Search Results (91)

Background: Intraventricular central nervous system (CNS) lymphoma is an atypical presentation of extranodal lymphoma, whether primary or secondary. The most commonly diagnosed subtype of lymphoma is diffuse large B-cell lymphoma (DLBCL). There is a documented relation of HIV, EBV and KSHV infections with lymphomagenesis. AIDS-related lymphomas (ARLs) are described as a defining illness of the acquired immunodeficiency syndrome (AIDS). This study presents a novel case and systematic review of clinical, radiographic and histopathological features of intraventricular lymphomas. Methods: We report on a 27-year-old woman with a left lateral ventricle DLBCL with surrounding edema treated with steroids. A systematic review of 147 additional cases (1977–2025) was conducted, analyzing patient demographics, tumor characteristics, clinical features, imaging, treatment, and outcomes. The tumor locations were divided into three groups depending on the extent of ventricular involvement. Descriptive statistics summarized findings. Findings: 147 cases (mean age, 54.2 years; range, 3–87; 63.3% male) were analyzed. Immunodeficiency in patients was unusual (6.1%). Fully intraventricular lesions were the most common presentation (52.4%), with systemic involvement solely in 10 cases (6.8%). The lesions were predominantly located in the lateral ventricles or fourth ventricles (46 times each), and bilateral involvement was noted 37 additional times. DLBCL was diagnosed in 101 cases (78.9%). Interpretation: Intraventricular involvement in central nervous system lymphoma poses a diagnostic and therapeutic challenge due to non-specific symptoms and atypical locations. Adding to the diagnostic difficulty of intraventricular masses in young patients, we wish to highlight that immunocompromised patients are a notably insignificant subgroup of patients in our study. Full article

Epstein–Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving chronic mycophenolate mofetil (MMF) therapy outside the transplant setting. The patient presented with progressive neurological deficits, and brain magnetic resonance imaging demonstrated multiple enhancing lesions. Stereotactic biopsy revealed diffuse large B-cell lymphoma of non–germinal center subtype with immunoblastic features and EBV-encoded RNA (EBER) positivity, confirming EBV-positive PCNSL. MMF was discontinued, and the patient was treated with rituximab and high-dose methotrexate, resulting in stable disease. This case highlights that prolonged MMF therapy may confer sufficient immunosuppression to permit EBV-driven lymphoproliferative disease even in non-transplant patients. Early recognition, withdrawal of immunosuppression, and initiation of methotrexate-based chemotherapy can lead to favorable outcomes. Full article

Primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which early management decisions frequently occur within neurosurgical workflows prior to oncologic treatment. In this retrospective single-center study, we aimed to explore whether early neurosurgical workflow characteristics are associated with survival outcomes in patients with PCNSL. Consecutive adult patients diagnosed with PCNSL between 2012 and 2022 were included, and the variables of interest comprised pre-biopsy corticosteroid exposure, the interval between diagnostic magnetic resonance imaging (MRI) and stereotactic biopsy, and the time from biopsy to initiation of high-dose methotrexate–based induction therapy. All patients were treated under a standardized hematology protocol to limit systemic treatment heterogeneity. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of diagnostic biopsy, and survival analyses were performed using Kaplan–Meier methods and log-rank testing. Twenty-nine patients met the inclusion criteria. Median OS and PFS were not reached in steroid-naïve patients, whereas pre-biopsy corticosteroid exposure was associated with consistently shorter survival trajectories, with a clear separation of the survival curves, despite conventional statistical significance not being reached. Similarly, median OS and PFS were not reached in patients undergoing biopsy within 7 days of MRI, and an MRI-to-biopsy interval exceeding 7 days demonstrated an unfavorable survival trajectory compared with earlier biopsy; biopsy-to-induction timing did not show a measurable association with early survival outcomes. Established prognostic stratification using Memorial Sloan–Kettering Cancer Center classes showed expected survival discrimination within the cohort, supporting internal validity. Given the limited sample size and retrospective design, all findings should be interpreted as exploratory associations rather than evidence of causality. These results suggest that early neurosurgical workflow characteristics, particularly empiric pre-biopsy corticosteroids avoidance and diagnostic delay minimization, may be associated with early survival trajectories in PCNSL and warrant further evaluation in larger prospective studies. Full article

