Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 45
Filter
1.
BMC Cancer ; 21(1): 183, 2021 Feb 22.
Article in English | MEDLINE | ID: mdl-33618687

ABSTRACT

BACKGROUD: Establishing diagnostic and prognostic biomarkers of primary central nervous system lymphoma (PCNSL) is a challenge. This study evaluated the value of dynamic interleukin (IL)-10 cerebrospinal fluid (CSF) concentrations for prognosis and relapse prediction in PCNSL. METHODS: Consecutive 40 patients newly diagnosed with PCNSL between April 2015 and April 2019 were recruited, and serial CSF specimens were collected by lumbar punctures (LP) or by Ommaya reservoir at diagnosis, treatment, and follow-up phase. RESULTS: We confirmed that an elevated IL-10 cutoff value of 8.2 pg/mL for the diagnosis value of PCNSL showed a sensitivity of 85%. A persistent detectable CSF IL-10 level at the end of treatment was associated with poor progression-free survival (PFS) (836 vs. 481 days, p = 0.049). Within a median follow-up of 13.6 (2-55) months, 24 patients relapsed. IL-10 relapse was defined as a positive conversion in patients with undetectable IL-10 or an increased concentration compared to the last test in patients with sustained IL-10. IL-10 relapse was detected a median of 67 days (28-402 days) earlier than disease relapse in 10/16 patients. CONCLUSION: This study highlights a new perspective that CSF IL-10 relapse could be a surrogate marker for disease relapse and detected earlier than conventional magnetic resonance imaging (MRI) scan. Further evaluation of IL-10 monitoring in PCNSL follow-up is warranted.


Subject(s)
Central Nervous System Neoplasms/cerebrospinal fluid , Interleukin-10/cerebrospinal fluid , Lymphoma, B-Cell/cerebrospinal fluid , Neoplasm Recurrence, Local/cerebrospinal fluid , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/cerebrospinal fluid , Central Nervous System Neoplasms/diagnostic imaging , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/pathology , Female , Humans , Lymphoma, B-Cell/diagnostic imaging , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/pathology , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Prognosis , Survival Rate
2.
J Clin Neurosci ; 81: 72-75, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33222973

ABSTRACT

We evaluated the cerebrospinal fluid (CSF) levels of the B-cell activating factor of the tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) in two cases of primary central nervous system B-cell lymphoma (PCNSBL) before and after treatment. One patient achieved clinical remission, and demonstrated decrease in the CSF levels of both BAFF and APRIL after treatment. Meanwhile, the other patient with insufficient therapeutic response showed increase in the BAFF levels despite decrease in APRIL levels. This report suggests that the combination of BAFF and APRIL levels could be useful in estimating the therapeutic efficacy in treating PCNSBL as reliable CSF markers.


Subject(s)
B-Cell Activating Factor/cerebrospinal fluid , Biomarkers, Tumor/cerebrospinal fluid , Brain Neoplasms/cerebrospinal fluid , Lymphoma, B-Cell/cerebrospinal fluid , Spinal Neoplasms/cerebrospinal fluid , Tumor Necrosis Factor Ligand Superfamily Member 13/cerebrospinal fluid , Aged , Antineoplastic Agents/administration & dosage , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/drug therapy , Cauda Equina/diagnostic imaging , Female , Humans , Male , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/drug therapy , Treatment Outcome
3.
Medicina (Kaunas) ; 56(6)2020 Jun 18.
Article in English | MEDLINE | ID: mdl-32570722

