scholarly journals Distinct microRNA expression signatures of primary and secondary central nervous system lymphomas

2021 ◽  
Author(s):  
Endre Sebestyén ◽  
Ákos Nagy ◽  
Dóra Marosvári ◽  
Hajnalka Rajnai ◽  
Béla Kajtár ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mirna Expression ◽  
Molecular Subtype ◽  
Expression Patterns ◽  
Primary Cns Lymphoma ◽  
Future Research ◽  
Cns Lymphoma ◽  
Clustering Methods ◽  
Therapeutic Implications

AbstractCentral nervous system (CNS) lymphoma is a rare and aggressive non-Hodgkin lymphoma that might arise in the CNS (primary CNS lymphoma, PCNSL) or disseminates from a systemic lymphoma to the CNS (secondary CNS lymphoma, SCNSL). Dysregulated expression of microRNAs (miRNAs) is associated with various pathological processes and miRNA expression patterns may have diagnostic, prognostic and therapeutic implications. However, miRNA expression is understudied in CNS lymphomas. Here, we performed expression analysis of 798 miRNAs in 73 CNS lymphoma samples using the NanoString platform, followed by a detailed statistical analysis to identify potential novel biomarkers characterizing subgroups and to examine differences based on their primary and secondary nature, molecular subtype, mutational patterns and survival. We describe the general expression patterns of miRNAs across CNS lymphoma samples and identified 31 differentially expressed miRNAs between primary and secondary groups. Additionally, we identified 7 more miRNAs associated with a molecular subtype and 25 associated with mutation status. Using unsupervised clustering methods, we defined a small but distinct primary CNS lymphoma subgroup, with characteristically different expression patterns compared to the rest of the cases. Finally, we identified differentially regulated pathways in the above comparisons and assessed the utility of miRNA expression patterns in predicting survival. Our study identifies a novel CNS lymphoma subgroup defined by distinct miRNAs, proves the importance of specific miRNAs and pathways in their pathogenesis, and provides the basis for future research.

scholarly journals Differential expression of N-linked oligosaccharides in methotrexate-resistant primary central nervous system lymphoma cells

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yasuo Takashima ◽  
Takeshi Yoshimura ◽  
Yuichiro Kano ◽  
Azusa Hayano ◽  
Hiroaki Hondoh ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Differential Expression ◽  
Expression Patterns ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
High Mannose ◽  
Cns Lymphomas ◽  
Resistant Cells

Abstract Background Oligosaccharides of glycoprotein, particularly negatively-charged sialylated N-glycans, on the surface of lymphomas play important roles in cell–cell interactions and bind immunoglobulin-like lectins, causing inflammatory responses and bioregulation. However, their characterizations have largely been unknown in central nervous system (CNS) lymphoma. Methods Here, we investigated expression patterns of N-linked oligosaccharides of glycoproteins in cells derived from CNS lymphomas and clinical specimens. Results We first generated methotrexate (MTX)-resistant cells derived from HKBML and TK as CNS lymphoma, and RAJI as non-CNS lymphoma and determined N-linked oligosaccharide structures in these cells and other non-CNS lymphoma-derived cells including A4/FUK, OYB, and HBL1. Major components of the total oligosaccharides were high-mannose type N-glycans, whose level increased in MTX-resistant HKBML and TK but decreased in MTX-resistant RAJI. We also detected sialylated biantennary galactosylated N-glycans with α1,6-fucosylation, A2G2F, and A2G2FB from HKBML, TK, and RAJI. Sialylated A4G4F was specifically isolated from RAJI. However, the ratios of these sialylated N-glycans slightly decreased against MTX-resistant compared to non-resistant cells. Interestingly, almost all complex-type oligosaccharides were α2,6-sialylated. Discussion This is the first study for the expression profile of N-oligosaccharides on MTX-resistant primary CNS lymphoma-derived cells HKBML and TK, and tumor tissues resected from patients with CNS lymphoma, Conclusion These results propose a possibility that the differential expression of high-mannose types and sialylated A2G2F, A2G2FB, and A4G4F on the surface of CNS lymphomas may provide a hint for targets for diagnoses and treatments of the oligosaccharide type-specific lymphomas.

scholarly journals Consensus Recommendations for MRI and PET Imaging of Primary Central Nervous System Lymphoma: Guideline Statement from the International Primary CNS Lymphoma Collaborative Group (IPCG)

2021 ◽  
Author(s):  
Ramon F Barajas Jr ◽  
Letterio S Politi ◽  
Nicoletta Anzalone ◽  
Heiko Schöder ◽  
Christopher P Fox ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Tumor Imaging ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Response Assessment ◽  
Integrated Approach ◽  
Collaborative Group ◽  
Cns Lymphoma ◽  
Consensus Recommendations