Background: Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma characterized by a poor prognosis due to high relapse rates and a lack of standardized treatment. This study aimed to evaluate the impact of induction/consolidation therapy on long-term survival and to provide extended follow-up data. Methods: In this retrospective analysis, 140 immunocompetent patients with diffuse large B-cell PCNSL (DLBCL-PCNSL) treated at two centers between 2014 and 2024 were enrolled. Treatment efficacy was assessed based on baseline characteristics, therapeutic regimens, and treatment response. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and prognostic factors were identified using multivariate Cox proportional hazards regression models. Results: With a median follow-up of 5.3 years (range: 0.1–11.0 years), the 2- and 5-year PFS rates were 50.4% (95% CI: 42.1–60.2) and 34.1% (95% CI: 25.5–45.0), respectively, while the corresponding OS rates were 85.3% (95% CI: 79.4–91.6) and 60.8% (95% CI: 52.0–71.1). No survival plateau was observed. Among patients, 94% received methotrexate-based induction therapy: 94 received rituximab–methotrexate–temozolomide (R-MT) and 17 received MT alone, with 2-year PFS rates of 57.7% and 39.7%, respectively. Overall, 75% of patients achieved remission (CR/CRu/PR) after induction, and among these, 55% underwent consolidation therapy, predominantly autologous stem cell transplantation (ASCT, 90%) or whole-brain radiotherapy (10%). Patients receiving ASCT exhibited superior survival outcomes compared to those who did not. Conclusions: R-MT induction combined with ASCT consolidation is associated with improved survival in PCNSL, although relapse risk remains substantial. Outcomes remain poor in refractory subgroups, highlighting the need for novel therapeutic strategies. Full article

Background/Objectives: Relapsed and refractory (rr) primary large B-cell lymphoma of the central nervous system (PCNSL) has a dismal prognosis, and the standard of care is not established. The most common genetic imbalance includes the B-cell lymphoma 2 (BCL-2) locus. Methods: We planned a bi-centric phase Ib dose-escalation study with the chemotherapy-free combination of the BCL-2 inhibitor venetoclax and CD20 antibody obinutuzumab for rrPCNSL patients in Germany. The intended treatment consisted of 6 cycles of fixed-dose obinutuzumab at 1000 mg intravenously every 3 weeks, and an oral daily dose of 600, 800, or 1000 mg venetoclax, depending on the planned dosing group, followed by a 12-month venetoclax maintenance period. The primary endpoint was the pharmacokinetics of venetoclax and obinutuzumab in cerebrospinal fluid (CSF). Results: This study was prematurely terminated after registration of 5/15 (33%) patients in dosing group 1 (600 mg oral daily dose of venetoclax) between May 2020 and November 2021. The mean ratio of the concentration of venetoclax in CSF over peripheral blood was 0.55% (±0.28 standard deviation (SD)) and 0.25% (±0.23 SD) for obinutuzumab. Two of five patients achieved complete remission, and each one patient achieved partial remission and stable disease as best response. The median duration of response was 6.5 months (range 0.7–47). Conclusions: Venetoclax and obinutuzumab can penetrate into the central nervous system, but the CSF concentration did not correlate with the outcome. The combination is feasible, tolerable, and may lead to durable responses in selected rrPCNSL patients. Full article

Objectives: To determine the incidence of delayed methotrexate elimination (DME) and acute kidney injury (AKI) and their associations with clinical outcomes in patients receiving high-dose methotrexate (HDMTX) for cancer treatment. Methods: The HDMTX European Registry collected medical records data from 12 institutions in 5 European countries to investigate the clinical practice patterns of healthcare providers utilizing HDMTX for cancer treatment. Cancer types included were acute lymphoblastic leukemia (ALL), primary central nervous system lymphoma (PCNSL), non-Hodgkin lymphoma (NHL), osteosarcoma, and other CNS cancers. Primary endpoints were the incidence of DME and AKI; secondary endpoints were clinical outcomes, including hospital length of stay (LOS), delay in the subsequent course of treatment, methotrexate dose reduction, and omission of next course of treatment. Associations between the primary and secondary endpoints were analyzed with Chi-square and Wilcoxon rank-sum tests. Results: Among the 2501 total HDMTX courses analyzed, DME occurred in 302 courses (12.1%), and AKI in 384 courses (15.4%). DME incidence was highest in courses for PCNSL (18.2%) and NHL (17.2%); AKI incidence was highest in ALL courses (21.0%). Incidence of DME and AKI varied by age and methotrexate infusion duration among the different cancer types. Occurrence of DME was associated with longer delays prior to the next course of treatment, longer hospital LOS, and more frequent methotrexate dose reductions and dose omissions. Conclusions: While HDMTX is a very effective and safe treatment, administration of efficacious doses of methotrexate can lead to AKI and DME, and no single or combination of patient or treatment factors was found to reliably predict their occurrence. Thus, diligent monitoring of methotrexate levels is imperative for early detection and prompt management of nephrotoxicity in all settings where HDMTX treatment is administered. Full article

