scholarly journals Brain stereotactic biopsy flow cytometry for central nervous system lymphoma characterization: advantages and pitfalls

2016 ◽  
Vol 35 (1) ◽  
Author(s):  
Iole Cordone ◽  
Serena Masi ◽  
Mariantonia Carosi ◽  
Antonello Vidiri ◽  
Francesco Marchesi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Stereotactic Biopsy ◽  
Central Nervous System Lymphoma

scholarly journals P14.49 Primary central nervous system lymphoma presenting as dementia: do not forget IL10 in CSF analysis

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii78-iii78
Author(s):  
A Blain ◽  
A Brinet ◽  
M Berthel ◽  
A Camoyret ◽  
C Gaultier ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Symptom Onset ◽  
Clinical Presentation ◽  
Diagnostic Delay ◽  
Central Nervous System Lymphoma ◽  
Treatment Modalities ◽  
Progressive Dementia ◽  
Csf Analysis

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) is a rare form of non-Hodgkin lymphoma that affects the central nervous system without systemic involvement. Clinical presentation depends on its localization: Focal deficits usually lead to prompt neuroradiologic evaluation, whereas cognitive or behavioral changes can lead to diagnostic delay. Rapidly progressive dementia (RPD), defined as a 1- to 2-year course from symptom onset to cognitive and functional debilitation, is a clinical presentation of PCNSL and thus a potentially curable cause of dementia, leading to death if it remains untreated. Nevertheless, its diagnosis is frequently delayed as other origins (CJD, autoimmune, paraneoplastic, infectious, and neurodegenerative disorders) are more frequently considered. We aimed to describe diagnostic features and treatment modalities in a series of patients presenting with RPD diagnosed as PCNSL. METHODS Patients with RPD and final diagnosis of PCNSL were retrospectively identified from 2012 to 2019 from the database of our academic teaching hospital. Clinical presentation, neuroimaging, and cerebro-spinal fluid (CSF) analysis were assessed from their medical records. Interleukin (IL) 10 and 6 concentrations were measured by flow cytometry using the cytometric bead array (CBA) technique (BD Biosciences) with a detection limit set at 2.5 pg/ml. RESULTS 50 patients with diagnosis of PCNSL were identified, 7 (3 women, 4 men) presented with RPD.Median age was 69 years (range 59–84). Time from symptom onset to diagnostic confirmation of PCNSL ranged from 1–12 months (median 3). All patients presented with cognitive impairment (disorientation, memory disorders), accompanied by psycho-behavioral disorders in 6 of them. MRI disclosed enhancing lesions in all patients. Lumbar puncture was performed in 5 patients. All of them presented pleiocytosis, and lymphomatous meningitis was detected in 4/5 of them by cytology or flow cytometry (FCM). Elevated interleukin 10 (IL-10) was found in all patients with available CSF sample, 4 of them had an IL-10/IL-6 ratio >1. DISCUSSION AND CONCLUSION Patients presenting with rapidly progressive dementia should be evaluated for treatable forms of dementia. PCSNL has to be considered as soon as possible as diagnostic delay impacts its outcome. Imaging studies, usually contrast-enhanced MRI, is recommended, although nonspecific findings are not uncommon, especially in case of non-enhancing lesions. CSF sampling can help to prove diagnosis of PCNSL by cytology (generally associated with FCM), but it requires an experienced cytologist and immediate sample analysis.IL10 and IL10/6 ratio can be used as a more easily available marker to support suspicion of PNSCL, leading to further specific workup. ACKNOWLEDGMENTS NENO & LOC Network

scholarly journals IMMU-50. BBB CROSSING NANO-IMMUNOMEDICINE COMBINATION THERAPY TO TREAT BRAIN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii115-ii115
Author(s):  
Tao Sun ◽  
Jiyuan Yang ◽  
Maximilian Gamburg ◽  
Vladimir Ljubimov ◽  
Zachary Grodzinski ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Ex Vivo ◽  
Central Nervous System Lymphoma ◽  
Phase Iii ◽  
Spectral Flow ◽  
Rna Seq ◽  
M1 Macrophage ◽  
Synthesis Strategy

