Central Nervous System Lymphoma Research Articles

Efficacy and safety of first-line high-dose cytarabine in patients with primary CNS lymphoma ineligible for high-dose methotrexate: a case series

Abstract Introduction Despite recent significant advances, the treatment of elderly patients with primary central nervous system lymphoma (PCNSL) is still challenging due to comorbidities, poor baseline performance status (PS), and drug toxicities. There are proposals to use high-dose cytarabine (HD-araC) in these patients. Results Our retrospective study aimed to assess the efficacy and toxicity of HD-araC as an upfront treatment for patients with PCNSL who are ineligible for high-dose methotrexate (HD-MTX). Methods We identified 12 consecutive patients with newly diagnosed PCNSL (out of a total of 68) who received first-line treatment with HD-araC, with or without rituximab (R). Most of them had poor PS and relevant comorbidities. Six patients received this treatment upfront, while the other six received it after discontinuing HD-MTX-(based) therapy. Treatment with HD-araC resulted in poor outcome, limited response, and severe hematological and infectious complications. Patients who had previously received at least one cycle of HD-MTX appeared to have slightly better outcomes, highlighting the importance of HD-MTX in the treatment of PCNSL. Conclusion Our case series showed limited efficacy and substantial toxicity of (R)-HD-araC in patients with PCNSL ineligible for HD-MTX. This treatment should be omitted in elderly/frail patients to avoid further compromising their quality of life.

MRI-based Radiomics Virtual Biopsy for BCL6 in Primary Central Nervous System Lymphoma

AimTo establish machine learning model based on radiomic signature for predicting B-cell lymphoma 6 (BCL-6) rearrangement in primary central nervous system lymphoma (PCNSL). Materials and MethodsRetrospective study on 102 PCNSL patients (31 with BCL-6 rearrangement positive, 71 with BCL-6 rearrangement negative) were randomly divided into the training and validation set at a ratio of 7:3. Radiomics models based on contrast-enhanced T1-weighted imaging (CE-T1WI) and fluid-attenuated inversion recovery (FLAIR) in different regions including VOItumor core and VOIperitumoral edema. Radiomics features were extracted and selected using LASSO regression, and radiomics score (rad-score) were calculated using the weighted coefficients. Four machine learning models (logistic regression, random forest, support vector machine, K-nearest neighbors) were developed and evaluated based rad-score. The optimal radiomics model was integrated into the clinical or radiological factors to construct a predictive model through logistic regression analysis. A nomogram was constructed based on independent significant features for individualized prediction. ResultsAll rad-scores based on CE-T1WI and FLAIR sequences were significantly associated with BCL6 rearrangement (p<0.05) in univariate regression analysis. LR machine learning model performed best with AUCs of 0.935 (training) and 0.923 (validation). Rad-scores from CE-T1WI tumor core and peritumoral edema were independent significant predictors. ConclusionRadiomics signature based on CE-T1WI and FLAIR sequences have significant value in distinguishing BCL6 rearrangement. The CE-T1WI radiomics model based on VOItumor core and VOIperitumoral edema are robust markers for identifying BCL6 rearrangement.

Distinguishing clinical and imaging characteristics of primary central nervous system lymphoma from high-grade glioma and metastatic brain tumors.

The purpose of this retrospective analysis was to evaluate the clinical presentations, radiological characteristics, patient outcomes, and therapeutic approaches among individuals diagnosed with primary central nervous system lymphoma (PCNSL), high-grade glioma (HGG), and metastatic brain tumors (METS). We assembled a cohort of brain tumor patients from two medical centers, with two oncologists independently reviewing their clinical profiles. A retrospective examination of 87 PCNSL, 87 HGG, and 71 METS cases was performed to assess the aforementioned parameters. Notable variations were identified in the incidence of epileptic seizures and cognitive impairments between PCNSL and METS patients. Cerebral hemisphere involvement was predominantly observed in HGG and METS cases. PCNSL cases exhibited a higher likelihood of multiple lesions, whereas HGG showed a greater tendency for recurrence. The median survival times were established at 24.3months for PCNSL, 44.5months for HGG, and 27.1months for METS patients. In PCNSL cases, the number of lesions was identified as a significant predictor of mortality (P = 0.008). Our findings highlight the importance of clinical and imaging features in diagnosing PCNSL, which may present distinct features compared to HGG and METS.

