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 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.

scholarly journals Cerebrospinal fluid flow cytometry: utility in central nervous system lymphoma diagnosis

2021 ◽  
Vol 48 (s1) ◽  
pp. S2-S3
Author(s):  
KLK 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 ◽  
Cns Lymphoma ◽  
List Type ◽  
Csf Flow ◽  
Testing Algorithm

Flow cytometry of the cerebrospinal fluid (CSF) is used in isolation or as an adjunct to cytology to increase the sensitivity of detecting primary central nervous system (CNS) lymphoma. We aim to evaluate the sensitivity of CSF flow cytometry as a diagnostic tool for primary CNS lymphoma in patients presenting with undifferentiated neurologic symptoms. We retrospectively reviewed all CSF samples received by the Calgary Laboratory Services Flow Cytometry Laboratory 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. 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 69.4%. 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). CSF flow cytometry was negative in all patients who did not have a previous hematological malignancy or abnormal enhancement on MRI (n = 247). CSF flow cytometry has a limited role in screening for primary CNS lymphoma, unless a strictly endorsed testing algorithm is applied. It is, however, an invaluable tool in evaluating CNS involvement in patients with a previous diagnosis of hematolymphoid malignancy or abnormal enhancement on MRI.LEARNING OBJECTIVESThis presentation will enable the learner to:Discuss the costs and benefits of using CSF flow cytometry to diagnose CNS lymphoma 1.Identify appropriate clinical indications for using CSF flow cytometry as a first-line test2.Apply a testing algorithm to increase the diagnostic yield of CSF flow cytometry

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.

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.

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.

NIMG-69. FREQUENCY OF TUMOR-RELATED VASCULATURE IN PRIMARY CNS LYMPHOMA ON ROUTINE MRI

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi145-vi145
Author(s):  
Trusha Shah ◽  
Alipi Bonm ◽  
Jerome Graber
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
Clinical Database ◽  
Diffusion Restriction ◽  
Independent Reviewer ◽  
The University ◽  
And Diffusion

Abstract Primary central nervous system lymphoma (PCNSL) is known to express angiogenic factors and can have spontaneous or biopsy-related hemorrhage. Radiographically, PCNSL is characterized by homogenous enhancement and diffusion restriction, as well as T2/FLAIR abnormalities. A higher frequency of tumor-related vessels has been reported in gliomas compared to brain metastases, but this has not been assessed in PCNSL. We used a clinical database of patients with PCNSL treated at the University of Washington and reviewed pretreatment MRIs for 48 patients treated between 2014-2021 for whom susceptibility sequences were available. Median age at diagnosis was 64 years (range 35-90 years). Patients were 27.1% male and 72.9% female. Each lesion was scored by at least two independent reviewers for the presence of a prominent vessel located either centrally or eccentrically, and for the presence of hemorrhage. Lesions that were scored differently by the two reviewers (n=26) were then scored by a third independent reviewer. In several cases the findings were felt to be indeterminate. Lesions were considered measurable if they were greater than 5 mm in two perpendicular planes, and a total of 93 measurable lesions were categorized. Prominent vessels were seen in 56/93 (60.2%) lesions, with 26/56 (46.4%) being central and 30/56 (55.4%) being eccentric. An additional 7/93 (7.5%) lesions were indeterminate. Hemorrhage was seen in 11/93 (11.8%) lesions. We conclude that prominent vessels can be seen in a majority of PCNSL lesions on standard MRI.

scholarly journals Case-based review: primary central nervous system lymphoma

2017 ◽  
Vol 4 (1) ◽  
pp. 46-59 ◽  
Author(s):  
Agnieszka Korfel ◽  
Uwe Schlegel ◽  
Derek R. Johnson ◽  
Timothy J. Kaufmann ◽  
Caterina Giannini ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
Cns Lymphoma ◽  
High Dose ◽  
Tumor Biopsy

