Reliable intraoperative diagnostic methods for PCNSL: utility of combining intraoperative immunohistochemistry, cytology, and flow cytometry in achieving optimal treatment.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rapidly growing malignant tumor that typically shows sensitivity to high-dose methotrexate-based chemotherapy. Rapid diagnosis and early chemotherapy are thus essential to obtain the best outcome. To accomplish this, we have performed intraoperative rapid immunohistochemistry (IHC) as an examination method for obtaining accurate diagnosis during surgery. Here, to markedly enhance the accuracy of intraoperative rapid IHC, the utility of adding intraoperative rapid examinations of cytology and flow cytometry (FCM) in addition to rapid IHC was investigated. METHODS: From April 2020 to January 2024, we performed intraoperative rapid IHC in 35 patients with intracranial lesions, including PCNSL. In the last 17 of these cases, intraoperative cytology and FCM were also performed simultaneously. We examined the utility of examination methods in determining treatment strategies for brain tumors, particularly early therapeutic intervention for PCNSL. RESULTS: Postoperative final pathological diagnoses from paraffin-embedded sections were as follows: 20 PCNSLs, 9 glioblastomas, 4 diffuse gliomas, 1 meningioma, and 1 inflammatory disorder. In all cases, results from intraoperative rapid IHC were consistent with final pathological diagnoses from paraffin-embedded sections. In two cases, results from conventional intraoperative rapid pathological diagnoses based on morphological assessments using frozen sections changed with the addition of intraoperative rapid IHC. Further, the time from surgery to initiation of chemotherapy for PCNSL was significantly reduced by adding cytology and FCM to rapid IHC alone (only rapid IHC group: 7.3 days, combination group: 1.6 days; p = 0.015). CONCLUSIONS: The combination of rapid intraoperative IHC, cytology, and FCM contributes to deciding appropriate treatment strategies and facilitating early initiation of chemotherapy for PCNSL. These examination methods may allow new therapeutic strategies for not only PCNSL, but also other brain tumors.

Comment on, "Creactive protein levels, the prognostic nutritional index, and the lactate dehydrogenasetolymphocyte ratio are important prognostic factors in primary central nervous system lymphoma: a singlecenter study of 223 patients".

This study by Zuo et al. (2024) investigates the prognostic significance of C-reactive protein (CRP) levels, the prognostic nutritional index (PNI), and the lactate dehydrogenase-to-lymphocyte ratio (LLR) in primary central nervous system lymphoma (PCNSL) using data from 223 patients. The research demonstrates that these markers are critical in predicting patient outcomes, offering novel insights beyond traditional prognostic models like the MSKCC and IELSG scores. Despite its strengths, the study's retrospective design and lack of validation cohort limit its generalizability. Future research should focus on validating these findings in diverse, multicenter settings and integrating these markers with existing prognostic models to improve clinical decision-making. Longitudinal studies and advanced statistical methods are recommended to further explore the interactions between these factors and their impact on patient outcomes, potentially leading to the development of targeted therapies for PCNSL.

Characterizing second line and beyond therapies for primary central nervous system lymphomas.