CAR T-cell Therapy for Central Nervous System Lymphoma.

While anti-CD19 CAR T-cell therapy represents a major advance in systemic diffuse large B-cell lymphomas, central nervous system (CNS) lymphomas have been excluded from pivotal trials because of the fear of neurotoxicity. The purpose of this review was to assess the efficacy and tolerance of CAR T-cells in CNS lymphomas based on recently published studies. All the studies on CAR T-cell therapy for both primary and secondary CNS lymphomas reported high response rates (complete response rates ranging from 32 to 67%) in highly pre-treated patients. One-year PFS reached 40 to 60% in several studies. Neurotoxicity occurred in 36 to 68% of patients, including grade 3-4 neurotoxicity in 4.5 to 29% of patients. CAR T-cell therapy appears to be a very promising treatment in CNS lymphomas, with efficacy results close to those observed in systemic lymphomas. The toxicity profile, notably regarding neurotoxicity, is reassuring and should not prevent the development of CAR T-cells in the disease.

High-Dose Chemotherapy and Autologous or Allogeneic Transplantation in Aggressive B-Cell Lymphoma-Is There Still a Role?

Novel therapies such as CAR-T, BTK inhibitors and PD-1 inhibitors have changed the management of aggressive B-cell lymphomas. Nonetheless, these novel therapies have their own risk of late toxicities including second malignancies. They also create a subgroup of patients with relapse, treatment failure, or indefinite maintenance. We discuss the current role of autologous and allogeneic stem cell transplantation in this context. In patients with recurrent diffuse large B-cell lymphoma, CAR-T cell treatment has largely replaced autologous transplant. Autologous transplant should be considered in patients with late relapses and in selected patients with T-cell-rich B-cell lymphoma, where CAR-T cell therapy may be less effective. It also remains the treatment of choice for consolidation of patients with primary CNS lymphoma. In mantle cell lymphoma, intensive chemotherapy combined with BTK inhibitors and rituximab results in excellent outcomes, and the role of autologous transplantation is declining. In Hodgkin's lymphoma, autologous transplant consolidation remains the standard of care for patients who failed initial chemotherapy. Allogeneic transplantation has lower relapse rates but more complications and higher non-relapse mortality than autologous transplantation. It is usually reserved for patients who fail autologous transplantation or in whom autologous stem cells cannot be collected. It may also have an important role in patients who fail CAR-T therapies. The increasing complexity of care and evolving sequencing of therapies for patients with aggressive B-cell lymphomas only emphasizes the importance of appropriate patient selection and optimal timing of stem cell transplantation.

Surgical Considerations in Treating Central Nervous System Lymphomas: A Case Series of 11 Patients

In this retrospective unicentric study, we analyzed the medical records of 11 patients who were surgically treated for CNS lymphoma, both primary and secondary, between 2009 and 2024. Given the rarity of CNS lymphomas and their diverse signs and symptoms based on tumoral location, our aim was to describe key aspects, such as clinical presentations and surgical management. A possible relationship between obesity and CNS lymphoma progression was investigated through an analysis of previous study findings. The literature suggests a wide spectrum of manifestations, from nausea and headaches to loss of equilibrium and speech impairment. A predominance of unsystematized balance disorders and epileptic seizures were affirmed. Notably, as emerged from our study, aphasia was a particularly interesting neurological symptom due to its rarity in the clinical features of CNSL. Other significant factors, such as tumor localization and perioperative phases, were thoroughly investigated, with the latter highlighted by an illustrative case report. Additionally, a literature review was included, comprising nine recent retrospective studies on the efficacy of surgical resection for patients diagnosed with PCNSL.