Abstract Advanced molecular and pathophysiologic characterization of Primary Central Nervous System Lymphoma (PCNSL) has revealed insights into promising targeted therapeutic approaches. Medical imaging plays a fundamental role in PCNSL diagnosis, staging, and response assessment. Institutional imaging variation and inconsistent clinical trial reporting diminishes the reliability and reproducibility of clinical response assessment. In this context, we aimed to: 1) critically review the use of advanced PET and MRI in the setting of PCNSL; 2) provide results from an international survey of clinical sites describing the current practices for routine and advanced imaging, and 3) provide biologically based recommendations from the International PCNSL Collaborative Group (IPCG) on adaptation of standardized imaging practices. The IPCG provides PET and MRI consensus recommendations built upon previous recommendations for standardized brain tumor imaging protocols (BTIP) in primary and metastatic disease. A biologically integrated approach is provided to addresses the unique challenges associated with the imaging assessment of PCNSL. Detailed imaging parameters facilitate the adoption of these recommendations by researchers and clinicians. To enhance clinical feasibility, we have developed both “ideal” and “minimum standard” protocols at 3T and 1.5T MR systems that will facilitate widespread adoption.

Lymphomatous meningitis in primary central nervous system lymphoma

2006 ◽  
Vol 21 (5) ◽  
pp. 1-7 ◽  
Author(s):  
Marc C. Chamberlain
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Drug Therapy ◽  
Mr Imaging ◽  
Primary Cns Lymphoma ◽  
Chemotherapeutic Agents ◽  
Cranial Computed Tomography ◽  
Cns Lymphoma ◽  
High Dose ◽  
Lymphomatous Meningitis

✓Lymphomatous meningitis (LM) due to primary central nervous system (CNS) lymphoma is an uncommon problem in neurooncology and can occur at time of diagnosis or recurrence. Notwithstanding frequent focal signs and symptoms, LM is a disease affecting the entire neuraxis, and therefore staging and treatment need to encompass all cere-brospinal fluid (CSF) compartments. Central nervous system staging of LM includes contrast agent–enhanced cranial computed tomography (CT) or Gd-enhanced magnetic resonance (MR) imaging, Gd-enhanced spinal MR imaging, CT myelography, and radionuclide CSF flow study. Treatment of LM includes involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy can benefit patients with LM and can obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (methotrexate, cytosine arabinoside, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of LM is palliative and the expected median survival of patients is 4 to 6 months, it often provides stabilization and protection from further neurological deterioration. In patients with primary CNS lymphoma, CNS prophylaxis has been recommended (using a combination of high-dose systemic chemotherapy and intra-CSF chemotherapy), but the strategy remains controversial because high-dose systemic methotrexate is commonly used as an adjuvant therapy. Patients with primary CNS lymphoma at high risk as defined by positive CSF cytology or neuroradiography consistent with LM may benefit from the inclusion of intra-CSF chemotherapy.

scholarly journals Cerebrospinal Fluid Flow Cytometry: Utility in Central Nervous System Lymphoma Diagnosis

2020 ◽  
Vol 47 (3) ◽  
pp. 382-388
Author(s):  
Ka Loong Kelvin Au ◽  
Sarah Latonas ◽  
Afshin Shameli ◽  
Iwona Auer ◽  
Christopher Hahn
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Hematological Malignancy ◽  
Previous History ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Csf Flow ◽  
Neurologic Symptoms

ABSTRACT:Background:Flow cytometry of the cerebrospinal fluid (CSF) is used in isolation or as an adjunct to cytology to increase the sensitivity of detecting central nervous system (CNS) lymphoma. We aimed to evaluate the sensitivity of CSF flow cytometry as a diagnostic screening tool for primary CNS lymphoma in patients presenting with undifferentiated neurologic symptoms.Methods:We retrospectively reviewed all CSF samples received by the Calgary Laboratory Services Flow Cytometry Laboratory from 2012 to 2015. Clinical data, laboratory investigations, radiologic imaging studies, and pathological data were analyzed. Clinical review extended to 2 years post-CSF flow cytometric testing.Results:Only 43/763 (5.6%) samples of CSF flow cytometry in 28/573 (4.9%) patients were found to be positive for a hematological malignancy in patients with undifferentiated neurologic symptoms. The overall sensitivity of the test was 13.8% with 25 patients with negative CSF flow cytometry later having a positive biopsy for CNS lymphoma. CSF flow cytometry was negative in all cases when at the time of CSF examination the patient did not have a previous hematological malignancy or findings of abnormal enhancement on MRI (n = 249).Conclusion:CSF flow cytometry has low utility in screening for primary CNS lymphoma in the absence of a previous history of hematologic malignancy or findings of abnormal enhancement on MRI.