Primary central nervous system (CNS) lymphoma (PCNSL) is a rare and aggressive lymphoma that affects the CNS without other systemic involvement. High-dose methotrexate (HDMTX)-based regimens are recommended frontline treatment, followed by consolidation with either high-dose chemotherapy, whole brain radiation (WBRT) +/- sequential temozolomide (TMZ), or autologous stem cell transplant (autoSCT). Despite advancements with HDMTX and rituximab, up to half of patients will relapse. Treatment for relapsed or refractory (R/R) disease varies widely as preferred regimens are not well-established. Our study aimed to provide real-world characterization of R/R PCNSL therapies. The secondary objective was characterization of consolidation methods after frontline treatment. This retrospective, descriptive analysis included 54 adult PCNSL patients that received a HDMTX-based frontline regimen between 4/1/2016 and 7/1/2022. Patients receiving HDMTX for the purpose of secondary CNS lymphoma, non-B cell origin PCNSL, and intraocular lymphoma were excluded. Thirty-one patients (57%) received consolidation therapy with rituximab and high-dose cytarabine (R-HDAC), WBRT, or both. Thirteen patients (24%) proceeded with autoSCT. Twenty-five patients had disease progression, with 17 patients receiving second line treatment. The second line treatments were WBRT (24%), clinical trial (18%), rituximab with lenalidomide (R2; 18%), re-induction with HDMTX-based regimens (18%), ibrutinib with rituximab (12%) and R-HDAC (12%). Seven patients progressed, and all received third line treatment. Treatments varied, including R2; ibrutinib +/- HDMTX; rituximab, methotrexate, and cytarabine; R-HDAC; R-nivolumab; and WBRT. Five patients received a fourth line regimen of R +/- lenalidomide, R-HDMTX, or nivolumab monotherapy. Regimens used for the three patients who received fifth line treatment and beyond included R-TMZ and pembrolizumab monotherapy in addition to previously described regimens. Regimen selection is varied and highly dependent on physician preference and patient factors, including clinical trial eligibility, prior therapies, performance status, organ function, and treatment intent. Prospective clinical trials are needed to guide optimal management.

Radiomic prediction for durable response to high-dose methotrexate-based chemotherapy in primary central nervous system lymphoma.

BACKGROUND: The rarity of primary central nervous system lymphoma (PCNSL) and treatment heterogeneity contributes to a lack of prognostic models for evaluating posttreatment remission. This study aimed to develop and validate radiomic-based models to predict the durable response (DR) to high-dose methotrexate (HD-MTX)-based chemotherapy in PCNSL patients. METHODS: A total of 159 patients pathologically diagnosed with PCNSL between 2011 and 2021 across two institutions were enrolled. According to the NCCN guidelines, the DR was defined as the remission lasting ≥1 year after receiving HD-MTX-based chemotherapy. For each patient, a total of 1218 radiomic features were extracted from prebiopsy T1 contrast-enhanced MR images. Multiple machine-learning algorithms were utilized for feature selection and classification to build a radiomic signature. The radiomic-clinical integrated models were developed using the random forest method. Model performance was externally validated to verify its clinical utility. RESULTS: A total of 105 PCNSL patients were enrolled after excluding 54 cases with ineligibility. The training and validation cohorts comprised 76 and 29 individuals, respectively. Among them, 65 patients achieved DR. The radiomic signature, consisting of 8 selected features, demonstrated strong predictive performance, with area under the curves of 0.994 in training cohort and 0.913 in validation cohort. This signature was independently associated with the DR in both cohorts. Both the radiomic signature and integrated models significantly outperformed the clinical models in two cohorts. Decision curve analysis underscored the clinical utility of the established models. CONCLUSIONS: This radiomic signature and integrated models have the potential to accurately predict the DR to HD-MTX-based chemotherapy in PCNSL patients, providing valuable therapeutic insights.

Impact of Postoperative Chemotherapy on Survival in Patients with Primary Central Nervous System Lymphoma: A Study Based on the SEER Database.

