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1.
Tumori ; 106(1): 12-24, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31452454

RESUMO

OBJECTIVE: This study reviews the scientific literature to identify and describe which assessment tools (ATs) are used in pediatric oncology and neuro-oncology rehabilitation and which development neuropsychomotor (DNPM) ATs were built for children with central nervous system (CNS) tumors. METHODS: A systematic review was performed searching PubMed, CINAHL, PEDro, Science Direct, and Catalog of National Institute of Tumors databases and specialized journals. The search covered 7 years (2010-2017) and used relevant keywords in different combinations. A further search was carried out on DNPM rehabilitation manuals and academic thesis. RESULTS: The review retrieved 35 eligible articles containing 63 ATs. The most common ATs were the Behavioral Rating Inventory of Executive Function (BRIEF) and the Wechsler Intelligence Scale for Children (WISC). Most of the ATs covered a single area of child development among behavioral/psychological, cognitive, and motor areas. A total of 159 ATs were found in manuals and thesis, and only 17 of them were already identified in the journal search. None of the ATs identified in both searches had been specifically developed for children with CNS tumor. CONCLUSION: The results highlight the need to develop and validate a global multidimensional AT for children with CNS tumor, overcoming the fragmentation of the assessment procedures and promoting standardized rehabilitation protocols.


Assuntos
Neoplasias do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/reabilitação , Reabilitação Neurológica , Testes Neuropsicológicos , Transtornos Psicomotores/etiologia , Transtornos Psicomotores/reabilitação , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Criança , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/terapia , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/terapia , Resultado do Tratamento
2.
Ann Hematol ; 99(1): 93-104, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31758262

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin's lymphoma and a limited number of cases have been reported from China. This study aimed to investigate the clinicopathological features of newly diagnosed PCNSLs from a single center in eastern China and to identify the potential prognostic factors for overall survival (OS) and progression-free survival (PFS). All consecutive patients with histopathologically diagnosed PCNSLs at our center between January 2003 and October 2017 were recruited. Demographic and clinicopathological data were collected and reviewed retrospectively. The potential risk factors for OS and PFS were identified using the log-rank test and Cox regression analysis. A total of 167 immunocompetent cases were enrolled. The median age was 58 years (range 17-96 years), and the male:female ratio was 3:2. Headache (n = 65; 39%) and cerebral hemisphere (n = 96; 57%) were the most common presenting complaint and location, respectively. Out of 167 cases, 150 cases were diffuse large B cell lymphomas. With a median follow-up of 25 months (range 1-152 ), the median OS and PFS were 37 months (95% CI, 25-49) and 17 months (95% CI, 13-20), respectively. Residual tumor after operation, chemotherapy without HD-MTX and palliative treatment was revealed as independent prognostic markers. Moreover, ECOG > 3, multifocal lesions, and palliative treatment were revealed as unfavorable independent prognostic markers for PFS. In conclusion, Chinese patients with PCNSL have distinct characteristics. Further studies are warranted to confirm the prognostic value of these factors and to optimize treatments for these patients.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/terapia , China , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
4.
Medicine (Baltimore) ; 98(46): e17949, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725652

RESUMO

Recently, we have proposed a theoretical modified tri-exponential model for multi-b-value diffusion-weighted imaging (DWI) to measure the cytoplasmic organelle water fraction (COWF). This study aims to investigate whether COWF maps are effective in evaluating the malignant degree of gliomas and distinguishing primary central nervous system lymphomas (PCNSL) from gliomas.We performed this retrospective study based on our prospectively collected data. All patients underwent preoperative multi-b-value DWI. Parametric maps were derived from multi-b-value DWI maps using the modified tri-exponential model. Receiver operating characteristic analyses were used to assess the diagnostic accuracy of the parameter maps. Pearson correlation coefficients were calculated to investigate the correlations between the parameters and the Ki-67 proliferation index.A total of 66 patients were enrolled, including 16 low-grade gliomas (LGG), 45 high-grade gliomas (HGG), and 5 PCNSL. The mean COWF values were significantly different among LGG (3.1 ±â€Š1.4%), HGG (6.9 ±â€Š2.8%), and PCNSL (14.0 ±â€Š2.2%) (P < .001). The areas under the curves of the mean COWF value in distinguishing HGG from LGG and distinguishing PCNSL from gliomas were 0.899 and 0.980, respectively. The mean COWF value had a moderate correlation with the Ki-67 proliferation index (r = 0.647).The COWF map is useful in malignant grading of gliomas, and may be helpful in distinguishing PCNSL from gliomas.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/patologia , Organelas/patologia , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/diagnóstico , Diagnóstico Diferencial , Feminino , Glioma/diagnóstico , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
5.
Zhonghua Bing Li Xue Za Zhi ; 48(11): 861-866, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31775435