Abstract INTRODUCTION Lack of standard treatment of Primary Central Nervous System Lymphoma (PCNSL) was acknowledged in phase III intergroup study (HOVON 105/ALLG NHL 24). PCNSL incidence is increasing for unknown reasons, particularly among persons over 65 years. One of the major limitations of successful treatment of PCNSL is the blood-brain barrier (BBB), which prevents drug delivery into the brain. METHODS Polymer nanoconjugate based on biodegradable poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) was used for treatment of BALB/C mice with intracranially inoculated murine A20 lymphoma. PHPMA-based nanoconjugates have defined synthesis strategy for BBB transcytosis, tumor targeting, and cancer cell killing. Nano immunodrug PHPMA/AP-2/Fab’/c-Myc inhibitor/H6 conjugate contains multiple AP-2 peptides for efficient delivery across the BBB and Fab’ fragments of αCD20 mouse Ab for CD20 receptor crosslinking on PCNSL cells. c-Myc inhibitor bound via a disulfide bond is transferred to the cytoplasm followed by cleavage. The therapeutic efficacy and survival were evaluated together with spectral flow cytometry and RNA-seq bioinformatic analysis of tumor tissues. RESULTS Nanoconjugates were able to penetrate BBB and accumulate in brain parenchyma. The best survival results were obtained for the group where nanoconjugate with αCD20 Fab’ causing tumor cell apoptosis and c-Myc antisense inhibitor was combined with αPD-1 checkpoint inhibitor. Survival compared to PBS-treated controls was significant (P=0.0006 by ANOVA). Ex vivo analysis of A20 brain lymphoma tissue after treatment with nanoconjugates demonstrated reduction of Tregs, associated with downregulation of IL-10 and IL-1β in plasma. Spectral flow cytometry revealed activation of tumor infiltrating T lymphocytes and M1 macrophages in lead nanodrug treated groups. RNA-seq data correlated with flow cytometry results indicating the activation of genes linked to IFN-γ pathway important for anti-tumor response and M1 macrophage activation. Immunostaining confirmed a marked increase of M1-specific iNOS expression in the nanodrug-treated tumors. Support: NIH grants: R01 CA188743, R01 CA206220, R01 CA209921

Central nervous system lymphoma: Patterns of incidence in Indian population and effect of steroids on stereotactic biopsy yield

2014 ◽  
Vol 62 (1) ◽  
pp. 19 ◽  
Author(s):  
A Arivazhagan ◽  
HR Arvinda ◽  
DhananjayaI Bhat ◽  
BA Chandramouli ◽  
BIndira Devi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Indian Population ◽  
Stereotactic Biopsy ◽  
Central Nervous System Lymphoma

scholarly journals Utility of Flow Cytometry of Cerebrospinal Fluid as a Screening Tool in the Diagnosis of Central Nervous System Lymphoma

2013 ◽  
Vol 137 (11) ◽  
pp. 1610-1618 ◽  
Author(s):  
Meredith Pittman ◽  
Susan Treese ◽  
Ling Chen ◽  
John L. Frater ◽  
TuDung T. Nguyen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Predictive Value ◽  
Central Nervous System Lymphoma ◽  
Brain Biopsy ◽  
Predictive Values ◽  
History Of

Context.—Experiences at our institution show that flow cytometry analysis (FCA) has become routine clinical practice in the workup of patients with altered mental status, even if risk factors are low. Objective.—To assess diagnostic accuracy of combined FCA and cytology in the diagnosis of central nervous system lymphoma in an unselected patient population with neurologic symptoms, including patients with no history of lymphoma or suspicious radiology. Design.—Between 2001 and 2011, cerebrospinal fluid was submitted from 373 patients for lymphoma screening by FCA. The medical records were reviewed for patient symptomatology, history of malignancy, brain imaging, FCA results, cytology results, brain biopsy, and clinical follow-up. Results.—A lymphoid malignancy was detected by FCA in 4% of cases. A positive diagnosis was more likely in patients with either a history of hematologic malignancy and/or a suspicious radiology result (P = .009). All patients with no history of lymphoma and no suspicious radiology (n = 102) had negative cytology, and none had a correspondingly positive FCA result. The positive and negative predictive values of combined cytology and FCA in the patients with history of lymphoma and/or abnormal imaging results were 92% and 89%, respectively, when compared with open brain tissue biopsy, and 89% and 86%, respectively, when compared with clinical follow-up. When low-risk patients were included, the positive predictive value remained at 92%, but the negative predictive value dropped to 52% with the open brain biopsy as the reference, and values did not change significantly for the group with clinical follow-up. Conclusions.—Concurrent FCA and cytology are most useful in the appropriate clinical setting, and we propose a triage algorithm for how FCA on cerebrospinal fluid is best used.

scholarly journals P.046 Flow cytometry in cerebrospinal fluid: utility in the diagnosis of central nervous system lymphoma

2018 ◽  
Vol 45 (s2) ◽  
pp. S27-S27
Author(s):  
K Au ◽  
S Latonas ◽  
A Shameli ◽  
I Auer ◽  
C Hahn
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Hematological Malignancy ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Prior History ◽  
Cns Lymphoma ◽  
Csf Flow

Background: Flow cytometry in the cerebrospinal fluid (CSF) is used as an adjunct to cytology to increase the sensitivity of detecting central nervous system (CNS) lymphoma. We aim to evaluate CSF flow cytometry as a diagnostic tool for lymphoma in patients presenting with undifferentiated neurologic symptoms. Methods: We retrospectively reviewed all CSF flow cytometry samples sent in the Calgary region from 2012-2015. Clinical data, laboratory investigations, radiologic imaging studies, and pathological data were analyzed. Clinical review extended to 2 years post CSF flow cytometric testing. Results: The number of samples of CSF flow cytometry that were positive for a hematological malignancy was 43/763 (5.6%). The overall sensitivity of the test was 72.9%. A positive result was more likely to occur in patients with a prior history of a hematological malignancy or abnormal enhancement on MRI (p<0.0001). In fact, CSF flow cytometry was negative in all patients who did not have a previous hematological malignancy or abnormal enhancement on MRI (n = 247). Conclusions: CSF flow cytometry has very limited role in the screening for primary CNS lymphoma, unless a strictly endorsed testing algorithm is applied. It is, however, an invaluable tool in assessing CNS involvement in patients with previous diagnosis of hematolymphoid malignancy.