Managing Primary Central Nervous System Lymphoma in Immunocompetent Elderly Patients

Managing Primary Central Nervous System Lymphoma in Immunocompetent Elderly Patients

Primary central nervous system lymphoma: a series report and literature review

ObjectiveThis study aims to analyze the clinical features, Radiological findings and diagnostic characteristics (tissue biopsy, flow cytometry and cerebrospinal fluid cytology) of primary central nervous system lymphoma (PCNSL). To improve the diagnosis of the disease.MethodsA total of 19 patients with primary central nervous system lymphoma admitted to the Second Hospital of Hebei Medical University from 2014 to 2023 were selected. The clinical data of the patients were retrospectively analyzed. Combined with the relevant literature, the clinical characteristics of PCNSL patients were analyzed to assist the diagnosis.ResultMost of the patients were middle-aged and elderly patients (65 years old), and the main clinical manifestations showed no obvious specificity, including headache, dizziness and limb weakness. Radiological findings showed that common site of currence were located in the brain parenchyma. The PCNSL subtype of 19 patients was all diffuse large B cell subtype by cytology, flow cytometry or histopathology. Six cases were diagnosed by biopsy pathology and 11 cases were diagnosed by flow cytometry of cerebrospinal fluid. In all patients diagnosed with PCNSL by clinical cytology (CSF cytology and flow cytometry), abnormal cells were found on CSF examination.ConclusionThe pathological type of primary central nervous system lymphoma was diffuse large B-cell subtype, with diverse clinical manifestations and multiple. Both tissue directed biopsy and flow cytometry could effectively assist clinical diagnosis. Early and timely diagnosis and intervention are of great significance for delaying the disease process and reducing the economic burden of patients and families.

Efficacy and Safety of Ibrutinib as Monotherapy or Combination Therapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL): A Systematic Review and Meta-analysis.

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease group. Ibrutinib's monotherapy or combination therapy is effective in relapsed/refractory (R/R) DLBCL. However, the treatment response in R/R DLBCL varies from 15% to 90% with different regimens, and the tolerance remains controversial. The efficacy and safety of ibrutinib monotherapy or combination therapy in patients with R/R DLBCL remain uncertain. The PubMed, CBM, MEDLINE, Cochrane Library, and Embase databases were searched from their inception to July 2021. The total complete remission rate (CRR) and overall response rate in R/R DLBCL patients treated with ibrutinib were 26% and 49%, respectively. The CRR of ibrutinib combination therapy was significantly higher than the ibrutinib monotherapy (45% vs. 19%). Moreover, the CRR of patients was 40% in double expressing lymphoma, 35% in central nervous system lymphoma, and 33% in nongerminal center B-cell-like (non-GCB) DLBCL, which was higher than the 8% in those with the GCB subtype. The pooled median PFS and overall survival were 5.57 and 10.17 months, respectively. GCB-DLBCL had the worst overall survival (5.1 months). Nevertheless, we found that combination regimens had no survival advantage compared with monotherapy (P > 0.05), indicating that combination therapy was only a transitional treatment and bridge for chimeric antigen receptor T cells or other treatments. Moreover, 12% of patients on ibrutinib combination therapy had ≥grade 3 adverse events compared with 9% on ibrutinib monotherapy. Ibrutinib monotherapy or combination therapy was safe and effective in treating R/R DLBCL with tolerable adverse reactions.

RE-VISITING BIOPSIES FOR SUSPECTED CNS LYMPHOMAS: TO BIOPSY OR NOT TO BIOPSY?

