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 Influence of preoperative corticosteroid treatment on rate of diagnostic surgeries in primary central nervous system lymphoma: a multicenter retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Florian Scheichel ◽  
Franz Marhold ◽  
Daniel Pinggera ◽  
Barbara Kiesel ◽  
Tobias Rossmann ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retrospective Study ◽  
Diagnostic Delay ◽  
Central Nervous System Lymphoma ◽  
Corticosteroid Treatment ◽  
Histopathological Diagnosis ◽  
Significant Difference ◽  
The Difference ◽  
Immunocompetent Patients

Abstract Background Corticosteroid therapy (CST) prior to biopsy may hinder histopathological diagnosis in primary central nervous system lymphoma (PCNSL). Therefore, preoperative CST in patients with suspected PCNSL should be avoided if clinically possible. The aim of this study was thus to analyze the difference in the rate of diagnostic surgeries in PCNSL patients with and without preoperative CST. Methods A multicenter retrospective study including all immunocompetent patients diagnosed with PCNSL between 1/2004 and 9/2018 at four neurosurgical centers in Austria was conducted and the results were compared to literature. Results A total of 143 patients were included in this study. All patients showed visible contrast enhancement on preoperative MRI. There was no statistically significant difference in the rate of diagnostic surgeries with and without preoperative CST with 97.1% (68/70) and 97.3% (71/73), respectively (p = 1.0). Tapering and pause of CST did not influence the diagnostic rate. Including our study, there are 788 PCNSL patients described in literature with an odds ratio for inconclusive surgeries after CST of 3.3 (CI 1.7–6.4). Conclusions Preoperative CST should be avoided as it seems to diminish the diagnostic rate of biopsy in PCNSL patients. Yet, if CST has been administered preoperatively and there is still a contrast enhancing lesion to target for biopsy, surgeons should try to keep the diagnostic delay to a minimum as the likelihood for acquiring diagnostic tissue seems sufficiently high.

Primary leptomeningeal lymphoma masquerading as infectious tubercular meningitis

2021 ◽  
Vol 14 (9) ◽  
pp. e243574
Author(s):  
Salini Sumangala ◽  
Thidar Htwe ◽  
Yousuf Ansari ◽  
Lidia Martinez- Alvarez
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Correct Diagnosis ◽  
Central Nervous System Lymphoma ◽  
Final Diagnosis ◽  
Csf Analysis ◽  
Antitubercular Treatment ◽  
Lymphoma Treatment ◽  
Work Up ◽  
Timely Treatment

Primary central nervous system lymphoma (PCNSL) is infrequent and often poses diagnostic conundrums due to its protean manifestations. We present the case of a South Asian young man presenting with raised intracranial pressure and a lymphocytic cerebrospinal fluid (CSF) with pronounced hypoglycorrhachia. Progression of the neuro-ophthalmic signs while on early stages of antitubercular treatment led to additional investigations that produced a final diagnosis of primary leptomeningeal lymphoma. Treatment with chemoimmunotherapy (methotrexate, cytarabine, thiotepa and rituximab (MATRix)) achieved full radiological remission followed by successful autologous transplant. This case highlights the difficulties and diagnostic dilemmas when PCNSL presents as a chronic meningeal infiltrative process. While contextually this CSF is most often indicative of central nervous system tuberculosis and justifies empirical treatment initiation alone, it is essential to include differential diagnoses in the investigation work-up, which also carry poor prognosis without timely treatment. High suspicion, multidisciplinary collaboration and appropriate CSF analysis were the key for a correct diagnosis.

scholarly journals Diagnosis of primary central nervous system lymphoma: a systematic review of the utility of CSF screening and the role of early brain biopsy

2019 ◽  
Vol 6 (6) ◽  
pp. 415-423 ◽  
Author(s):  
Alexis A Morell ◽  
Ashish H Shah ◽  
Claudio Cavallo ◽  
Daniel G Eichberg ◽  
Christopher A Sarkiss ◽  
...  
Keyword(s):  
Systematic Review ◽  
Central Nervous System ◽  
Nervous System ◽  
Diagnostic Yield ◽  
Diagnostic Delay ◽  
Central Nervous System Lymphoma ◽  
Brain Biopsy ◽  
Suspected Case ◽  
Stereotactic Brain Biopsy

Abstract Background Because less-invasive techniques can obviate the need for brain biopsy in the diagnosis of primary central nervous system lymphoma (PCNSL), it is common practice to wait for a thorough initial work-up, which may delay treatment. We conducted a systematic review and reviewed our own series of patients to define the role of LP and early brain biopsy in the diagnosis of PCNSL. Methods Our study was divided into 2 main sections: 1) systematic review assessing the sensitivity of cerebrospinal fluid (CSF) analysis on the diagnosis of PCNSL, and 2) a retrospective, single-center patient series assessing the diagnostic accuracy and safety of early biopsy in immunocompetent PCNSL patients treated at our institution from 2012 to 2018. Results Our systematic review identified 1481 patients with PCNSL. A preoperative LP obviated surgery in 7.4% of cases. Brain biopsy was the preferred method of diagnosis in 95% of patients followed by CSF (3.1%). In our institutional series, brain biopsy was diagnostic in 92.3% of cases (24/26) with 2 cases that required a second procedure for diagnosis. Perioperative morbidity was noted in 7.6% of cases (n = 2) due to hemorrhages after stereotactic brain biopsy that improved at follow-up. Conclusions The diagnostic yield of CSF analyses for PCNSL in immunocompetent patients remains exceedingly low. Our institutional series demonstrates that early biopsy for PCNSL is safe and accurate, and may avert protracted work-ups. We conclude that performing an early brain biopsy in a suspected case of PCNSL is a valid, safe option to minimize diagnostic delay.