Aims/Background We aimed to investigate the impact of postoperative chemotherapy (POCT) on survival in patients with primary central nervous system lymphoma (PCNSL) using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods This study included 786 PCNSL patients, of which 605 received chemotherapy after surgery, and 181 did not. Data from the SEER registry database (2007-2020) were used to analyze PCNSL. Baseline information, including age, sex, race, marital status, primary tumour site, histological type, summary stage, surgical procedures, chemotherapy, and radiotherapy, was analyzed. Propensity Score Matching (PSM) (1:1) was employed to balance the effects of confounding variables between the two groups. Subsequently, Cox regression and bidirectional stepwise regression were used to identify independent prognostic factors. Kaplan-Meier (K-M) survival curves were constructed to assess the impact of POCT on patient prognosis. Additionally, two cases of PCNSL with typical magnetic resonance imaging appearances were presented. Results Multivariate Cox regression results revealed that age older than 60 years (hazard ratio [HR] = 1.786; 95% confidence interval [CI]: 1.272-2.509; p = 0.001) and absence of POCT (HR = 2.841; 95% CI: 2.159-3.738; p < 0.001) were independent prognostic risk factors, while primary tumour locations in the meninges (HR = 0.136; 95% CI: 0.032-0.569; p = 0.006) and other nervous system regions (HR = 0.552; 95% CI: 0.326-0.936; p = 0.027), as well as histological morphologies such as diffuse large B-cell lymphoma (HR = 0.233; 95% CI: 0.128-0.425; p < 0.001) and non-Hodgkin lymphoma (HR = 0.559; 95% CI: 0.356-0.876; p = 0.011), were associated with favourable patient outcomes. K-M curves demonstrated that the group undergoing POCT had a significantly more favourable prognosis compared to the non-POCT group, before (HR = 0.454; 95% CI: 0.343-0.600; p < 0.0001) or after PSM (HR = 0.580; 95% CI: 0.431-0.780; p < 0.0001). For patients with PCNSL, those with tumours located in the infratentorial region (HR = 0.231; 95% CI: 0.078-0.682; p = 0.046), supratentorial region (HR = 0.250; 95% CI: 0.163-0.383; p < 0.0001), overlapping brain regions (HR = 0.201; 95% CI: 0.056-0.727; p = 0.0058), and those who underwent biopsy (HR = 0.740; 95% CI: 0.463-1.182; p = 0.003), subtotal resection (STR) (HR = 0.490; 95% CI: 0.265-0.906; p = 0.0064), or gross total resection (GTR) (HR = 0.613; 95% CI: 0.292-1.287; p = 0.0003) had better prognoses in the postoperative chemotherapy group compared to the non-chemotherapy group. Conclusion POCT significantly improves the prognosis of PCNSL patients and identifies the characteristics of the benefiting population. This information aids clinical practitioners in designing personalized treatment plans for individuals and advancing precise treatment.

Early Urinary Potassium Level Predicts High-dose Methotrexate Elimination Delay in Primary Central Nervous System Lymphoma.

BACKGROUND/AIM: Treatment of primary central nervous system lymphoma (PCNSL) includes high dose methotrexate-based polychemotherapy (HD-MTX). This study aimed to identify early predictive factors of methotrexate (MTX) delayed elimination. PATIENTS AND METHODS: We prospectively included all patients with newly-diagnosed PCNSL. Daily serum and urinary creatinine and ionogram were collected. We generated two independent cohorts: a training cohort (TC) and a confirmatory cohort (CC). RESULTS: We included for analysis 64 cures of HD-MTX (20 patients) in the TC and 59 cures (22 patients) in the CC. Median elimination time of MTX was 95 h and 96 h in the TC and CC, respectively. In multivariate analysis, older age (p=0.004), low Karnofsky Performance Status (p=0.036) and high urinary K+ (p=0.001) were associated with delayed MTX elimination. An optimal cutoff for urinary K+ was defined. In the CC, we confirmed that high urinary K+ (p=0.004) remained associated with delayed MTX elimination. CONCLUSION: High urinary K+ may be predictive of delayed MTX elimination in primary central nervous system lymphoma. Its relevance as a decision-making factor needs to be validated in additional prospective studies.

MYD88 mutation-positive indolent B-cell lymphoma with CNS involvement: Bing-Neel syndrome mimickers.

MYD88 p.L265P mutation occurs in over 90% of Waldenström's macroglobulinemia (WM), which is characterized by lymphoplasmacytic lymphoma (LPL) with monoclonal IgM. WM requires careful diagnosis due to overlapping features with other B-cell malignancies. Bing-Neel syndrome (BNS), a rare complication of WM, involves central nervous system (CNS) invasion. This report describes two cases of morphologically low-grade B-cell lymphoma in the bone marrow accompanied by the presence of a large B-cell lymphoma in the brain and a common MYD88 p.L265P mutation, which were eventually established as BNS mimickers. Although the two components in these cases showed the same identical light-chain restriction, different immunoglobulin heavy-chain rearrangement peaks indicated distinct lymphoma stem cells for CNS and bone marrow lesions. These clinical cases emphasize the challenges in diagnosing BNS. Based on the findings, biopsy is recommended for accurate identification of the clonal relationship and MYD88 mutation status.