Abstract AIMS It is a common practice to get a histological diagnosis before treatment of suspected CNS (central nervous system) lymphoma. Should CNS lesions be routinely biopsied in patients with background systemic lymphoma? METHOD A 10-year retrospective review of biopsy-proven CNS lymphoma was conducted. Data was analyzed using SPSS for Windows, version 25 (SPSS, Inc., Chicago, Illinois, USA), and a p-value &amp;lt; 0.05 was considered significant for the appropriate test statistic. RESULTS Patients with background systemic lymphoma whose brain MRI appearances were in favour of lymphoma after MDT discussion all had histologically-proven lymphoma after brain biopsy. Pre-biopsy MDT diagnosis was congruent with post-biopsy histology in 87.6% of cranial lesions (p-value 0.003) and 40% of spinal lymphomas (p-value 0.002). Secondary CNS lymphoma was seen in 21.2%. Stereotactic brain biopsy was the most common biopsy technique for cranial lesions (79.8%). Histology was Diffuse B Cell Lymphoma in 93% of cases. The mean Ki67 percentage for cranial lymphomas was higher than that of spine (p-value 0.028) The complication rate for cranial biopsy was 8.9%. Transient motor deficits (4.4%) and post-operative haematoma (2.2%) were the most common. The 24-hour post-brain biopsy mortality rate was 1.1%, while overall 30-day post-op mortality rate was 4.4%. The mean percentage of Ki67 was higher among patients who had complications (p-value 0.001). CONCLUSION In a setting of properly constituted neurooncology MDT, a sub-set of patients with suspected brain lymphoma and background systemic lymphoma might not require brain biopsy. KEY WORDS Lymphoma, Brain, Spine, Biopsy, Complication

THE UTILITY OF MULTIPARAMETRIC MRI IN REDUCING DIAGNOSTIC UNCERTAINTY FOR PRIMARY CNS LYMPHOMA

Abstract AIMS A key limitation in the early treatment initiation in primary central nervous system lymphoma (PCNSL) is the diagnostic delay caused by lack of recognition of a lesion as a possible lymphoma, steroid initiation, and lesion involution, often resulting in inconclusive biopsy. We highlight the importance of multiparametric MRI (MPMRI), which incorporates diffusion weighted imaging (DWI), dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI) and proton magnetic resonance spectroscopy (1H-MRS) in addition to standard MRI sequences in resolving diagnostic uncertainty for PCNSL. METHOD We present a consecutive series of 10 patients at our centre with histology-proven PCNSL (specifically, diffuse large B-cell lymphoma of the CNS) who underwent multiparametric MRI. We retrospectively analyse the qualitative and semi-quantitative parameters and assess their radiological concordance for this diagnosis. RESULTS We note overall low apparent diffusion coefficient on DWI (mean ADCmin of 0.74), high percentage signal recovery on perfusion weighted imaging (mean 170%), a high choline-creatine ratio and a high-grade lipid peak on MRS giving a “twin-tower” appearance. Nine of ten patients had MRMRI findings concordant for PCNSL, defined as at least 3 of 4 parameters being consistent for PCNSL. CONCLUSION We propose that concordance between these imaging multiparametric modalities could be used as a radiological predictor of PCNSL, reducing diagnostic delays, providing a more accurate biopsy target, and resulting in quicker treatment initiation.

Diagnostic Value of sLR11 and sIL-2R in the Cerebrospinal Fluid for Malignant Central Nervous System Lymphoma.

Objective We previously reported that patients with acute leukemia and malignant lymphoma (ML) demonstrated significantly increased serum soluble LR11 (sLR11) levels compared to normal controls. Accurately diagnosing ML of the central nervous system (CNS ML) using cytology is frequently difficult. Therefore, we evaluated the use of cerebrospinal fluid (CSF) sLR11 and soluble interleukin-2 receptor (sIL-2R) as diagnostic and treatment response markers for CNS ML. Methods We retrospectively evaluated the CSF results for CNS ML using clinical data at our institution, and then analyzed the usefulness of sLR11 and sIL-2R in CSF for both the diagnosis and as surrogate markers that reflect the therapeutic effect. Patients We enrolled patients with CNS ML who received intrathecal anticancer drugs between 2017 and 2023. We analyzed the sLR11 and sIL-2R levels in CSF and cytological malignant grades. We studied 22 patients, including 17 with central nervous system (CNS) clinical conditions and five who received prevention treatment. Results The CSF sLR11 levels were significantly and positively correlated with CSF sIL-2R levels. The CSF sLR11 and sIL-2R levels in patients with CNS ML were significantly higher than those in the prevention group. A receiver operating characteristic (ROC) curve analysis showed the cut-off value of sLR11 for CNS invasion to be 21.7 ng/mL. Moreover, the chemotherapy-responder group demonstrated significantly decreased CSF sLR11 and sIL-2R levels after treatment. Conclusion CSF sLR11 and sIL-2R of CSF were found to be useful biomarkers for the diagnostic and treatment response evaluation in patients with CNS ML.