ABSTRACT

Background and Objectives: The injury burden after head trauma is exacerbated by secondary sequelae, which leads to further neuronal loss. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic protein and a key modulator of the programmed cell death (PCD) pathways. The current study evaluates the clinical evidence on Bcl-2 and neurological recovery in patients after traumatic brain injury (TBI). Materials and Methods: All studies in English were queried from the National Library of Medicine PubMed database using the following search terms: (B-cell lymphoma 2/Bcl-2/Bcl2) AND (brain injury/head injury/head trauma/traumatic brain injury) AND (human/patient/subject). There were 10 investigations conducted on Bcl-2 and apoptosis in TBI patients, of which 5 analyzed the pericontutional brain tissue obtained from surgical decompression, 4 studied Bcl-2 expression as a biomarker in the cerebrospinal fluid (CSF), and 1 was a prospective randomized trial. Results: Immunohistochemistry (IHC) in 94 adults with severe TBI showed upregulation of Bcl-2 in the pericontusional tissue. Bcl-2 was detected in 36-75% of TBI patients, while it was generally absent in the non-TBI controls, with Bcl-2 expression increased 2.9- to 17-fold in TBI patients. Terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick-end labeling (TUNEL) positivity for cell death was detected in 33-73% of TBI patients. CSF analysis in 113 TBI subjects (90 adults, 23 pediatric patients) showed upregulation of Bcl-2 that peaked on post-injury day 3 and subsequently declined after day 5. Increased Bcl-2 in the peritraumatic tissue, rising CSF Bcl-2 levels, and the variant allele of rs17759659 are associated with improved mortality and better outcomes on the Glasgow Outcome Score (GOS). Conclusions: Bcl-2 is upregulated in the pericontusional brain and CSF in the acute period after TBI. Bcl-2 has a neuroprotective role as a pro-survival protein in experimental models, and increased expression in patients can contribute to improvement in clinical outcomes. Its utility as a biomarker and therapeutic target to block neuronal apoptosis after TBI warrants further evaluation.


Subject(s)
Apoptosis/physiology , Brain Injuries, Traumatic/complications , Lymphoma, B-Cell/cerebrospinal fluid , Biomarkers/analysis , Biomarkers/cerebrospinal fluid , Brain Injuries, Traumatic/cerebrospinal fluid , Brain Injuries, Traumatic/physiopathology , Humans , Lymphoma, B-Cell/physiopathology , Proto-Oncogene Proteins c-bcl-2/analysis , Proto-Oncogene Proteins c-bcl-2/cerebrospinal fluid
5.
Hematol Oncol ; 36(2): 429-435, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29210102

ABSTRACT

The gold standard for diagnosis of central nervous system lymphomas still regards a stereotactic brain biopsy, with the risk of major complications for the patient. As tumor cells can be detected in cerebrospinal fluid (CSF), CSF analysis can be used as an alternative. In this respect, mutation analysis in CSF can be of added value to other diagnostic parameters such a cytomorphology and clonality analysis. A well-known example of targeted mutation analysis entails MYD88 p.(L265P) detection, which is present in the majority of Bing Neel syndrome and primary central nervous system lymphoma (PCNSL) patients. Unfortunately, tumor yield in CSF can be very low. Therefore, use of the highly sensitive droplet digital PCR (ddPCR) might be a suitable analysis strategy for targeted mutation detection. We analyzed 26 formalin fixed paraffin embedded (FFPE) samples (8 positive and 18 negative for MYD88 p.(L265P) mutation) by ddPCR, of which the results were compared with next generation sequencing (NGS). Subsequently, 32 CSF samples were analyzed by ddPCR. ddPCR and NGS results on FFPE material showed 100% concordance. Among the 32 CSF samples, 9 belonged to patients with lymphoplasmacytic lymphoma (LPL) and clinical suspicion of Bing Neel syndrome, and 3 belonged to patients with PCNSL. Nine of these samples tested positive for MYD88 p.(L265P) (8 LPL and 1 PCNSL). This study shows that sensitive MYD88 mutation analysis by ddPCR in CSF is highly reliable and can be applied even when DNA input is low. Therefore, ddPCR is of added value to current diagnostic parameters, especially when the available amount of DNA is limited.


Subject(s)
DNA Mutational Analysis/methods , Mutation , Myeloid Differentiation Factor 88/genetics , Polymerase Chain Reaction/methods , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/genetics , Humans , Liquid Biopsy , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/genetics , Reproducibility of Results , Sensitivity and Specificity , Waldenstrom Macroglobulinemia/cerebrospinal fluid , Waldenstrom Macroglobulinemia/diagnosis , Waldenstrom Macroglobulinemia/genetics
6.
Cancer Discov ; 7(9): 1018-1029, 2017 09.
Article in English | MEDLINE | ID: mdl-28619981