Primary malignant lymphoma in the cerebellopontine angle

1998 ◽  
Vol 112 (5) ◽  
pp. 476-479 ◽  
Author(s):  
Shin Kariya ◽  
Kazunori Nishizaki ◽  
Katsuya Aoji ◽  
Hirofumi Akagi
Keyword(s):  
Central Nervous System ◽  
Rectal Cancer ◽  
Nervous System ◽  
Malignant Lymphoma ◽  
Cerebellopontine Angle ◽  
Primary Cns Lymphoma ◽  
Cns Lymphoma ◽  
Immunocompromised Patients ◽  
Uncommon Disease ◽  
The Central Nervous System

AbstractPrimary malignant lymphoma is an uncommon disease of the central nervous system (CNS). Immunocompromised patients are at high risk of development of malignant lymphoma. We describe a case of primary CNS lymphoma presenting as a solitary cerebellopontine angle lesion. The patient had undergone extirpation of rectal cancer four years previously. Malignant lymphoma presenting as a cerebellopontine angle mass is extremely rare, with only 10 such cases (seven were primary, and the others secondary) previously reported.

scholarly journals Molecular Subtypes and Genomic Profile of Primary Central Nervous System Lymphoma

2019 ◽  
Vol 79 (2) ◽  
pp. 176-183
Author(s):  
Csaba Bödör ◽  
Donát Alpár ◽  
Dóra Marosvári ◽  
Bence Galik ◽  
Hajnalka Rajnai ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Target Genes ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Central Nervous System Lymphoma ◽  
Diagnostic Algorithm ◽  
Molecular Classification ◽  
Cns Lymphoma

Abstract Primary central nervous system lymphomas (PCNSL) are aggressive non-Hodgkin lymphomas affecting the central nervous system (CNS). Although immunophenotyping studies suggested an uniform activated B-cell (ABC) origin, more recently a spectrum of ABC and germinal center B-cell (GC) cases has been proposed, with the molecular subtypes of PCNSL still being a matter of debate. With the emergence of novel therapies demonstrating different efficacy between the ABC and GC patient groups, precise assignment of molecular subtype is becoming indispensable. To determine the molecular subtype of 77 PCNSL and 17 secondary CNS lymphoma patients, we used the NanoString Lymphoma Subtyping Test (LST), a gene expression-based assay representing a more accurate technique of subtyping compared with standard immunohistochemical (IHC) algorithms. Mutational landscapes of 14 target genes were determined using ultra-deep next-generation sequencing. Using the LST-assay, a significantly lower proportion (80% vs 95%) of PCNSL cases displayed ABC phenotype compared with the IHC-based characterization. The most frequently mutated genes included MYD88, PIM1, and KMT2D. In summary, we successfully applied the LST-assay for molecular classification of PCNSL, reporting higher proportion of cases with GC phenotype compared with IHC analyses, leading to a more precise patient stratification potentially applicable in the diagnostic algorithm of PCNSL.

Rituximab Cerebrospinal Fluid Levels in Patients with Primary Central Nervous System Lymphoma Treated with Intravenous High Dose Rituximab

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1644-1644 ◽  
Author(s):  
Jean-Francois Larouche ◽  
Marc Bergeron ◽  
Grace Hampson ◽  
Tim Illidge ◽  
Robert Delage
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Serum Levels ◽  
Cns Lymphoma ◽  
High Dose ◽  
Serum Samples ◽  
Cerebrospinal Fluid Levels ◽  
Fluid Levels

Abstract Abstract 1644 INTRODUCTION: Rituximab penetration in central nervous system is largely unknown in human. Experiments in monkeys showed that 0,1% of serum rituximab concentration was achieved in cerebrospinal fluid. Reports in patients are limited (Rubenstein JL, Blood 2003 and Petereit HF, Multiple Sclerosis 2009). They demonstrated similar low levels of cerebrospinal fluid penetration with standard dose (375 mg /m2) rituximab in patients with central nervous system (CNS) lymphoma or multiple sclerosis. METHOD: We conducted a phase 2 trial in patients with primary CNS lymphoma. Patients were treated with an intravenous combination of high dose methotrexate (8 g/m2), high dose cytarabine (2 g/m2) and high dose rituximab (750 mg/m2 every 1–2 weeks × 13 infusions). We obtained from four patients paired cerebrospinal fluid and serum samples and rituximab concentration were determined in each. Samples were collected at different time points just before rituximab infusion and represent trough levels. RESULTS: 11 cerebrospinal fluid samples were available and their 11 paired serum samples. Mean cerebrospinal fluid and serum levels were 2,04 ug/mL (0,49–4,08) and 297,09 ug/mL (211,26–504,47) respectively. Mean cerebrospinal fluid levels were 0,71% (0,18–1,5%) of serum levels. No relationship was made between cerebrospinal fluid level and the number of rituximab dose administered. CONCLUSION: In patients with primary CNS lymphoma receiving high dose 1–2 weekly rituximab. cerebrospinal fluid concentration achieve is low compared to serum levels. However, administration of higher dose of intravenous rituximab can increase penetration in central nervous system but its clinical impact is unknown as cerebrospinal fluid levels are still low. Disclosures: No relevant conflicts of interest to declare.