RESUMO

Objective: To assess clinical features and treatment outcomes in immunocompetent patients with primary central nervous system lymphoma (PCNSL). Methods: Sixty-two patients with PCNSL who attended Guangdong General Hospital between January 1998 and January 2012 were included. Survival curves were estimated using Kaplan-Meier survival methodology and statistical significance of continuous was assessed via the Cox proportional hazard model. Results: The median age of the patient cohort was 56 years, and the male to female ratio was 1.14∶1.00. The common presentations were increased intracranial pressure symptoms and neuron damage. Performance status of 54 (54/62, 87.1%) patients were the international prognostic index (IPI) 0-2. Diffuse large B-cell lymphoma (57/62, 91.9%) was most common, and the rest were T-cell lymphoma (4/62,6.4%) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (1/62, 1.6%). In the series, 32 patients (32/62, 51.6%) had multiple lesions. Involvement of deep structures was found in 30 (30/62, 48.4%) patients. An elevated serum LDH level was detected in 19 (19/62, 30.6%) patients and the Ki-67 index was ≥90% in 38 (38/62, 61.3%) patients. Univariate analysis showed patients who were female, age<60 years, had WHO Eastern Cooperative Oncology Group performance status grade 0-2, single lesion, absence of deep structures involvement and normal LDH level showed better 2-year survival rate and longer median survival time. Significance was only seen in the normal LDH level group. Multivariate Cox regression analysis revealed that radical surgery only and Rituximab+ high-dose of methotrexate+ whole brain radiation therapy (WBRT) were independent prognostic indicators in PCNSL patients (P<0.05). Conclusions: PCNSL is a rare but aggressive tumor with poor prognosis. Patients treated with high-dose of methotrexate combining with rituximab, followed by WBRT have a better prognosis and longer survival time, and thus these could probably be a promising treatment.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/terapia , Protocolos de Quimioterapia Combinada Antineoplásica , Feminino , Humanos , Linfoma Difuso de Grandes Células B , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
6.
Fortschr Neurol Psychiatr ; 87(10): 571-575, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31627239

RESUMO

The CLIPPERS syndrome is a chronic, inflammatory disorder of the central nervous system of unknown etiology, which was first described in 2010 by Pittock and colleagues. It is characterized by typical magnetic resonance imaging (MRI) changes with lesions mainly in the brainstem, a perivascular, lymphohistiocytic inflammatory process and significant improvement under glucocorticoid therapy. Here we describe the case of a 40-year-old male who presented initially with typical clinical and radiological signs of CLIPPERS syndrome and who achieved complete remission under immunosuppressive therapy. Two years later, he presented with severe headaches. The MRI showed a reappearance of the lesion in the cerebellum, but now with a confluent character. The first brain biopsy showed lymphoproliferation. A second brain biopsy could finally confirm the suspected diagnosis of a primary CNS lymphoma.


Assuntos
Tronco Encefálico/diagnóstico por imagem , Tronco Encefálico/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico , Linfoma/diagnóstico , Adulto , Biópsia , Neoplasias do Sistema Nervoso Central/patologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Cefaleia , Humanos , Linfoma/patologia , Imagem por Ressonância Magnética , Masculino , Síndrome
7.
Ann Hematol ; 98(11): 2561-2567, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31515574

RESUMO

Overt central nervous system (CNS) involvement in aggressive non-Hodgkin's lymphoma (NHL) is rare at diagnosis. Much effort is put to identify risk factors for occult CNS involvement, and the risk assessment of CNS relapse. Prophylactic treatment carries risk of adverse events and its efficacy is not clear. Detection of cerebrospinal fluid molecular gene rearrangement (GRR) as a method to detect occult disease has been studied in acute leukemia and primary CNS lymphoma. To date, the capacity of a positive GRR in newly diagnosed NHL patients to predict CNS relapse has not been addressed. We retrospectively studied the prognostic value of GRR in cerebrospinal fluid samples of 148 newly diagnosed patients with high grade NHL. We demonstrate that positive GRR at diagnosis does not affect PFS or OS and did not predict CNS relapse. However, although numbers were small, repeated positive samples (≥ 2) correlated with a higher risk for CNS relapse (p = 0.048), possibly stressing the need for an aggressive preventive approach.