ABSTRACT

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with NF-κB. The role of BTK in primary central nervous system (CNS) lymphoma (PCNSL) is unknown. We performed a phase I clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS lymphoma. Clinical responses to ibrutinib occurred in 10 of 13 (77%) patients with PCNSL, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of CARD11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-cell antigen receptor-associated protein CD79B. CD79B-mutant PCNSLs showed enrichment of mammalian target of rapamycin (mTOR)-related gene sets and increased staining with PI3K/mTOR activation markers. Inhibition of the PI3K isoforms p110α/p110δ or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells.Significance: Ibrutinib has substantial activity in patients with relapsed or refractory B-cell lymphoma of the CNS. Response rates in PCNSL were considerably higher than reported for diffuse large B-cell lymphoma outside the CNS, suggesting a divergent molecular pathogenesis. Combined inhibition of BTK and PI3K/mTOR may augment the ibrutinib response in CD79B-mutant human PCNSLs. Cancer Discov; 7(9); 1018-29. ©2017 AACR.See related commentary by Lakshmanan and Byrd, p. 940This article is highlighted in the In This Issue feature, p. 920.


Subject(s)
Antineoplastic Agents/therapeutic use , Central Nervous System Neoplasms/drug therapy , Lymphoma, B-Cell/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Adenine/analogs & derivatives , Adult , Agammaglobulinaemia Tyrosine Kinase , Aged , Aged, 80 and over , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , CARD Signaling Adaptor Proteins/genetics , Central Nervous System Neoplasms/blood , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/metabolism , Drug Resistance, Neoplasm/genetics , Female , Guanylate Cyclase/genetics , Humans , Lymphoma, B-Cell/blood , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/metabolism , Male , Maximum Tolerated Dose , Middle Aged , Mutation , Piperidines , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacokinetics , Protein-Tyrosine Kinases/antagonists & inhibitors , Pyrazoles/adverse effects , Pyrazoles/pharmacokinetics , Pyrimidines/adverse effects , Pyrimidines/pharmacokinetics , Treatment Outcome , Young Adult
7.
J Clin Neurosci ; 35: 122-126, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27839915

ABSTRACT

Primary spinal intradural extramedullary lymphoma remains a very rare entity in spinal oncology. In this case report, we present the first treatment of a PSIEL diagnosed by cytopathologic analysis alone followed by urgent radio- and chemotherapy in the literature. At 18-month follow-up, our patient was ambulatory with near total imaging resolution of the lesion. In conclusion, surgical excision or biopsy may not be necessary when suspicion for PSIEL exists, and may delay prompt medical and radiation treatment due to necessity for wound healing. Further research into the management of extramedullary lymphoma treatment strategies is warranted.


Subject(s)
Chemoradiotherapy/methods , Lymphoma, B-Cell/therapy , Spinal Cord Neoplasms/therapy , Aged , Female , Humans , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/diagnostic imaging , Magnetic Resonance Imaging , Spinal Cord Compression/etiology , Spinal Cord Neoplasms/cerebrospinal fluid , Spinal Cord Neoplasms/diagnostic imaging , Spinal Puncture
8.
Sci Rep ; 6: 38671, 2016 12 07.
Article in English | MEDLINE | ID: mdl-27924864

ABSTRACT

Early diagnosis of primary central nervous system lymphoma (PCNSL) represents a challenge, and cerebrospinal fluid (CSF) cytokines may be diagnostic biomarkers for PCNSL. We used an electrochemiluminescence immunoassay to measure interleukin (IL)-10, IL-6, IL-8 and tumor necrosis factor α (TNF-α) in the CSF of 22 B cell PCNSL patients and 80 patients with other CNS diseases. CSF IL-10 was significantly higher in PCNSL patients than in the control group (median 74.7 pg/ml vs < 5.0 pg/ml, P < 0.000). Using a CSF IL-10 cutoff value of 8.2 pg/ml, the diagnostic sensitivity and specificity were 95.5% and 96.1%, respectively (AUC, 0.957; 95% CI, 0.901-1.000). For a CSF IL-10/IL-6 cutoff value of 0.72, the sensitivity was 95.5%, and the specificity was 100.0% (AUC, 0.976; 95% CI, 0.929-1.000). An increased CSF IL-10 level at diagnosis and post-treatment was associated with poor Progression free survival (PFS) for patients with PCNSL (P = 0.0181 and P = 0.0002, respectively). A low diagnostic value for PCNSL was found with CSF IL-8 or TNF-α. In conclusion, increased CSF IL-10 was a reliable diagnostic biomarker for large B cell PCNSL, and an IL-10/IL-6 ratio facilitates differentiation from other conditions, especially a CNS infection.