Background/Objectives: Short induction followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) is effective in newly diagnosed elderly patients with primary central nervous system lymphoma (PCNSL) but associated with significant toxicity. Geriatric assessments (GAs) may help to predict treatment risk and prognosis, yet no standardized GAs exist for PCNSL. Our aim was to evaluate the impact of GA on HCT-ASCT eligibility and survival. Methods: We analyzed 65 patients > 65 years treated in the MARiTA and MARTA studies. Treatment comprised 2 cycles of rituximab, HD-MTX and cytarabine followed by HCT-ASCT. GAs at diagnosis were analyzed for progression-free survival (PFS), overall survival (OS) and premature end of treatment (pEOT). Results: After median follow-up of 43 months, 12-month PFS/OS were 69.2% (95% CI 56.5–78.9%)/70.8% (58.1–80.2%) from diagnosis and 80.4% (66.6–88.9%)/84.3% (71.1–91.8%) from time of HCT-ASCT. ECOG PS ≥ 2, Lachs geriatric screening (Lachs) ≥30% and Cumulative Illness Rating Scale-Geriatric (CIRS-G) ≥6, ≥7 and ≥8, respectively, were significantly associated with pEOT in univariate analysis (UVA). In multivariate analysis (MVA), CIRS-G remained significant. A composite EBL score (ECOG PS ≥ 2, Barthel Index of Activities of Daily Living (Barthel) < 20, Lachs ≥ 30%) ≤1 predicted successful completion of HCT-ASCT in >90% of patients. ECOG PS ≥ 2 and Barthel < 20 were associated with decreased PFS and OS in UVA; ECOG PS ≥ 2 remained significant in MVA. Conclusions: This is the first study to link GA with treatment feasibility in elderly PCNSL patients undergoing intensive therapy. Our results will be validated in the PRIMA-CNS trial (EudraCT 2020-001181-10). Full article

Background/Objectives: Primary central nervous system lymphoma (PCNSL) has a markedly high proliferation rate, making early diagnosis and prompt therapeutic intervention essential. To accelerate diagnosis, our institution adopted flow cytometry (FCM) in conjunction with conventional histopathology, and this study therefore evaluated the diagnostic performance of FCM for PCNSL. Methods: We retrospectively analyzed 67 consecutive patients with suspected PCNSL who underwent intraoperative FCM between 2010 and 2023 based on preoperative imaging. B-cell clonality was defined as ≥20% CD19/CD20-positive cells with a κ/λ ratio of >3.0 or <0.5. Results: Using histopathology, we confirmed the presence of PCNSL in 42 patients, all diagnosed as having diffuse large B-cell lymphoma. Six cases (14.3%) were discordant (FCM-D). The sensitivity, specificity, and positive predictive value of FCM were 85.7%, 100%, and 100%, respectively. T-cell markers were significantly elevated in FCM-D cases (p < 0.01), although these were pathologically diagnosed as diffuse large B-cell lymphoma based on histology and immunohistochemistry. Conclusions: FCM yields reliable diagnostic information within hours of tissue collection and supports early therapeutic decisions in PCNSL. Discordant results may reflect reactive T-cell infiltration. This is the first study to present detailed subset analyses in PCNSL using FCM in correlation with pathology, underscoring its utility as a rapid diagnostic tool. Full article