Simultaneous Determination of Methotrexate Concentrations in Human Plasma and Cerebrospinal Fluid Using Two-Dimensional Liquid Chromatography: Applications in Primary Central Nervous System Lymphoma.

Background: In this study, we aimed to develop a method for the simultaneous quantification of methotrexate (MTX) samples extracted from human plasma and cerebrospinal fluid (CSF), using two-dimensional liquid chromatography (2D-LC). Furthermore, we intended to verify whether intravenous mannitol could increase MTX concentration in the CSF of patients. Methods: The mobile phase of PUMP1 consisted of 10.0 mmol/L ammonium acetate and acetonitrile. PUMP2 solution consisted of an aqueous solution of 10.0 mmol/L ammonium acetate. The mobile phase of PUMP3 comprised 50.0 mmol/L ammonium acetate and acetonitrile, with a flow rate of 1.0 mL/min. Results: The developed method was successfully employed to simultaneously determine drug levels in plasma and CSF from the patients treated with MTX. CSF samples were obtained by lumbar puncture 0.5 - 2 h after starting the high-dose methotrexate (HD-MTX) infusion (over 4 h) and immediately before the intrathecal (IT) administration of MTX. Venous blood samples were drawn 4 h after the start of infusion. The calibration curve was linear, with a range of 0.07 - 2.38 µmol/L for CSF samples and a range of 0.11 - 5.51 µmol/L for plasma samples. Precision (> 95%) and accuracy (> 97%) were within the acceptance criteria for each quality control (QC) level. Inter- and intra-day accuracy and precision values met the acceptance criteria for each QC level. The correlation between MTX concentrations in the plasma and CSF was moderate (r = 0.502). No significant difference was observed in MTX concentration in CSF between patients using intravenous mannitol and those not using intravenous mannitol (P = 0.682). Conclusion: The developed method was useful for therapeutic drug monitoring of MTX and suitable for assessing the risks and benefits of chemotherapy in patients with primary central nervous system lymphoma. Intravenous mannitol did not increase MTX concentration in the CSF of patients.

Phase IB part of LOC-R01, a LOC network non-comparative randomized phase IB/II study testing R-MPV in combination with escalating doses of lenalidomide or ibrutinib for newly diagnosed primary central nervous system lymphoma (PCNSL) patients.

BACKGROUND: Results of conventional induction chemotherapies in primary central nervous system lymphoma (PCNSL) need to be improved. Ibrutinib, a BTK inhibitor, and lenalidomide, an immunomodulatory drug, have shown promising results at relapse, supporting to further assess their individual use in combination with high-dose methotrexate-based chemotherapy. METHODS: Patients with newly diagnosed PCNSL were randomized to receive four 28-day cycles of ibrutinib or lenalidomide in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine and prednisone) in a 3 + 3 design. Responders then received a consolidation with R-Cytarabine and an intensive chemotherapy with autologous stem cell transplantation. The objective of the phase IB study was to define the recommended phase II dose (RP2D) based on the dose-limiting toxicity (DLT) occurring during the first induction cycle. RESULTS: Twenty-six patients (median age 52) were randomized. Four DLTs were observed: one grade 5 aspergillosis and pneumocystosis, one grade 4 catheter-related infection and two grade 3 increased alanine aminotransferase levels. RP2D of ibrutinib and lenalidomide were 560 mg daily (D3-14 and D17-28) and 15 mg daily (D1-21) respectively, in combination with R-MPV. In both arms, the most frequent grade ≥3 treatment-related adverse events were hepatic cytolysis, neutropenia and infections. One grade 4 Lyell's syndrome was reported at cycle 2 in the lenalidomide arm. After 4 induction cycles, the overall response rates were 76.9% and 83.3% in the lenalidomide and ibrutinib arm, respectively. CONCLUSION: Targeted induction therapies combining lenalidomide or ibrutinib with R-MPV are feasible for first-line PCNSL. The safety profile is consistent with the known safety profiles of R-MPV and both targeted therapies. The phase II part of the study is ongoing. TRIAL REGISTRATION: NCT04446962.