Subject(s)
Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/diagnosis , Interleukin-10/cerebrospinal fluid , Interleukin-6/cerebrospinal fluid , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/diagnosis , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor , Central Nervous System Neoplasms/mortality , Central Nervous System Neoplasms/therapy , Cytokines/cerebrospinal fluid , Female , Humans , Lymphoma, B-Cell/mortality , Male , Middle Aged , Neoplasm Staging , Prognosis , ROC Curve , Survival Analysis , Treatment Outcome
9.
Hematol Oncol Clin North Am ; 30(6): 1277-1291, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27888881

ABSTRACT

Central nervous system (CNS) relapse of aggressive B-cell lymphoma is a rare but serious complication with poor survival. Different approaches have been used to define risks factors for CNS relapse and establish prophylactic measures. Although patients with low or intermediate risk of CNS relapse should not undergo special diagnostic or therapeutic measures, CNS MRI as well as cytology and flow cytometry of the cerebrospinal fluid are suggested for high-risk patients (and patients with testicular involvement) at diagnosis, and prophylactic high-dose methotrexate in patients without proven CNS involvement. Future risk and treatment models may include molecular features and new treatment options.


Subject(s)
Central Nervous System Neoplasms , Lymphoma, B-Cell , Magnetic Resonance Imaging/methods , Methotrexate/therapeutic use , Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/diagnostic imaging , Central Nervous System Neoplasms/prevention & control , Humans , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/diagnostic imaging , Lymphoma, B-Cell/prevention & control
10.
Intern Med ; 54(12): 1547-52, 2015.
Article in English | MEDLINE | ID: mdl-26073248

ABSTRACT

A 71-year-old immunocompetent man developed cognitive decline and gait disturbance. Brain magnetic resonance imaging (MRI) revealed bilateral diffuse leukoencephalopathy without a mass lesion. An analysis of the cerebrospinal fluid (CSF) showed elevated levels of interleukin (IL)-10. The condition of the patient progressively deteriorated, and intravenous high-dose steroids proved ineffective. Detection of non-destructive, diffusely infiltrating, large B-cell lymphoma in biopsy and autopsy specimens led to a diagnosis of lymphomatosis cerebri (LC). On serial MRI, the basal ganglia and white matter lesions increased in parallel with the levels of IL-10. These findings suggest that the IL-10 level in the CSF may represent a potentially useful biomarker for the early diagnosis and monitoring of the disease progression in LC.


Subject(s)
Biomarkers, Tumor/cerebrospinal fluid , Brain Neoplasms/cerebrospinal fluid , Cognition Disorders/cerebrospinal fluid , Gait Disorders, Neurologic/cerebrospinal fluid , Interleukin-10/cerebrospinal fluid , Lymphoma, B-Cell/cerebrospinal fluid , Aged , Autopsy , Biopsy , Brain Neoplasms/complications , Brain Neoplasms/pathology , Cognition Disorders/etiology , Disease Progression , Fatal Outcome , Gait Disorders, Neurologic/etiology , Humans , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/pathology , Magnetic Resonance Imaging , Male
11.
Ann Clin Biochem ; 52(Pt 1): 161-4, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25074990

ABSTRACT

We present two cases of spuriously high cerebrospinal fluid glucose concentration with approximately normal blood glucose concentrations. The cause of these abnormal findings was the use of inappropriate collection tubes during the pre-analytical phase. Whilst no patient harm was identified following this error, significant time and effort were expended by both laboratory and clinical staff to explain the cause of these findings.


Subject(s)
Artifacts , Glucose/cerebrospinal fluid , Lymphoma, B-Cell/cerebrospinal fluid , Specimen Handling/standards , Aged , Blood Glucose/metabolism , Disposable Equipment , Humans , Lymphoma, B-Cell/blood , Lymphoma, B-Cell/diagnosis , Lymphoma, B-Cell/pathology , Male , Middle Aged
12.
CNS Oncol ; 3(1): 77-85, 2014 Jan.
Article in English | MEDLINE | ID: mdl-25054902

ABSTRACT

CNS lymphomas represent rare and aggressive variants of extranodal non-Hodgkin's lymphomas, which may present with diverse neurological symptoms and are often diagnostically challenging. Primary CNS lymphomas develop within the CNS and characteristically involve the brain, leptomeninges, eyes and, in rare cases, spinal cord. Secondary CNS lymphomas are characterized by expansion of systemic lymphomas to the CNS. Multimodal investigation of cerebrospinal fluid (CSF) comprises an important component of the diagnostic work-up for patients with suspected CNS lymphomas. Cytopathological examination of the CSF is still regarded as the 'gold standard' for the diagnosis of leptomeningeal malignant disease. However, cytopathology has only a low sensitivity in detecting leptomeningeal lymphoma involvement. Modern technologies including proteochemical and immunophenotypic studies by flow cytometry, and molecular genetic analyses of CSF may increase sensitivity and specificity, therefore, facilitating the diagnosis of CNS lymphomas. This review gives an overview and discussion of the current aspects of CSF analyses in CNS lymphomas.