Objectives: The potential use of electron density (ED) and effective atomic number (Zeff) derived from dual-energy computed tomography (DECT) as novel quantitative imaging biomarkers for differentiating malignant brain tumors was investigated. Methods: Data pertaining to 136 patients with a pathological diagnosis of brain metastasis (BM), glioblastoma, and primary central nervous system lymphoma (PCNSL) were retrospectively reviewed. The 10th percentile, mean and 90th percentile values of conventional 120-kVp CT value (CTconv), ED, Zeff, and relative apparent diffusion coefficient derived from diffusion-weighted magnetic resonance imaging (rADC: ADC of lesion divided by ADC of normal-appearing white matter) within the contrast-enhanced tumor region were compared across the three groups. Furthermore, machine learning (ML)-based diagnostic models were developed to maximize diagnostic performance for each tumor classification using the indices of DECT parameters and rADC. Machine learning models were developed using the AutoGluon-Tabular framework with rigorous patient-level data splitting into training (60%), validation (20%), and independent test sets (20%). Results: The 10th percentile of Zeff was significantly higher in glioblastomas than in BMs (p = 0.02), and it was the only index with a significant difference between BMs and glioblastomas. In the comparisons including PCNSLs, all indices of CTconv, Zeff, and rADC exhibited significant differences (p < 0.001–0.02). DECT-based ML models exhibited high area under the receiver operating characteristic curves (AUC) for all pairwise differentiations (BMs vs. Glioblastomas: AUC = 0.83; BMs vs. PCNSLs: AUC = 0.91; Glioblastomas vs. PCNSLs: AUC = 0.82). Combined models of DECT and rADC demonstrated excellent diagnostic performance between BMs and PCNSLs (AUC = 1) and between Glioblastomas and PCNSLs (AUC = 0.93). Conclusion: This study suggested the potential of DECT-derived ED and Zeff as novel quantitative imaging biomarkers for differentiating malignant brain tumors. Full article

We present the case of a patient with primary CNS lymphoma (PCNSL), with MYD88 and CD79B gene variants, who was unable to complete standard induction and consolidation treatment due to toxicity and co-morbidities after three cycles of MATRix. Although he had responded to truncated induction, acalabrutinib, the BTK inhibitor, was used in an attempt to consolidate and maintain his response. He has an ongoing remission at 18 months of follow-up. Following the case presentation, we provide a review of PCNSL, the evolution of therapy, and how BTK inhibitors are now emerging treatments incorporated into the salvage of relapsed and refractory disease and into first-line treatment in some clinical trials. This is the first reported case in the literature of acalabrutinib use for consolidation and maintenance of PCNSL. We hope this can support clinical trial design for BTKi use in this setting in the future. Full article

Background: Primary central nervous lymphoma (PCNSL) is a rare, aggressive, non-Hodgkin’s lymphoma. Outcomes are poor with standard induction of high-dose methotrexate (HD-MTX)-based regimens and consolidation. We present retrospective data from the Georgia Cancer Center. Methods: A single retrospective chart review was conducted on all PCNSL patients from 2013 to 2023 to assess for various factors influencing care. Results: Of a total of 38 PCNSL patients, 6 died and 2 were lost to follow-up prior to therapy initiation, leading to a total of 30 patients for analysis. The median age was 62.3 (21–82 years). One patient had HIV/AIDS. Two patients were on immunosuppression for either kidney transplant or multiple sclerosis (MS). The HIV and MS cases were Epstein-Barr Virus (EBV)-positive. Completion of ≥six cycles of induction was predictive of response. Conclusions: PCNSL remains an area of high unmet need. Recent studies have shown that HD-MTX-based therapy and autologous stem cell transplantation afterwards leads to improved outcomes regardless of age; however, non-relapse mortality is important to consider. Our data from a primarily elderly and sub-rural cohort reiterate the efficacy of combination chemoimmunotherapy and impact of induction cycle number on response, regardless of age. A multidisciplinary approach and targeted agent maintenance should be considered to improve outcomes in the elderly. Full article

Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma confined to the central nervous system. The cancer biology of PCNSL remains incomplete and is often associated with genetic aberrations with abnormal signaling pathways, cell differentiation, regulation of epigenetic modification, and the tumor microenvironment. Stereotactic brain biopsy remains the gold standard for the diagnosis of PCNSL. For patients ill-suited for biopsy, MYD88 and IL-10 may be important biomarkers to diagnose PCNSL. High-dose methotrexate-based polychemotherapy is currently the standard induction treatment for PCNSL, followed by consolidation treatments including autologous stem cell transplant and whole-brain radiotherapy. Some studies suggest that low-dose lenalidomide is recommended as a maintenance therapy for PCNSL. Currently, relapse rates of PCNSL range from 25 to 50% with poor prognosis. Insight research is necessary to identify novel targeted treatments to improve outcomes in relapsed/refractory disease, such as immunomodulatory drugs, immune checkpoint inhibitors, signaling pathway inhibitors, and chimeric antigen receptor T-cell therapy. Full article