Assuntos
Neoplasias do Sistema Nervoso Central , Rearranjo Gênico , Linfoma não Hodgkin , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/genética , Linfoma não Hodgkin/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Crit Rev Oncol Hematol ; 141: 139-145, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31295667

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of diffuse large B-cell lymphoma. The frontline treatment with high-dose methotrexate based immunochemotherapy is not curative for the majority of patients. Gene expression profiling and next-generation sequencing have recently provided plethora of data shedding light on pathogenic mechanisms sustain PCNSL and identifying potential vulnerable mechanisms to be explored therapeutically. Here, we review established molecular drivers of PCNSL and targeted drugs that may change the current therapeutic paradigm.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Terapia de Alvo Molecular , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Terapias em Estudo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Metotrexato/administração & dosagem , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Terapias em Estudo/métodos , Terapias em Estudo/tendências
9.
Indian J Pathol Microbiol ; 62(3): 368-374, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31361222

RESUMO

Background: Metastatic tumors are the most common central nervous system (CNS) tumors wherein the primary site remains unknown in most of the cases. Aim: The study was carried out to evaluate metastatic CNS tumors with unknown primary by using simplified diagnostic (clinico-histopathologic) approach. Material and Methods: A 2 years study was conducted on 32 cases of CNS metastases having unknown primary tumors in a neurosciences institute. Statistical Analysis: All the results were prepared using software version of SPSS 22. Results: The most common metastatic site found in brain was cerebrum (59.3%) [frontal > frontoparietal > parieto-occipital > temporal] [left cerebrum > right cerebrum], followed by cerebellum (12.5%), spinal cord (9.3%), and leptomeninges (3.12%). Most of the metastatic tumors presented as ill-defined (34%) rather than well-defined (22%) lesions with ring enhancement seen only in 16% of the cases on magnetic resonance imaging (MRI).On histopathology findings with targeted immunohistochemistry, most common histological tumor type identified irrespective of site was adenocarcinoma (68.7%), followed by squamous cell carcinoma (15.6%) and poorly differentiated carcinoma (12.5%). Only one case of lymphoma was reported. Corroborating all the above findings along with clinical history and other relevant investigations, primary sites could be detected in 23 cases (71.8%).The most common primary site deduced was lungs (39.1%), followed by thyroid (17.3%), breast in females (13.0%), gastrointestinal tract (8.6%), and prostate in males (4.3%). Only in nine cases (28.1%) with mainly poorly differentiated histopathological type, primary site remained unknown. Conclusion: Detection of the primary site in metastatic CNS tumors is possible by adopting this simple and effective diagnostic approach at centers/hospitals having cost and other constraints.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/secundário , Neoplasias Primárias Desconhecidas/diagnóstico , Adenocarcinoma/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Cérebro/diagnóstico por imagem , Cérebro/patologia , Feminino , Humanos , Imuno-Histoquímica , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
World Neurosurg ; 130: e1091-e1097, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323401

RESUMO

BACKGROUND: Primary melanocytic neoplasms of the central nervous system (CNS) are rare and account for 1% of all melanomas. This study used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the epidemiology of primary CNS melanoma and further characterize their treatment. METHODS: Data from the National Cancer Institute SEER program, collected from 1973-2015, were retrospectively analyzed. A total of 86 records of malignant melanoma cases with CNS as the primary site were identified, and 54 patients were studied based on the inclusion criteria. Demographic, tumor, and treatment regimen effectiveness were studied. RESULTS: A total of 54 patients were included in this study. Tumors were distributed evenly in size and localized primarily to the cerebral meninges and spinal cord. A total of 13% of patients underwent biopsy, 40.7% gross total resection (GTR), 7.4% subtotal resection (STR), 46.3% radiation therapy (RT), and 27.3% chemotherapy (CT) in a variety of treatment combinations. GTR alone and STR + RT resulted in increased disease-specific survival compared to biopsy alone, but no survival benefit was found with biopsy with RT and/or CT as well as STR alone. CONCLUSIONS: To our knowledge, this is the largest single database study completed for primary malignant melanoma of the CNS. The study identified the need for tumor resection for the proper treatment of these lesions, particularly GTR. GTR could be paired with adjuvant RT or RT + CT providing survival benefit as well. In cases when GTR is unable to be completed, STR + RT provides significant improvement in survival compared to biopsy alone.