Subject(s)
Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/diagnosis , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/diagnosis , Central Nervous System Neoplasms/genetics , Humans , Lymphoma, B-Cell/genetics , Proteins/metabolism
14.
Brain Nerve ; 64(11): 1347-51, 2012 Nov.
Article in Japanese | MEDLINE | ID: mdl-23131747

ABSTRACT

We report a case of primary central nervous system lymphoma (PCNSL) that presented with visual disturbance. A 76-year-old man developed decreased bilateral visual acuity. He was diagnosed with bilateral retrobulbar neuritis by an ophthalmologist. Treatment with high-dose corticosteroids was initiated and resulted in mild improvement of visual acuity. However, the patient gradually became apathetic and bradykinetic, experiencing difficulty performing the activities of daily living; he was admitted to our hospital because of this progressive illness. Neurological examination revealed bradyphrenia and bradykinesia with frontal lobe release signs, disorientation, and ideomotor apraxia. Magnetic resonance imaging showed abnormal signals in the bilateral basal ganglia and thalamus. Cerebrospinal fluid (CSF) examination revealed no pleocytosis and slightly elevated protein levels: ß2-microglobulin level was mildly increased, and IL-10 level in the CSF was markedly elevated. These findings suggested a diagnosis of PCNSL, and a brain biopsy specimen was obtained from the left caudate head. Pathological findings indicated diffuse large B-cell lymphoma. Nonspecific neurological manifestations and radiological findings can make the diagnosis of PCNSL difficult and result in delayed diagnosis. Visual impairment has been suggested as a feature of PCNSL, and an elevated IL-10 level in the CSF may be a useful marker for diagnosing PCNSL.


Subject(s)
Central Nervous System Neoplasms/cerebrospinal fluid , Central Nervous System Neoplasms/pathology , Interleukin-10/cerebrospinal fluid , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/pathology , Aged , Biopsy , Brain/pathology , Central Nervous System Neoplasms/diagnosis , Humans , Lymphoma, B-Cell/diagnosis , Magnetic Resonance Imaging , Male
15.
Cytometry B Clin Cytom ; 82(3): 139-44, 2012 May.
Article in English | MEDLINE | ID: mdl-22328059

ABSTRACT

BACKGROUND: Flow cytometry (FC) is considered a sensitive and specific technique for the detection of occult lymphoma cells in cerebrospinal fluid (CSF). METHODS: The diagnostic sensitivity of a FC approach which uses a combination of 10 antibodies, a single-tube evaluation, and a six-color instrument, was evaluated and compared to conventional cytology (CC) for the detection of lymphomatous cells in the CSF of 44 patients affected by B-cell non-Hodgkin's lymphoma (B-NHL) considered at high risk of central nervous system spread. RESULTS: The CSF obtained from 36 newly diagnosed and 8 relapsed patients affected by B-cell lymphoma was assessed by FC and CC on a total of 62 samples; 52/62 (82.6%) were considered paucicellular as they had fewer than 10 cells/µl. All cases were evaluated by both methods. FC gave 15/62 (24%) positive results, CC 10/62 (16%) positive results; none of the samples evaluated had a positive CC with a negative FC result. CONCLUSIONS: The use of a multiparameter FC approach, which collects an elevated number of monoclonal antibodies in a single tube and identify different cell populations with a selective gating strategy analysis, allows for the evaluation of lymphocyte subsets and the detection of leptomeningeal disease in B-NHL, even in the presence of paucicellularity of samples.