scholarly journals Multi-modality Therapy Leads to Longer Survival in Primary Central Nervous System Lymphoma Patients

2002 ◽  
Vol 29 (2) ◽  
pp. 147-153 ◽  
Author(s):  
Dhruv Singhal ◽  
Timothy F. Witham ◽  
Anand Germanwala ◽  
John C. Flickinger ◽  
David Schiff ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Radiation Therapy ◽  
Median Survival ◽  
Survival Data ◽  
Cox Regression ◽  
Central Nervous System Lymphoma ◽  
Treatment Modalities ◽  
Cox Regression Analysis ◽  
Single Modality

Abstract:Background:Primary central nervous system lymphoma (PCL) is more frequently encountered by neurosurgeons given the increasing incidence among both nonimmunocompromised and immunocompromised patients. The most frequent surgery is stereotactic biopsy. Historically, radiation therapy has been the standard treatment modality for this disease and median survival was in the 15-month range. More recently, multi-modality therapy combining radiation therapy with chemotherapy (systemic, intrathecal, and/or intra-arterial) have resulted in longer survivals. We reviewed survival data for our series of patients treated for PCL over the last decade.Methods:Thirty-four patients with histologically confirmed PCL were treated at our center. Multivariate Cox regression analysis was performed to determine which factor(s) (age, gender, HIV status, Karnofsky Performance Scale, chemotherapy, single modality therapy, histology, location, number of lesions, surgical resection) had a significant impact on survival.Results:The overall median survival was 19 months. Patients receiving multi-modality therapy (n=17) (chemotherapy and radiation) had a median survival of 34 months compared to four months for patients receiving single modality therapy (n=17 including seven HIV positive patients). Multi-modality therapy was the only significant factor affecting survival in this multivariate analysis (p<0.0001).Conclusions:Chemotherapy plus radiotherapy significantly enhances survival over patients treated with single modality therapy alone. Quality of life issues should be addressed on a case by case basis as additional treatment modalities are initiated.

Diagnostic delay and prognosis in primary central nervous system lymphoma compared with glioblastoma multiforme

2015 ◽  
Vol 37 (1) ◽  
pp. 23-29 ◽  
Author(s):  
R. Cerqua ◽  
S. Balestrini ◽  
C. Perozzi ◽  
V. Cameriere ◽  
S. Renzi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glioblastoma Multiforme ◽  
Diagnostic Delay ◽  
Central Nervous System Lymphoma

Whole Brain Radiation Alone Brings the Favorable Outcomes for AIDS Related Primary Central Nervous System Lymphoma (PCNSL) Especially with Good Performance Status in the HAART Era.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4751-4751
Author(s):  
Hirokazu Nagai ◽  
Takashi Odawara ◽  
Atsushi Ajisawa ◽  
Shotaro Hagiwara ◽  
Tomoko Uehira ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
Treatment Modalities ◽  
Combined Modality Treatment ◽  
Imaging Features ◽  
Whole Brain ◽  
Cox Regression Analysis ◽  
Radiotherapy Alone

Abstract Abstract 4751 Background Primary central nervous system lymphoma (PCNSL) is one of an acquired immunodeficiency syndrome (AIDS)-defining illness and is the second common cerebral mass lesion after toxoplasmosis in HIV infected population. The introduction of highly active antiretroviral therapy (HAART) significantly improved the survival of AIDS related PCNSL. But, the standard procedure to manage these patients still remains to be established. We performed the nationwide retrospective survey to elucidate the actual status and the significant prognostic variables of AIDS-related PCNSL in the HAART era. Methods All AIDS related PCNSL newly diagnosed at 12 regional center hospitals for HIV/AIDS in Japan during the period 2002-2008 were registered. The data about diagnostic modalities, CD4 counts, performance status (PS), HAART regimens, treatment modalities, and clinical outcomes were collected. A multivariate and univariate Cox regression analysis was performed to assess the effects of treatment and the clinical variables on OS. Results Twenty four AIDS related PCNSLs were registered. Median age was 41 (21-60) year old, and male gender was 96%. Ten patients were diagnosed as PCNSL based on imaging features and positive EBV DNA PCR of cerebrospinal fluid without brain biopsy. HAART was administrated in 88%. Twenty two patients were treated by radiotherapy alone, and only one cases were received the combined modality treatment. Multivariate analysis revealed that the significant predictor of improved survival was completion of whole brain radiotherapy (WBRT) with a total dosage more than 30 Gy (P=0.017). Furthermore, 9 of 10 patients with good PS (0-2) group were alive with CR (all were received WBRT), nevertheless 64% of poor PS (3 or 4) group (9/14) died sometimes with short clinical course. The estimated 3yrs overall survival rate of each group was 100% and 38% respectively (p=0.0198). The incidence and grade of radiation related leukoencephalopathy was limited in good PS group. Conclusion Radiotherapy alone with HAART is shown to be the most common treatment for the AIDS-related PCNSLs, but the role of systemic chemotherapy should be elucidated. Some AIDS-related PCNSLs, especially with good PS, achieved the durable remission by WBRT with the curative intent dose, in the HAART era. Disclosures: No relevant conflicts of interest to declare.

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

scholarly journals Diagnostic delay in primary central nervous system lymphoma

2005 ◽  
Vol 44 (7) ◽  
pp. 728-734 ◽  
Author(s):  
Ingfrid S. Haldorsen ◽  
Ansgar Espeland ◽  
John Ludvig Larsen ◽  
Olav Mella
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Diagnostic Delay ◽  
Central Nervous System Lymphoma
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