scholarly journals P14.84 Intraarterial chemotherapy and osmotic blood-brain barrier modification in the treatment of primary CNS lymphoma

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii87-iii87
Author(s):  
D Fortin ◽  
G Gahide ◽  
C Iorio-Morin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Primary Cns Lymphoma ◽  
Brain Barrier ◽  
Cns Lymphoma ◽  
High Dose ◽  
Left Internal Carotid Artery ◽  
Single Center ◽  
Blood Brain

Abstract BACKGROUND Primary central nervous system lymphomas (PCNSL) are considered a rare and aggressive form of central nervous system (CNS) tumors. High-dose methotrexate has become the backbone of PCNSL treatment, and is recommended by the EANO guidelines. In most recent protocols, investigators tend to postpone or even avoid the use of radiotherapy; indeed, its use has become controversial with findings of associated severe neuro-toxicity, especially in elderly patients. To maximize delivery across the BBB, we use cerebral intra-arterial chemotherapy (CIAC) coupled with osmotic blood-brain barrier disruption (OBBBD). We hereby report our single-center experience over 18 years with the CIAC + BBBD technique using 2 different HD-MTX protocols. MATERIAL AND METHODS This phase II study was conducted at the Centre hospitalier Universitaire de Sherbrooke (CHUS) from November 1999 to May 2018. The protocol was approved by the institutional review board, and informed consent was obtained in accordance to institutional regulation in every patient After enrollment and initial evaluation, patients were treated every four weeks (1 cycle) for 12 cycles, unless progression. After general anesthesia, a transfemoral approach was used to catheterize either the right or left internal carotid artery or the dominant vertebral artery, depending on tumor(s) location. OBBBD was performed by infusing 20% mannitol in the selected vascular distribution for 30 seconds at a rate that fills the vascular distribution so as to maximize the contact of the mannitol with the endothelial cells.Two different chemotherapy regimens were sequentially used in this study. High-dose MTX (5 g IV) was the cornerstone of both regimens: the first regimen (1999 to 2007) also included etoposide phosphate IV (400 mg/m²) and cyclophosphamide IV (660 mg/m²), whereas the 2nd regimen (1998 to 2018) also included carboplatin IA (400 mg/m²). RESULTS The present analysis therefore concerns a cohort of 44 naive patients recruited over 18 years in a single center. Median follow-up was 38 months. Overall, a CR was induced in 34 patients (79%). Themedian time to CR was 7.3 months (IQR: 7.8). Of these 34 patients, 11 (25.6%) are still alive, and 9 of these are disease-free after treatment discontinuation. The actuarial median survival (MS) was 46.5 months (95% CI: 30.9–62.2) for the cohort. Survival was 88%, 64%, 54%, 39% and 18% at 1, 2, 3,5 and 10 years (Figure 1 and Table 2).The progression-free survival was 43.4 months (95% CI: 17.9–68.9). Five occurrences of vascular complications related to the treatment were observed (11.6%). Conclusion: CIAC HD-MTX-based protocols with OBBBD is a safe and well-tolerated procedure for the management of primary CNS lymphoma. Our single center data suggests better PFS and survival outcomes compared to IV protocols with less hematologic toxicity and good tolerability, especially in the elderly.

Intraoperative 5-aminolevulinic acid–induced fluorescence in primary central nervous system lymphoma

2014 ◽  
Vol 120 (1) ◽  
pp. 67-69 ◽  
Author(s):  
Rachel Grossman ◽  
Erez Nossek ◽  
Nir Shimony ◽  
Michal Raz ◽  
Zvi Ram
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Fourth Ventricle ◽  
Aminolevulinic Acid ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
Fluorescence Pattern ◽  
Intense Fluorescence ◽  
Preoperative Administration

The authors report a case of primary CNS lymphoma located in the floor of the fourth ventricle that showed intense fluorescence after preoperative administration of 5-aminolevulinic acid. The authors believe that this is the first demonstration of a 5-aminolevulinic acid–induced fluorescence pattern in primary CNS lymphoma.

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