Subject(s)
Cerebrospinal Fluid/cytology , Flow Cytometry , Lymphoma, B-Cell/cerebrospinal fluid , Meningeal Neoplasms/cerebrospinal fluid , Antibodies, Monoclonal , Female , Humans , Immunophenotyping , Male
16.
Antivir Ther ; 17(1): 125-8, 2012.
Article in English | MEDLINE | ID: mdl-22267477

ABSTRACT

Herpes simplex virus type 2 (HSV-2) can cause radiculo-myelitis as a neurological manifestation. We report a case of ongoing HSV-2 DNA positivity in the cerebrospinal fluid (CSF) of at least eight weeks under antiviral therapy with acyclovir in a highly immunocompromised hemato-oncologic patient with HSV-2-associated radiculitis. Upon admission, the patient presented with pain, leg paresis, and urinary incontinence, as well as pleocytosis in the CSF. Quantitative real-time PCR of the CSF at day 3 after admission revealed HSV-2 with a concentration of 2.0×10(5) copies/ml and treatment with acyclovir intravenously and prednisolone by mouth was started. Clinical symptoms resolved almost completely after approximately 3 weeks of antiviral therapy. However, CSF samples of day 12, 19, 26, 33, 39, 48 and 54 after admission showed a slow decline of HSV-2 DNA concentrations. HSV-2 DNA was still detectable (1.6×10(4) copies/ml) at day 54 after admission. Genotypic resistance testing showed, as far as available, no mutations indicative for acyclovir resistance. Since an increasing specific antibody index for HSV was observed, we speculate that the prolonged detectability of HSV-2 DNA in the CSF might not necessarily indicate ongoing viral replication but neutralized virus. Other hypotheses and the consequences on treatment are discussed. To our knowledge this is the first report about the long-term viral load kinetics of HSV-2 in the CSF of a patient with radiculitis under antiviral therapy, highlighting the need for further studies on HSV DNA kinetics in the CSF and their significance for an appropriate antiviral treatment.


Subject(s)
DNA, Viral/cerebrospinal fluid , Herpes Simplex/virology , Lymphoma, B-Cell/virology , Radiculopathy/virology , Acyclovir/administration & dosage , Acyclovir/therapeutic use , Aged , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , DNA Copy Number Variations , Female , Herpes Simplex/cerebrospinal fluid , Herpes Simplex/complications , Herpes Simplex/drug therapy , Herpesvirus 2, Human/genetics , Herpesvirus 2, Human/isolation & purification , Humans , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/complications , Lymphoma, B-Cell/drug therapy , Prednisolone/administration & dosage , Prednisolone/therapeutic use , Radiculopathy/cerebrospinal fluid , Radiculopathy/complications , Radiculopathy/drug therapy , Real-Time Polymerase Chain Reaction , Time Factors , Viral Load
17.
J Clin Neurosci ; 18(7): 978-80, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21565511

ABSTRACT

We report a patient diagnosed with a B-cell lymphoma after detecting monoclonal B-cells in the cerebrospinal fluid (CSF) and who had only minimal symptoms and a benign course. A 46-year-old man experienced three transitory episodes with neurological symptoms. On examination papilledema in both eyes was found. Flow cytometry (FACS)-analysis detected monoclonal B-cells in the CSF as well as in the peripheral blood and the bone marrow. Results were consistent with a low-risk lymphoma, most probably a marginal zone B-cell lymphoma. Interestingly, our patient had no progressive clinical symptoms and remained without specific therapy during 36 months of follow-up. Nevertheless, CSF-analysis led to the diagnosis of the B-cell lymphoma.


Subject(s)
Leukocytosis/cerebrospinal fluid , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/pathology , Anomia/etiology , Antihypertensive Agents/therapeutic use , Cell Separation , Dermatomyositis/pathology , Flow Cytometry , Headache/etiology , Humans , Hypertension/complications , Hypertension/drug therapy , Hypesthesia/etiology , Immunophenotyping , Lymphoma, B-Cell/complications , Male , Middle Aged , Muscle Weakness/etiology , Papilledema/etiology , Speech Disorders/etiology , Splenomegaly/pathology , Vision Disorders/etiology
18.
Neurol Sci ; 32(6): 1171-4, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21567181

ABSTRACT

Primary leptomeningeal lymphoma is a rare syndrome characterized by lymphomatous meningeal infiltration without identification of systemic lymphoma or parenchymal central nervous system lymphoma. We report a case of a 62-year-old immunocompetent woman with primary spinal leptomeningeal lymphoma presenting as cervical and lumbar radiculopathy who is rare because of particularly unusual onset site of B cell lymphoma. Interestingly, the diagnosis was possible only by cerebrospinal fluid flow cytometry.


