Central Nervous System Malignant Lymphoma Research Articles

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.

BIOM-40. COMPARATIVE STUDY OF INFLAMMATORY MARKERS IN THE CEREBROSPINAL FLUID OF PATIENTS WITH GLIOMA AND CENTRAL NERVOUS SYSTEM MALIGNANT LYMPHOMA

Abstract INTRODUCTION Cytokines in the cerebrospinal fluid (CSF) are useful as markers for primary central nervous system malignant lymphoma (PCBSL). However, there are few reports of CSF markers in glioma. We analyzed and examined glioma and PCNSL CSF inflammation-related mediators. MATERIALS AND METHODS The patients with glioma and PCNSL who were operated on at Kobe University between 2006 and 2017 and whose histology was diagnosed, and whose CSF was stored at -80 °C before treatment. Using Bio-Plex Pro Human Inflammation Assays (Bio-Rad Laboratories, Inc.), 37 types of inflammation-related molecules such as TNF superfamilies, interferonss, and Interleukines were measured and compared with glioma and PCNSL. RESULTS The subjects were 53 glioma patients and 24 PCNSL patients. There were 22 types of significant differences between glioma and PCNSL, 18 with high PCNSL and 4 with high glioma. In addition to IL-10, which has been reported so far, the significant higher concentrations in PCNSL was found in Osteopontin, TNFSF8, TNFSF12, TNFSF13, TNFSF13B, TNFSF14, sTNF-R1, sTNF-R2, IL-6Ra, IL-8, IL-12(p40), IL-20, IL-27, sCD163, MMP2, MMP3, CHI3L1. On the other hand, IL-2, Il-12(p70), IL-22, and MMP-1 levels were significant higher in CSF in glioma. Although CD163 is an important molecule as a marker for M2 macrophages, immunostaining of tissues showed no significant difference in infiltration between Glioblastoma and PCNSL. This suggests that M2 macrophages infiltrating PCNSL and Glioblastoma have different activation states. CONCLUSION PCNSL had higher levels of inflammatory mediators such as TNF-related molecules. PCNSL was significantly higher in sCD163 than in glioblastoma, suggesting different activation of intratumoral M2 macrophages.

Primary central nervous system malignant lymphoma in a patient with rheumatoid arthritis receiving tocilizumab: illustrative case.

Although the risk of developing malignant lymphoma is higher in patients with rheumatoid arthritis (RA) than in the general population, primary central nervous system lymphoma (PCNSL) in patients with RA is extremely rare. In recent years, there has been concern that biological disease-modifying antirheumatic drugs (bDMARDs), widely administered to patients with RA, might increase the risk of cancer development. The authors report the first case of PCNSL in a patient with RA receiving the bDMARD tocilizumab. A 70-year-old man who was diagnosed with RA in 2010 was treated with low-dose methotrexate (MTX) from 2010 to 2015. Tocilizumab was commenced in 2012. In 2018, he developed gait disturbances, and gadolinium-enhanced magnetic resonance imaging showed multiple contrast-enhanced lesions in the basal ganglia and brain stem. Stereotactic brain biopsy led to the diagnosis of diffuse large B-cell lymphoma, and finally PCNSL was diagnosed. He was treated with five courses of MTX 3.5 g/m2, and his disease has been in remission for 34 months. Low-dose MTX and bDMARDs are associated with the concern of increased cancer risk in patients with RA. Because tocilizumab has been in use for a relatively short time, further accumulation of cases and careful follow-up are necessary.