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

Biological Findings and Clinical Outcomes in Patients Treated With R-CHOP Plus High-Dose Methotrexate as First-Line Therapy in Large B-Cell Lymphoma With Testis Involvement.

Primary testicular lymphoma (PTL) is a rare occurrence of diffuse large B-cell lymphoma (DLBCL) that accounts for 1%-2% of all cases. Nodal DLBCL with testis involvement (DLBCL-T) and PTL are associated with poor prognosis, with high incidence of central nervous system relapse. Fifteen patients (median age 60 years) with PTL (n = 5) or DLBCL-T (n = 10) received high-dose methotrexate + R-CHOP. Overall, complete response (CR) rate was 73% and overall response rate 86%. With a 3.9-year median follow-up, 100% of patients with PTL had CR and none relapsed. On the contrary, 55% of DLBCL-T patients achieved CR among which only one was still in remission at the end of follow-up. Molecular parallels between PTL and Primary CNS Lymphoma (PCNSL) suggest shared origins, urging further research for tailored treatments and enhanced understanding of these lymphomas' biology.

MRI-Based Machine Learning for Prediction of Clinical Outcomes in Primary Central Nervous System Lymphoma.

A portion of individuals diagnosed with primary central nervous system lymphomas (PCNSL) may experience early relapse or refractory (R/R) disease following treatment. This research explored the potential of MRI-based radiomics in forecasting R/R cases in PCNSL. Forty-six patients with pathologically confirmed PCNSL diagnosed between January 2008 and December 2020 were included in this study. Only patients who underwent pretreatment brain MRIs and complete postoperative follow-up MRIs were included. Pretreatment contrast-enhanced T1WI, T2WI, and T2 FLAIR imaging were analyzed. A total of 107 radiomic features, including 14 shape-based, 18 first-order statistical, and 75 texture features, were extracted from each sequence. Predictive models were then built using five different machine learning algorithms to predict R/R in PCNSL. Of the included 46 PCNSL patients, 20 (20/46, 43.5%) patients were found to have R/R. In the R/R group, the median scores in predictive models such as support vector machine, k-nearest neighbors, linear discriminant analysis, naïve Bayes, and decision trees were significantly higher, while the apparent diffusion coefficient values were notably lower compared to those without R/R (p < 0.05). The support vector machine model exhibited the highest performance, achieving an overall prediction accuracy of 83%, a precision rate of 80%, and an AUC of 0.78. Additionally, when analyzing tumor progression, patients with elevated support vector machine and naïve Bayes scores demonstrated a significantly reduced progression-free survival (p < 0.05). These findings suggest that preoperative MRI-based radiomics may provide critical insights for treatment strategies in PCNSL.

Novel Therapies for Primary Central Nervous System Lymphomas.

Primary Central Nervous System Lymphoma (PCNSL) is an aggressive form of lymphoma that can involve the brain, spinal cord, leptomeninges and eyes. PCNSL prognosis continues to be poor, with 5-year survival rates of 30-40%. Therapeutic options are especially limited for relapsed/refractory (r/r) PCNSL. In recent years, studies shed light on the pathogenesis and oncogenic pathways driving PCNSL, leading to the development of novel therapeutics. In this review, we discuss the evidence supporting these novel agents and present ongoing clinical studies. Key oncogenic drivers of PCNSL include activation of the NFkB pathway, cell cycle dysregulation, somatic hypermutation and immune evasion, leading to the investigation of targeted therapeutics and immunotherapeutics to inhibit these pathways. Such approaches include BTK inhibitors, mTOR/PI3K inhibitors, immunomodulatory agents (IMIDs), immune checkpoint inhibitors and CD19-based CAR T-cells. The therapeutic repertoire for PCNSL is rapidly evolving, and a multi-modality approach including intensive chemotherapy regimens and novel therapies will likely be utilized in the future.