Subject(s)
Lymphoma, B-Cell/complications , Meningeal Neoplasms/complications , Radiculopathy/diagnosis , Radiculopathy/etiology , Antigens, CD/metabolism , Cerebrospinal Fluid , Female , Flow Cytometry/methods , Humans , Immunocompetence , Lymphoma, B-Cell/cerebrospinal fluid , Meningeal Neoplasms/cerebrospinal fluid , Middle Aged
19.
Am J Clin Pathol ; 135(1): 22-34, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21173121

ABSTRACT

Flow cytometric immunophenotyping (FCI) is recommended in the evaluation of cerebrospinal fluid (CSF) specimens for hematologic neoplasms. This study reviewed FCI of CSF specimens collected for primary diagnosis (n = 77) and follow-up for known malignancy (n = 153). FCI was positive in 11 (4.8%) of 230 specimens: acute myeloid leukemia, 6; precursor B-acute lymphoblastic leukemia, 2; B-cell lymphoma, 2; and T-cell lymphoma, 1. Positive results were obtained in low-cellularity specimens, including 2 with fewer than 100 events in the population of interest. FCI was indeterminate in 19 (8.3%) of 230 specimens, including 3 with only sparse events, 8 with possible artifact (apparent lack of staining, nonspecific or background staining, and aspirated air), and 8 with phenotypic findings considered insufficient for diagnosis. Indeterminate specimens were often limited by low cellularity and lacked normal cell populations to evaluate for appropriate staining. FCI may be of value in low-cellularity CSF specimens, although the results should be interpreted with caution.


Subject(s)
Cerebrospinal Fluid/immunology , Flow Cytometry/methods , Immunophenotyping/methods , Leukemia, Myeloid, Acute/diagnosis , Lymphoma, B-Cell/diagnosis , Lymphoma, T-Cell/diagnosis , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Acute Disease , Humans , Leukemia, Myeloid, Acute/cerebrospinal fluid , Leukemia, Myeloid, Acute/immunology , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/immunology , Lymphoma, T-Cell/cerebrospinal fluid , Lymphoma, T-Cell/immunology , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/cerebrospinal fluid , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/immunology
20.
Clin Neuropathol ; 29(6): 378-83, 2010.
Article in English | MEDLINE | ID: mdl-21073842

ABSTRACT

Herein, we report the case of a 72-year-old male with an exceedingly rare manifestation of a low-grade lymphoma in the brain associated with light chain deposition disease (LCDD). The patient presented with epileptic seizures. Magnetic resonance imaging (MRI) of the brain revealed multiple hyperintense lesions in the right parietal lobe that were suspicious of vasculitis, low-grade glioma, or neurosarcoidosis. In the cerebrospinal fluid (CSF), but not in the serum, highly elevated IgG was found. A stereotactic biopsy of one cerebral lesion was performed. Histopathology revealed a low grade lymphoplasmacytic B-cell lymphoma with light chain deposition disease (LCDD). Bone marrow biopsy and laboratory workup did not show any systemic involvement. LCDD exclusively affecting the brain is an exceedingly rare finding. It can be associated with low-grade B-cell lymphoma. This is the first report of LCDD exclusively affecting the brain in an elderly patient. Compared with the two younger patients previously reported, the course of the disease was of a slow-evolving nature. In constellations of highly elevated IgG in CSF and multiple white matter lesions, LCDD should be considered as underlying pathology.


Subject(s)
Brain Diseases/diagnosis , Brain Diseases/immunology , Brain Neoplasms/diagnosis , Immunoglobulin G/cerebrospinal fluid , Immunoglobulin Light Chains/metabolism , Lymphoma, B-Cell/diagnosis , Lymphoma, Non-Hodgkin/diagnosis , Aged , Biomarkers/cerebrospinal fluid , Biopsy , Bone Marrow/pathology , Brain Diseases/cerebrospinal fluid , Brain Neoplasms/cerebrospinal fluid , Brain Neoplasms/pathology , Humans , Lymphoma, B-Cell/cerebrospinal fluid , Lymphoma, B-Cell/pathology , Lymphoma, Non-Hodgkin/cerebrospinal fluid , Lymphoma, Non-Hodgkin/pathology , Magnetic Resonance Imaging , Male
SELECTION OF CITATIONS
SEARCH DETAIL
...