Abstract Primary CNS lymphoma (PCNSL) is a rare diffuse large B-cell lymphoma originating within the central nervous system. The overall incidence of PCNSL is rising, particularly in the elderly population. Immunosuppression is a strong risk factor, but most patients with this tumor are apparently immunocompetent. Diagnosis of PCNSL can be challenging. Non-invasive or minimally invasive tests such as ophthalmological evaluation and spinal fluid analysis may be useful, but the majority of patients require tumor biopsy for definitive diagnosis. Our knowledge concerning optimum treatment of PCNSL is fragmentary due to paucity of adequately sized trials. Most patients are now initially treated with high-dose-methotrexate-based chemotherapy alone, as the addition of whole-brain radiotherapy at standard doses has not been shown to increase survival and does increase the risk of neurological toxicity. Ongoing trials are addressing issues such as the roles of reduced-dose radiotherapy, the addition of the CD20 antibody rituximab to chemotherapy, high-dose chemotherapy followed by autologous stem cell transplantation, and maintenance therapy in the primary management of PCNSL.

scholarly journals Molecular pathogenesis of primary central nervous system lymphoma

2006 ◽  
Vol 21 (5) ◽  
pp. 1-5 ◽  
Author(s):  
Cigall Kadoch ◽  
Patrick Treseler ◽  
James L. Rubenstein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Current Knowledge ◽  
Profile Analysis ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Molecular Pathogenesis ◽  
Prognostic Biomarkers ◽  
Cns Lymphoma ◽  
Non Hodgkin Lymphoma

✓ Primary central nervous system lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma (NHL) typically associated with a worse prognosis than other localized extranodal lymphomas with similar histological characteristics. The defining feature of PCNSL is its confinement to the central nervous system (CNS), with proclivity for growth within the leptomeningeal as well as intraocular compartments. Primary CNS lymphoma rarely disseminates outside the CNS and accounts for less than 5% of all primary brain neoplasms. At least 95% of PCNSLs are of large B-cell histology, the most common subtype of NHL. Consistent with the trend seen in systemic NHLs, the incidence of PCNSL has markedly increased over the past three decades, both in immunocompromised and immunocompetent patients. Because PCNSL is relatively rare, the identification of molecular prognostic biomarkers and the definition of a standard therapeutic strategy have been challenging. The authors discuss the current knowledge of the molecular pathogenesis of CNS lymphomas and review the recent advances in gene expression profile analysis and identification of novel prognostic biomarkers.

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 Improving the antitumor activity of R-CHOP with NGR-hTNF in primary CNS lymphoma: final results of a phase 2 trial

2020 ◽  
Vol 4 (15) ◽  
pp. 3648-3658
Author(s):  
Andrés J. M. Ferreri ◽  
Teresa Calimeri ◽  
Maurilio Ponzoni ◽  
Flavio Curnis ◽  
Gian Marco Conte ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Cns Lymphoma ◽  
Human Tumor ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Phase 2 ◽  
Phase 2 Trial

Abstract Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment of diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system (CNS) (primary central nervous system lymphoma [PCNSL]) is an exception because of the low CNS bioavailability of related drugs. NGR–human tumor necrosis factor (NGR-hTNF) targets CD13+ vessels, enhances vascular permeability and CNS access of anticancer drugs, and provides the rationale for the treatment of PCNSL with R-CHOP. Herein, we report activity and safety of R-CHOP preceded by NGR-hTNF in patients with PCNSL relapsed/refractory to high-dose methotrexate-based chemotherapy enrolled in a phase 2 trial. Overall response rate (ORR) was the primary endpoint. A sample size of 28 patients was considered necessary to demonstrate improvement from 30% to 50% ORR. NGR-hTNF/R-CHOP would be declared active if ≥12 responses were recorded. Treatment was well tolerated; there were no cases of unexpected toxicities, dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with confirmed tumor response in 21 patients (75%; 95% confidence interval, 59%-91%), which was complete in 11. Seventeen of the 21 patients with response to treatment received consolidation (ASCT, WBRT, and/or lenalidomide maintenance). At a median follow-up of 21 (range, 14-31) months, 5 patients remained relapse-free and 6 were alive. The activity of NGR-hTNF/R-CHOP is in line with the expression of CD13 in both pericytes and endothelial cells of tumor vessels. High plasma levels of chromogranin A, an NGR-hTNF inhibitor, were associated with proton pump inhibitor use and a lower remission rate, suggesting that these drugs should be avoided during TNF-based therapy. Further research on this innovative approach to CNS lymphomas is warranted. The trial was registered as EudraCT: 2014-001532-11.

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