marrow aspiration, and cerebrospinal fluid studies ruled out any systemic manifestation, and the patient was HIV-negative. The patient underwent treatment with methotrexate, cytarabine, thiotepa, and rituximab for PCNSL. Although rare, PCNSL can mimic pituitary apoplexy, which needs to be considered if conservative therapy or surgery is to be offered to a patient with a radiological and clinical diagnosis of pituitary apoplexy.