Comparison of various treatment modalities in patients with primary vitreoretinal lymphoma: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis investigated different treatment modalities' effect on the risk of central nervous system lymphoma progression, ocular disease relapse, systemic lymphoma development and overall survival in primary vitreoretinal lymphoma patients. METHODS: PubMed, EMBASE, Scopus and the Cochrane Library of clinical trials were searched from inception to April 21, 2024. Cohort, cross-sectional and case series studies were included. Methodological quality was assessed using the NIH quality assessment tools. Heterogeneity between studies was assessed using Chi square test and I2 statistic. Outcomes were pooled as odds ratios (OR) using fixed-effects models. Risk of publication bias was assessed using a funnel plot. RESULTS: Included were 28 studies with 476 participants. Ocular treatments included intravitreal methotrexate and/or rituximab injections and ocular radiotherapy. Systemic treatments included intravenous and/or intrathecal chemotherapy, whole-brain radiotherapy and autologous stem cell transplantation. Ocular treatment alone, as compared to systemic or combined treatment, resulted in significantly lower risk of central nervous system lymphoma development (OR = 0.54, p = 0.02) and in no significant difference in the risk for progression to systemic disease (OR = 0.38, p = 0.30) or in overall survival. Significantly lower risk of ocular relapse was found in patients receiving ocular or combined therapy as compared to systemic therapy alone (OR = 0.26, p = 0.001). A subgroup analysis, comparing ocular treatment alone and combined treatment, found no significant difference regarding the risk of central nervous system or systemic lymphoma progression, ocular disease relapse and overall survival. CONCLUSIONS: No benefit was observed for the addition of systemic therapy to ocular treatment in patients with primary vitreoretinal lymphoma.

Differentiation between multifocal CNS lymphoma and glioblastoma based on MRI criteria.

PURPOSE: Differentiating between glioblastoma (GB) with multiple foci (mGB) and multifocal central nervous system lymphoma (mCNSL) can be challenging because these cancers share several features at first appearance on magnetic resonance imaging (MRI). The aim of this study was to explore morphological differences in MRI findings for mGB versus mCNSL and to develop an interpretation algorithm with high diagnostic accuracy. METHODS: In this retrospective study, MRI characteristics were compared between 50 patients with mGB and 50 patients with mCNSL treated between 2015 and 2020. The following parameters were evaluated: size, morphology, lesion location and distribution, connections between the lesions on the fluid-attenuated inversion recovery sequence, patterns of contrast enhancement, and apparent diffusion coefficient (ADC) values within the tumor and the surrounding edema, as well as MR perfusion and susceptibility weighted imaging (SWI) whenever available. RESULTS: A total of 187 mCNSL lesions and 181 mGB lesions were analyzed. The mCNSL lesions demonstrated frequently a solid morphology compared to mGB lesions, which showed more often a cystic, mixed cystic/solid morphology and a cortical infiltration. The mean measured diameter was significantly smaller for mCNSL than mGB lesions (p < 0.001). Tumor ADC ratios were significantly smaller in mCNSL than in mGB (0.89 ± 0.36 vs. 1.05 ± 0.35, p < 0.001). The ADC ratio of perilesional edema was significantly higher (p < 0.001) in mCNSL than in mGB. In SWI / T2*-weighted imaging, tumor-associated susceptibility artifacts were more often found in mCNSL than in mGB (p < 0.001). CONCLUSION: The lesion size, ADC ratios of the lesions and the adjacent tissue as well as the vascularization of the lesions in the MR-perfusion were found to be significant distinctive patterns of mCNSL and mGB allowing a radiological differentiation of these two entities on initial MRI. A diagnostic algorithm based on these parameters merits a prospective validation.

Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group.