ML-13 Primary central nervous system malignant lymphoma in a patient with rheumatoid arthritis receiving tocilizumab

Background: Although the risk of developing malignant lymphoma is higher in patients with rheumatoid arthritis (RA) than in the general population, the occurrence of primary central nervous system lymphoma (PCNSL) in patients with RA is extremely rare. In recent years, there has been concern that biological disease-modifying antirheumatic drugs (DMRADs), which are widely administered to patients with RA, may increase the risk of developing cancer. We report the first case of PCNSL in a patient with RA who was treated with the biological DMRADs, tocilizumab. Case description: A 70-year-old man, who was diagnosed with RA in 2010 was treated with low-dose methotrexate from 2010 to 2015. He was started on tocilizumab in 2012. In 2018, he suffered from gait disturbance and was diagnosed with lumbar spinal stenosis. He underwent L2/3 posterior fusion surgery, but his paraplegia gradually deteriorated. Two months after the surgery, a head Gd-MRI showed multiple contrast-enhanced lesions in the basal ganglia and brain stem. A stereotactic brain biopsy was performed and DLBCL was diagnosed, and finally PCNSL was diagnosed because of no neoplastic lesions in other organs. He was treated with 5 courses of MTX 3.5g/m2 with rituximab and has been in remission for 23 months. He has maintained an independent life with residual paraplegia, but his ADLs gradually worsened. He was restarted on tocilizumab with a diagnosis of worsening RA. Conclusion: Low-dose methotrexate and biological DMRADs including tocilizumab, have been concerned to increase the risk of cancer in patients with RA, but there is no solid evidence. Since it has been a short time since the use of biological DMRADs, further accumulation of cases and careful follow-up are necessary.

The Real-World status and risk factors for a poor prognosis in elderly patients with primary central nervous system malignant lymphomas: a multicenter, retrospective cohort study of the Tohoku Brain Tumor Study Group.

Elderly patients with primary central nervous system malignant lymphoma (EL-PCNSL) may not be given sufficient treatment due to their poor pre-treatment Karnofsky Performance Status (KPS) and comorbidities. Therefore, a retrospective, cohort study was performed to evaluate risk factors associated with a poor prognosis of EL-PCNSL in the Tohoku Brain Tumor Study Group. Patients aged ≥ 71years with PCNSL were enrolled from eight centers. Univariate analysis was performed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Three of the total 142 cases received best supportive care (BSC). Treatment was given to 30 cases without a pathological diagnosis, 3 cases with cerebrospinal fluid (CSF) cytology, and 100 cases with a pathological diagnosis. After confirmation of no differences in progression-free survival (PFS) and overall survival (OS) between the group treated without pathology and the groups diagnosed by pathology or CSF cytology and between median age ≥ 76years and < 76years, a total of 133 patients were studied. The median pre-treatment KPS was 50%. Median PFS and median OS were 16 and 24months, respectively. Risk factors associated with poor prognosis on Cox proportional hazards model analysis were pre-treatment cardiovascular disease and central nervous system disease comorbidities, post-treatment pneumonia and other infections, and the absence of radiotherapy or chemotherapy. Pre-treatment comorbidities and post-treatment complications would affect the prognosis. Radiation and chemotherapy were found to be effective, but no conclusions could be drawn regarding the appropriate content of chemotherapy and whether additional radiotherapy should be used.

ML-23 The outcome of malignant lymphoma of the central nervous system in a single institution

Background: Although high dose-methotrexate therapy has been performed for primary central nervous system malignant lymphoma (PCNSL), R-MPV (rituximab, methotrexate (MTX), procarbazine and vincristine) therapy is currently the first line therapy for (PCNSL) in our hospital. This study examines the results of R-MPV therapy comparing with past treatment. Method/Subjects: Thirty-seven patients treated at our hospital from 2009 to 2020 were included. Overall survival time, progression free survival time, and toxicities were evaluated. Results: The average age of patients was 65.7 years. Patients included 21 males and 16 females. Thirty-six patients were diagnosed DLBCL by resected brain tumor tissues, and one was diagnosed DLBCL by vitreous biopsy. As initial treatment, rituximab±HD-MTX therapy (R±MTX group) was performed in 20 cases, HD-MTX therapy plus radiation (R±MTX+RT group) was performed in 12 cases, and RMPV therapy was performed in 5 cases (R-MPV group). Median OS of all cases was 69 months and median PFS was 38 months. Median OS was 69 months in R±MTX group and could not be calculated in R±MTX+RT, and R-MPV groups. Median PFS was 16 months and 56 months in R±MTX group and R±MTX+RT, respectively, and could not be calculated in the R-MPV group. Although the R-MPV group had a short follow-up period, the results were considered to be comparable to those of the R±MTX+RT group. On the other hand, grade 3/4 adverse events occurred in 50%, 25%, and 100%, respectively. Conclusion: R-MPV therapy may delay the timing of radiation and reduce the amount of radiation. On the other hand, the frequency of adverse events is high, and more strict management of treatment is required.