scholarly journals A Multiplex Assay for the Stratification of Patients with Primary Central Nervous System Lymphoma Using Targeted Mass Spectrometry

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1732
Author(s):  
Daniel M. Waldera-Lupa ◽  
Gereon Poschmann ◽  
Nina Kirchgaessler ◽  
Omid Etemad-Parishanzadeh ◽  
Falk Baberg ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Diagnostic Accuracy ◽  
Tumor Tissue ◽  
Stereotactic Biopsy ◽  
Area Under The Curve ◽  
Central Nervous System Lymphoma ◽  
Tissue Analysis ◽  
Novel Biomarkers

Primary central nervous system lymphomas (PCNSL) account for approximately 2% to 3% of all primary brain tumors. Until now, neuropathological tumor tissue analysis, most frequently gained by stereotactic biopsy, is still the diagnostic gold standard. Here, we rigorously analyzed two independent patient cohorts comprising the clinical entities PCNSL (n = 47), secondary central nervous system lymphomas (SCNSL; n = 13), multiple sclerosis (MS, n = 23), glioma (n = 10), other tumors (n = 17) and tumor-free controls (n = 21) by proteomic approaches. In total, we identified more than 1220 proteins in the cerebrospinal fluid (CSF) and validated eight candidate biomarkers by a peptide-centric approach in an independent patient cohort (n = 63). Thus, we obtained excellent diagnostic accuracy for the stratification between PCNSL, MS and glioma patients as well as tumor-free controls for three peptides originating from the three proteins VSIG4, GPNMB4 and APOC2. The combination of all three biomarker candidates resulted in diagnostic accuracy with an area under the curve (AUC) of 0.901 (PCNSL vs. MS), AUC of 0.953 (PCNSL vs. glioma) and AUC 0.850 (PCNSL vs. tumor-free control). In summary, the determination of VSIG4, GPNMB4 and APOC2 in CSF as novel biomarkers for supporting the diagnosis of PCNSL is suggested.

Intraoperative Flow Cytometry Enables the Differentiation of Primary Central Nervous System Lymphoma from Glioblastoma

2018 ◽  
Vol 112 ◽  
pp. e261-e268 ◽  
Author(s):  
Shunichi Koriyama ◽  
Masayuki Nitta ◽  
Takahiro Shioyama ◽  
Takashi Komori ◽  
Takashi Maruyama ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Central Nervous System Lymphoma

scholarly journals The role of surgical resection in primary central nervous system lymphoma: a single-center retrospective analysis of 70 patients

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shiqiang Wu ◽  
Junwen Wang ◽  
Weihua Liu ◽  
Feng Hu ◽  
Kai Zhao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Prognostic Factors ◽  
Surgical Resection ◽  
Stereotactic Biopsy ◽  
Multivariable Analysis ◽  
Central Nervous System Lymphoma ◽  
Brain Biopsy ◽  
Resection Group ◽  
Selection For

Abstract Background The aim of this study was to evaluate the effect of surgical resection and stereotactic biopsy on the complication rate, progression-free survival (PFS) and overall survival (OS) of 70 patients diagnosed at a single institution with primary central nervous system lymphoma (PCNSL) and to explore the predictors of selection for resection and the prognostic factors of PCNSL. Methods A retrospective analysis was performed of 70 patients with PCNSL that was diagnosed by surgical resection or stereotactic brain biopsy in our department from January 2013 to May 2019. We divided the patients into two groups: a resection group (n = 28) and a stereotactic biopsy group (n = 42). Data on clinical characteristics, imaging findings, complication rates, PFS and OS were retrospectively reviewed and compared between these two groups. We also analysed the predictors of selection for resection and prognostic factors of PCNSL by multivariate analysis. Results The median age was 53.3 ± 14.3 years, and there was a male predominance with a sex ratio of 1.33:1. The most common clinical manifestation was a headache. The complication rate in the resection group was 10.7% versus 7.1% in the stereotactic biopsy group, and there was no statistically significant difference. The rate of improvement in symptoms of the resection group was significantly higher than that of the stereotactic biopsy group. Multivariable analysis identified a single tumour and not involving deep structures as predictors of selection for resection. With a median follow-up of 30 months (range 1–110), the mean OS and PFS of all patients were 16.1 months and 6.2 months, respectively. Patients who underwent surgical resection had a mean OS of 23.4 months and PFS of 8.6 months versus 11.2 months and 4.6 months for those who had a brain biopsy performed. In addition, multivariable analysis showed that not involving deep structures and resection were favourable prognostic factors for PCNSL. Conclusions The outcomes of patients with PCNSL treated in our cohort are still poor. In our series, surgical resection might play a role in significantly improving OS and PFS compared with stereotactic biopsy in a subset of patients. The type of surgery and tumour location are prognostic factors for PCNSL.

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