BACKGROUND: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. METHODS: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. RESULTS: The most used regimen (46.8%) for GBM in patients aged ≤74 years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). CONCLUSIONS: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.

Multicenter investigation of preoperative distinction between primary central nervous system lymphomas and glioblastomas through interpretable artificial intelligence models.

OBJECTIVE: Research into the effectiveness and applicability of deep learning, radiomics, and their integrated models based on Magnetic Resonance Imaging (MRI) for preoperative differentiation between Primary Central Nervous System Lymphoma (PCNSL) and Glioblastoma (GBM), along with an exploration of the interpretability of these models. MATERIALS AND METHODS: A retrospective analysis was performed on MRI images and clinical data from 261 patients across two medical centers. The data were split into a training set (n = 153, medical center 1) and an external test set (n = 108, medical center 2). Radiomic features were extracted using Pyradiomics to build the Radiomics Model. Deep learning networks, including the transformer-based MobileVIT Model and Convolutional Neural Networks (CNN) based ConvNeXt Model, were trained separately. By applying the "late fusion" theory, the radiomics model and deep learning model were fused to produce the optimal Max-Fusion Model. Additionally, Shapley Additive exPlanations (SHAP) and Grad-CAM were employed for interpretability analysis. RESULTS: In the external test set, the Radiomics Model achieved an Area under the receiver operating characteristic curve (AUC) of 0.86, the MobileVIT Model had an AUC of 0.91, the ConvNeXt Model demonstrated an AUC of 0.89, and the Max-Fusion Model showed an AUC of 0.92. The Delong test revealed a significant difference in AUC between the Max-Fusion Model and the Radiomics Model (P = 0.02). CONCLUSION: The Max-Fusion Model, combining different models, presents superior performance in distinguishing PCNSL and GBM, highlighting the effectiveness of model fusion for enhanced decision-making in medical applications. CLINICAL RELEVANCE STATEMENT: The preoperative non-invasive differentiation between PCNSL and GBM assists clinicians in selecting appropriate treatment regimens and clinical management strategies.

Treatment-related leukoencephalopathy in adults with central nervous system lymphoma: a retrospective analysis of 126 patients.

Neurotoxicity associated with high-dose chemotherapy and whole brain radiotherapy (WBRT) is one of major complications for patients with central nervous system lymphoma (CNSL). Here we determined the incidence and risk factors of treatment-related leukoencephalopathy (tLE) in a clinical setting. We retrospectively reviewed clinical and radiological findings of 126 patients with  (CNSL) treated with high-dose methotrexate with or without intrathecal methotrexate administration (IT MTX) and response-adapted WBRT. During the whole observation period with a median of 38.7 months, tLE was found in 33 patients, most of them asymptomatic, with the median time to development 3.0 months, and the cumulative incidence reaching 29.2% (95% confidence interval, 20.6-38.2%) two years post chemotherapy. By multivariable analysis, IT MTX was identified as the only one significant risk factor (hazard ratio, 4.50; P < 0.001), and the number of IT MTX was associated with the increased incidence and severity of tLE. These findings highlight the frequent neurological complications associated with CNS-directed therapy and confirm the neurotoxicity of IT MTX.

Spectrum of [18F]FDG PET/CT Findings in Primary Central Nervous System Lymphoma - A Pictorial Essay.

Primary central nervous system lymphoma (PCNSL) is a rare, aggressive variant of extranodal non-Hodgkin's lymphoma. Although gadolinium-enhanced magnetic resonance imaging remains the initial imaging modality of choice, a whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography-computed tomography is imperative to exclude systemic lymphomatous involvement. Furthermore, the metabolic parameter, maximum standardized uptake value (SUVmax) of the lesion, tumor-to-normal cerebral tissue SUVmax ratio, and FDG uptake patterns help in differentiating intracranial lymphomas from High-grade Glioblastoma Multiforme (HGM) and infectious lesions, and hence, consolidating the diagnosis. In this pictorial essay, we present a series of PCNSL cases, representing the different imaging characteristics and metabolic uptake patterns.

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.