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

Author(s):  
Ka Loong Kelvin Au ◽  
Sarah Latonas ◽  
Afshin Shameli ◽  
Iwona Auer ◽  
Christopher Hahn

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.

Author(s):  
KLK Au ◽  
S Latonas ◽  
A Shameli ◽  
I Auer ◽  
C Hahn

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


Author(s):  
K Au ◽  
S Latonas ◽  
A Shameli ◽  
I Auer ◽  
C Hahn

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.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1644-1644 ◽  
Author(s):  
Jean-Francois Larouche ◽  
Marc Bergeron ◽  
Grace Hampson ◽  
Tim Illidge ◽  
Robert Delage

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.


Author(s):  
Ramon F Barajas Jr ◽  
Letterio S Politi ◽  
Nicoletta Anzalone ◽  
Heiko Schöder ◽  
Christopher P Fox ◽  
...  

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.


2015 ◽  
Vol 59 (4) ◽  
pp. 339-344 ◽  
Author(s):  
Juan Xing ◽  
Lisa Radkay ◽  
Sara E. Monaco ◽  
Christine G. Roth ◽  
Liron Pantanowitz

Lyme disease can affect the central nervous system causing a B-cell-predominant lymphocytic pleocytosis. Since most reactions to infection in the cerebrospinal fluid (CSF) are typically T-cell predominant, a B-cell-predominant lymphocytosis raises concern for lymphoma. We present 3 Lyme neuroborreliosis cases in order to illustrate the challenging cytomorphological and immunophenotypic features of their CSF specimens. Three male patients who presented with central nervous system manifestations were diagnosed with Lyme disease. The clinical presentation, laboratory tests, CSF cytological examination and flow-cytometric studies were described for each case. CSF cytology showed lymphocytic pleocytosis with increased plasmacytoid cells and/or plasma cells. Flow cytometry showed the presence of polytypic B lymphocytes with evidence of plasmacytic differentiation in 2 cases. In all cases, Lyme disease was confirmed by the Lyme screening test and Western blotting. In such cases of Lyme neuroborreliosis, flow cytometry of CSF samples employing plasmacytic markers and cytoplasmic light-chain analysis is diagnostically helpful to exclude lymphoma.


2006 ◽  
Vol 21 (5) ◽  
pp. 1-7 ◽  
Author(s):  
Marc C. Chamberlain

✓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.


1998 ◽  
Vol 112 (5) ◽  
pp. 476-479 ◽  
Author(s):  
Shin Kariya ◽  
Kazunori Nishizaki ◽  
Katsuya Aoji ◽  
Hirofumi Akagi

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.


2021 ◽  
Author(s):  
Endre Sebestyén ◽  
Ákos Nagy ◽  
Dóra Marosvári ◽  
Hajnalka Rajnai ◽  
Béla Kajtár ◽  
...  

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.


Author(s):  
Joshua H. Smith ◽  
Jose Jaime García

The cerebrospinal fluid present in the central nervous system plays an important role in the physiological activities and protection of the brain. Disruptions of CSF flow lead to different forms of a disease known as hydrocephalus, characterized by a significant increment of the ventricular space. In acute hydrocephalus the Sylvius aqueduct is blocked and ventricular pressure is greatly increased.


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