To deliver the most effective cancer treatment, clinicians require rapid and accurate diagnoses that delineate tumor type, stage, and prognosis. Consequently, minimizing the need for repetitive and invasive procedures like biopsies and myelograms, along with their associated risks, is a critical challenge. Non-invasive monitoring offers a promising avenue for tumor detection, screening, and prognostication. While the identification of oncogenes and biomarkers from circulating tumor cells or tissue biopsies is currently standard practice for cancer diagnosis and classification, accumulating evidence underscores the significant role of epigenetics in regulating stem cell fate, including proliferation, self-renewal, and malignant transformation. This highlights the importance of analyzing the methylome, exosomes, and circulating RNA for detecting cellular transformation. The development of diagnostic assays that integrate liquid biopsies with epigenetic analysis holds immense potential for revolutionizing tumor management by enabling rapid, non-invasive diagnosis, real-time monitoring, and personalized treatment decisions. This review covers current studies exploring the use of epigenetic regulation, specifically the methylome and circulating RNA, as diagnostic tools derived from liquid biopsies. This approach shows promise in facilitating the differentiation between primary central nervous system lymphoma and other central nervous system tumors and may enable the detection and monitoring of acute myeloid/lymphoid leukemia. We also discuss the current limitations hindering the rapid clinical translation of these technologies. Full article

Background: The gold standard for diagnosing primary central nervous system lymphoma (PCNSL) is brain biopsy, an invasive procedure with significant risks. The role of cerebrospinal fluid (CSF) examination, limited to cytology and flow cytometry in current practice, is acknowledged as a less invasive diagnostic method. We aimed to summarize available data concerning the efficacy and actual use of current standard CSF diagnostics in the diagnosis of PCNSL. Methods: A systematic review and meta-analysis of 144 studies (n = 9493 patients) was conducted, assessing detection rates of cytology and flow cytometry and the proportion of diagnoses based on CSF analysis. The QUADAS-2 tool was used to evaluate study quality and bias. Results: Meta-analysis showed an 18% pooled detection rate for positive CSF results, with 17% for cytology and 20% for flow cytometry. Only 8% of diagnoses were made using CSF analysis. Most studies had a high risk of bias. Conclusions: Despite its established role in guidelines, CSF analysis remains underutilized for diagnosing PCNSL, with room to improve its clinical impact. Novel techniques, such as chemokines and circulating tumor DNA (cfDNA) analysis, hold promise to unlock the untapped potential of CSF diagnostics, offering significant advancements in non-invasive PCNSL diagnosis. Full article

Brain metastases (BMs) are the most common intracranial tumors in adults. Their heterogeneity, potential multifocality, and complex biomolecular behavior pose significant diagnostic and therapeutic challenges. Artificial intelligence (AI) has the potential to revolutionize BM diagnosis by facilitating early lesion detection, precise imaging segmentation, and non-invasive molecular characterization. Machine learning (ML) and deep learning (DL) models have shown promising results in differentiating BMs from other intracranial tumors with similar imaging characteristics—such as gliomas and primary central nervous system lymphomas (PCNSLs)—and predicting tumor features (e.g., genetic mutations) that can guide individualized and targeted therapies. Intraoperatively, AI-driven systems can enable optimal tumor resection by integrating functional brain maps into preoperative imaging, thus facilitating the identification and safeguarding of eloquent brain regions through augmented reality (AR)-assisted neuronavigation. Even postoperatively, AI can be instrumental for radiotherapy planning personalization through the optimization of dose distribution, maximizing disease control while minimizing adjacent healthy tissue damage. Applications in systemic chemo- and immunotherapy include predictive insights into treatment responses; AI can analyze genomic and radiomic features to facilitate the selection of the most suitable, patient-specific treatment regimen, especially for those whose disease demonstrates specific genetic profiles such as epidermal growth factor receptor mutations (e.g., EGFR, HER2). Moreover, AI-based prognostic models can significantly ameliorate survival and recurrence risk prediction, further contributing to follow-up strategy personalization. Despite these advancements and the promising landscape, multiple challenges—including data availability and variability, decision-making interpretability, and ethical, legal, and regulatory concerns—limit the broader implementation of AI into the everyday clinical management of BMs. Future endeavors should thus prioritize the development of generalized AI models, the combination of large and diverse datasets, and the integration of clinical and molecular data into imaging, in an effort to maximally enhance the clinical application of AI in BM care and optimize patient outcomes. Full article