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

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.

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Differentiating glioblastoma multiforme from cerebral lymphoma: application of advanced texture analysis of quantitative apparent diffusion coefficients

The Neuroradiology Journal ◽

10.1177/1971400920937382 ◽

2020 ◽

Vol 33 (5) ◽

pp. 428-436

Author(s):

Mehrsad Mehrnahad ◽

Sara Rostami ◽

Farnaz Kimia ◽

Reza Kord ◽

Morteza Sanei Taheri ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Diffusion Coefficient ◽

Glioblastoma Multiforme ◽

Apparent Diffusion Coefficient ◽

Central Nervous System Lymphoma ◽

Second Order ◽

Regions Of Interest ◽

Apparent Diffusion ◽

Histogram Feature

Purpose The purpose of this study was to differentiate glioblastoma multiforme from primary central nervous system lymphoma using the customised first and second-order histogram features derived from apparent diffusion coefficients. Methods and materials: A total of 82 patients (57 with glioblastoma multiforme and 25 with primary central nervous system lymphoma) were included in this study. The axial T1 post-contrast and fluid-attenuated inversion recovery magnetic resonance images were used to delineate regions of interest for the tumour and peritumoral oedema. The regions of interest were then co-registered with the apparent diffusion coefficient maps, and the first and second-order histogram features were extracted and compared between glioblastoma multiforme and primary central nervous system lymphoma groups. Receiver operating characteristic curve analysis was performed to calculate a cut-off value and its sensitivity and specificity to differentiate glioblastoma multiforme from primary central nervous system lymphoma. Results Based on the tumour regions of interest, apparent diffusion coefficient mean, maximum, median, uniformity and entropy were higher in the glioblastoma multiforme group than the primary central nervous system lymphoma group ( P ≤ 0.001). The most sensitive first and second-order histogram feature to differentiate glioblastoma multiforme from primary central nervous system lymphoma was the maximum of 2.026 or less (95% confidence interval (CI) 75.1–99.9%), and the most specific first and second-order histogram feature was smoothness of 1.28 or greater (84.0% CI 70.9–92.8%). Based on the oedema regions of interest, most of the first and second-order histogram features were higher in the glioblastoma multiforme group compared to the primary central nervous system lymphoma group ( P ≤ 0.015). The most sensitive first and second-order histogram feature to differentiate glioblastoma multiforme from primary central nervous system lymphoma was the 25th percentile of 0.675 or less (100% CI 83.2–100%) and the most specific first and second-order histogram feature was the median of 1.28 or less (85.9% CI 66.3–95.8%). Conclusions Texture analysis using first and second-order histogram features derived from apparent diffusion coefficient maps may be helpful in differentiating glioblastoma multiforme from primary central nervous system lymphoma.

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

Neuro-Oncology Practice ◽

10.1093/nop/npz015 ◽

2019 ◽

Vol 6 (6) ◽

pp. 415-423 ◽

Cited By ~ 1

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.

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

Neuro-Oncology ◽

10.1093/neuonc/noz126.284 ◽

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

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Diagnostic delay in primary central nervous system lymphoma

Acta Oncologica ◽

10.1080/02841860500256272 ◽

2005 ◽

Vol 44 (7) ◽

pp. 728-734 ◽

Cited By ~ 39

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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P17.02 Diagnostic delay and treatment options of Primary Central Nervous System Lymphoma in the last decade: preliminary results of first 50 patients from two Catalan institutions

Neuro-Oncology ◽

10.1093/neuonc/now188.276 ◽

2016 ◽

Vol 18 (suppl_4) ◽

pp. iv77-iv77

Author(s):

R. Velasco ◽

S. Mercadal ◽

N. Vidal ◽

A. López-Guillermo ◽

J. Bruna ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Treatment Options ◽

Diagnostic Delay ◽

Central Nervous System Lymphoma ◽

Preliminary Results

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Primary central nervous system lymphoma: is absence of intratumoral hemorrhage a characteristic finding on MRI?