Subcutaneous Metastasis due to Primary Central Nervous System Malignant Lymphoma

© 2009 The Authors. doi: 10.2340/00015555-0640 Journal Compilation © 2009 Acta Dermato-Venereologica. ISSN 0001-5555 Sir, Primary central nervous system malignant lymphoma (PCNSL) is a rare non-Hodgkin’s lymphoma. Although it accounts for less than 1% of cases of non-Hodgkin’s lymphoma, its incidence is increasing due to the ageing society (1). Histologically, the main type of PCNSL is diffuse large B-cell lymphoma (DLBCL). Local recurrence of PCNSL has often been observed, but skin metastasis of PCNSL is rare, only one case of skin metastasis having been reported previously (2). We report here a case of PCNSL with subcutaneous metastasis on the forearm.

脳炎症状で発症し中枢神経原発悪性リンパ腫が疑われた透析患者の１例

脳炎症状で発症し中枢神経原発悪性リンパ腫が疑われた透析患者の１例

Primary Ki-1 lymphoma in the central nervous system

Large cell anaplastic malignant lymphoma with Ki-1 (CD30) antigen is a new entity among human non-Hodgkin's malignant lymphomas according Updated Kiel Classification and is also a very rare subtype in primary central nervous system (CNS) malignant lymph omas. The precise clinical characteristics and the significance of Ki-1 antigen have yet to be clarified. The authors herein report a case of Ki-1 positive primary T-cell CNS malignant lymphoma. A 49-year-old man presented with multiple mass lesions in t he brain on MRI. Immunohistochemical investigations of biopsy specimens from the superior medullary velum revealed a large cell anaplastic T-cell lymphoma positive for Ki-1 antigen. After administering extensive chemo-radiotherapy, the patient has surviv ed for more than 42 months after the onset of symptoms.

Telomerase activity in central nervous system malignant lymphoma

Primary central nervous system malignant lymphoma (PCNSL) has been regarded as a rare neoplasm. Recently, however, its incidence has been rapidly increasing. Despite active clinical trials, its clinical and biologic features remain unknown and there has been no effective treatment or prognostic factor. The current study attempted to elucidate telomerase activity and expression of the telomere-related RNA of PCNSL as novel prognostic factors. The subjects were 12 patients with histologically diagnosed PCNSL. All patients were treated with chemoradiotherapy consisting of whole-brain radiation, vincristine, etoposide, and prednisolone. Telomerase activity in the resected tumor was analyzed both qualitatively and quantitatively using the TRAP (telomeric amplification assay protocol)/TRAP-HPA (hybridization protection assay) method. The expression of telomere-related RNA (hTERT, hTERC, and TEP1) was analyzed by reverse transcriptase-polymerase chain reaction. Telomerase activity was detected in 10 of 12 patients with PCNSL, with an average activity of 148.9 relative light units. The average telomere length was 5.55 kb. The expression of hTERT correlated with telomerase activity, and there was a statistically significant correlation between telomerase activity and both the duration of survival and the interval to tumor progression. Telomerase activity and the expression of hTERT may be novel prognostic factors in patients with PCNSL.

Telomerase activity in central nervous system malignant lymphoma

Telomerase activity in central nervous system malignant lymphoma

Radiographic Features of Granulocytic Sarcoma (Chloroma)

The computed tomographic (CT) findings in two patients in whom intracranial granulocytic sarcomas preceded the onset of systemic myelogenous leukemia are presented. On CT, granulocytic sarcomas may be indistinguishable from meningiomas and difficult to differentiate from primary central nervous system malignant lymphoma and eosinophilic granuloma.