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.

Vitreoretinal lymphoma: the importance of cerebral spinal fluid evaluation at initial diagnosis

Background/aimsTo determine if patients with vitreoretinal lymphoma (VRL) and concomitant central nervous system lymphoma (CNSL) may present without brain MRI findings, but possess cerebrospinal fluid (CSF) suspicious for lymphoma.MethodsThis was...

Differentiating between Lymphoma and Metastasis Presenting as Solid Cerebellar Mass Lacking Necrosis

Objectives: This study aimed to identify radiologic features that differentiate lymphoma from metastasis manifesting as a solid enhancing mass lacking necrosis in the cerebellum. Methods: Pathologically confirmed 24 primary central nervous system lymphoma (PCNSL) and 32 metastasis patients with solid enhancing cerebellar masses without necrotic or hemorrhagic components were retrospectively analyzed. We evaluated the imaging characteristics using contrast-enhanced magnetic resonance imaging (MRI). The serrate sign was defined as a tumor spreading along white matter with branch-like enhancement or outward spikes. Results: The serrate sign was exclusively identified in the PCNSL group, showing a significant difference compared to the metastasis group (75.0% vs. 0%, p &lt; 0.001). Homogeneous enhancement occurred more frequently in PCNSL than in metastasis (91.7% vs. 21.9%, p &lt; 0.001). Conversely, bulging contour (62.5% vs. 4.2%, p &lt; 0.001) and surface involvement (71.9% vs. 29.2%, p = 0.003) were more prevalent in metastasis than PCNSL. For predicting PCNSL, the serrate sign demonstrated 75.0% sensitivity, 100% specificity, 100% positive predictive value, 84.2% negative predictive value, and 89.3% accuracy. Conclusions: This study found that the serrate sign and homogeneous enhancement are reliable MRI features for differentiating cerebellar PCNSL from metastasis, whereas a bulging contour and surface involvement suggest metastasis. The serrate sign demonstrated diagnostic significance in differentiating PCNSL from metastasis.

Liquid biopsy for CNS lymphoma: CSF exosomes and CSF exosomal miR-15a, miR-21, miR-155, miR-210, and miR-19b are promising biomarkers for diagnosis.

Central nervous system lymphoma (CNSL) is a devastating disease with a poor prognosis. Early diagnosis, monitoring of the treatment response, and outcome prediction carry the utmost importance in the management of patients with CNSL. Surgical biopsy is the gold standard for tissue diagnosis, however, this procedure has potential complications. Therefore, there is a need for a method that provides information about diagnosis and patient monitoring to avoid surgical risks. The study aimed to investigate potential diagnostic biomarkers for patients with CNSL. Patients with secondary CNSL were included in this study. Serum and cerebrospinal fluid (CSF) samples were collected before treatment and after completion of the treatment. Cell-free DNA (cfDNA), exosomes, free and exosomal microRNA (miR)-15a, miR-21, miR-155, miR-210, and miR-19b in both serum and CSF were examined, and they were compared with the controls. Also, their levels before and after treatment were compared. Nine patients with the diagnosis of secondary CNSL were reviewed. cfDNA, miR-15a, and miR-155 in serum, and exosome in CSF were found to be significantly higher in CNSL patients compared to the controls. Exosomal miR-15a, miR-21, miR-155, miR-210, and miR-19b in CSF were found to be significantly higher in CNSL patients compared to controls, whereas their levels in serum were not significantly high. Our findings suggested that exosomes and exosomal miR-15a, miR-21, miR-155, miR-210 and miR-19b in CSF would be promising biomarkers for the diagnosis of patients with CNSL. Further studies are needed to confirm our findings.