Radiology and Oncology ◽

10.1515/raon-2015-0007 ◽

2015 ◽

Vol 49 (2) ◽

pp. 128-134 ◽

Cited By ~ 4

Author(s):

Akihiko Sakata ◽

Tomohisa Okada ◽

Akira Yamamoto ◽

Mitsunori Kanagaki ◽

Yasutaka Fushimi ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Glioblastoma Multiforme ◽

Central Nervous System Lymphoma ◽

Common Finding ◽

Inclusion Criteria ◽

Point Scale ◽

Characteristic Finding ◽

Intratumoral Hemorrhage ◽

Imaging Results

Abstract Background. Previous studies have shown that intratumoral hemorrhage is a common finding in glioblastoma multiforme, but is rarely observed in primary central nervous system lymphoma. Our aim was to reevaluate whether intratumoral hemorrhage observed on T2-weighted imaging (T2WI) as gross intratumoral hemorrhage and on susceptibilityweighted imaging as intratumoral susceptibility signal can differentiate primary central nervous system lymphoma from glioblastoma multiforme. Patients and methods. A retrospective cohort of brain tumors from August 2008 to March 2013 was searched, and 58 patients (19 with primary central nervous system lymphoma, 39 with glioblastoma multiforme) satisfied the inclusion criteria. Absence of gross intratumoral hemorrhage was examined on T2WI, and an intratumoral susceptibility signal was graded using a 3-point scale on susceptibility-weighted imaging. Results were compared between primary central nervous system lymphoma and glioblastoma multiforme, and values of P < 0.05 were considered significant. Results. Gross intratumoral hemorrhage on T2WI was absent in 15 patients (79%) with primary central nervous system lymphoma and 23 patients (59%) with glioblastoma multiforme. Absence of gross intratumoral hemorrhage could not differentiate between the two disorders (P = 0.20). However, intratumoral susceptibility signal grade 1 or 2 was diagnostic of primary central nervous system lymphoma with 78.9% sensitivity and 66.7% specificity (P < 0.001), irrespective of gross intratumoral hemorrhage. Conclusions. Low intratumoral susceptibility signal grades can differentiate primary central nervous system lymphoma from glioblastoma multiforme. However, specificity in this study was relatively low, and primary central nervous system lymphoma cannot be excluded based solely on the presence of an intratumoral susceptibility signal.

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P14.54 Primary central nervous system lymphoma of the spinal cord: a LOC network cohort study

Neuro-Oncology ◽

10.1093/neuonc/noab180.165 ◽

2021 ◽

Vol 23 (Supplement_2) ◽

pp. ii48-ii48

Author(s):

N Valyraki ◽

G Ahle ◽

E Tabouret ◽

R Houot ◽

F Jardin ◽

...

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Karnofsky Performance Status ◽

Performance Status ◽

Diagnostic Delay ◽

Central Nervous System Lymphoma ◽

High Dose ◽

Delay In Diagnosis ◽

The Brain

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) mainly affects the brain (>90% of the cases), Very little data can be found in the literature on PCNSL with spinal cord localization. MATERIAL AND METHODS We present a retrospective study based on the French LOC network database. We selected adult immunocompetentpatients, with a histological or cytological diagnosis of PCNSL, and a spinal cord localization at initial diagnosis. RESULTS Of the 2043 PCNSLof the LOC database newly diagnosed since 2011, 14 patients (9 men, median age 68, median Karnofsky performance status 50%)met the selection criteria. The median diagnostic delay was 82 days (min 15-max 1080) compared to 35 days in primary cerebral lymphomas. At diagnosis, walking was impossible in 7/14 patients and 5/14 had indwelling urinary catheter. On MRI, 100% had enlargement of the spinal cord with homogeneous contrast enhancement in 13/14 cases. Spinal cord lesions were unique in 9/14 patients and multiples in 5/14 patients. CSF IL10 level was increased in 6/7 patients. Brain lesions were found in 9/14 patients, located in the posterior fossa in 5/9 cases. The diagnosis was made either on a brain biopsy (N=6), a spinal cord biopsy or surgery (N=5) or the cytologic analysis of the CSF (N=3).4/5 patients had neurological sequel after spinal cord biopsy or surgery. All the patients were treated by high-dose methotrexate-based chemotherapy, followed by spinal cord irradiation (N=1) or autograft (N=2). There was an overall response rate of 71% (complete response in 8/14). 8/14 patients relapsed, 5 in the brain, 2 in the spinal cord, and 1 both in the spinal cord and in the brain. 2-year PFS and OS were 45% and 64%, respectively. Among the long-term responders, 50% remained in wheel chair, while only 10% could walk normally. CONCLUSION Considering the high risk of a spinal cord biopsy,the rarity of the disease, as well as the numerous differential diagnoses, the diagnosis of spinal cord lymphoma is difficult. Searching for other lymphomatous locations or assaying CSF IL10 may be helpful in this disease where delay in diagnosis is often prolonged et can cause irreversible handicap.

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