Assuntos
Neoplasias do Sistema Nervoso Central/epidemiologia , Melanoma/epidemiologia , Vigilância da População , Programa de SEER/tendências , Adulto , Idoso , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/terapia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/terapia , Pessoa de Meia-Idade , Vigilância da População/métodos , Estudos Retrospectivos
11.
Diagn Pathol ; 14(1): 56, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31189479

RESUMO

OBJECTIVES: Standard treatment with a thiotepa-based regimen in countries with a limited resource is less feasible. Aims of the study were to evaluate the treatment outcome, and identify the prognostic factors in patients with primary central nervous system lymphoma (PCNSL). METHODS: We conducted a retrospective study of 43 patients diagnosed with PCNSL, DLBCL subtype, who were treated with either HDMTX-based regimen, whole brain radiotherapy (WBRT), or both between 2010 and 2017. RESULTS: There were 43 patients with a median age of 65 years (range 34-89 years). Protein expression of CD10, Bcl6, MUM1, Bcl2 and MYC were found in 19, 86, 91, 91 and 23%, respectively. Both germinal center B cell (GCB) and double-expressor (MYC+/Bcl2+) lymphomas were found in 21%. Multiple brain lesions and maximum tumor diameter (MTD) ≥5 cm were seen in 27 and 10 patients, respectively. Chemotherapy combined with WBRT, chemotherapy and WBRT were given to 20, 14 and 9 patients, respectively. Overall complete remission (CR) rate was 55.8%. Those receiving a combined-modality therapy had a higher CR rate than those treated with either chemotherapy (75% versus 36%, p = 0.036) or WBRT (75% versus 44%, p = 0.109). Median follow-up time was 17 months, and a 7-year overall survival (OS) was 40%. Features associated with a prolonged OS were an ECOG score ≤ 2 (p = 0.001), multiple brain lesions (p = 0.010), multiple area of brain involvement (p = 0.023), MTD < 5 cm (p = 0.004), GCB subtype (p = 0.003) and positive CD10 staining (p = 0.007). Expression of Bcl2 protein was associated with a significantly worse OS in the non-GCB DLBCL patients. DISCUSSION: The factors affecting treatment outcomes in PCNSL were cell of origin of DLBCL, lesion characteristics, patients' status and treatment regimen.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma Difuso de Grandes Células B/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/mortalidade , Terapia Combinada/métodos , Feminino , Centro Germinativo/metabolismo , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Resultado do Tratamento
12.
J Neurooncol ; 144(1): 107-115, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190317

RESUMO

BACKGROUND: Immunodeficiency is a major risk factor for primary central nervous system lymphoma (PCNSL), but data on the disease in immunocompromised hosts are scarce. We aimed to define clinical and imaging features and determine prognostic factors for immunodeficiency-associated PCNSL. METHODS: All PCNSL cases seen at Yale-New Haven Hospital between 2002 and 2017 were retrospectively screened for immunodeficiency. For patients with immunosuppression, biopsies were evaluated and clinical data were collected. Predictors of survival were identified using Kaplan-Meier survival analysis and log-rank test. p values < 0.05 were considered significant. RESULTS: 23 patients with immunodeficiencies were identified: eleven on immunosuppressants after solid organ transplantation, seven with human immunodeficiency virus infection, and five on immunosuppressive treatment due to various autoimmune disorders. PCNSL cases were largely Epstein-Barr-Virus positive (78%), histologically classified as diffuse large B cell lymphomas (87%), and showed peripheral contrast enhancement (81%) and corresponding heterogeneous diffusion-weighted imaging patterns (DWI) on magnetic resonance imaging (MRI) (71%). Median overall survival was 31 months. Age > 60 years at diagnosis (p < 0.01), peripheral enhancement of the mass on MRI (p = 0.04), heterogeneous DWI patterns (p = 0.04), and clonal immunoglobulin heavy chain gene rearrangement (IgHR) (p = 0.03) were found to be negative prognostic markers. CONCLUSIONS: Immunodeficiency-associated PCNSL presents with similar clinical, pathological and imaging features. Age > 60 years, clonal IgHR, heterogeneous DWI pattern and peripheral enhancement on MRI may serve as predictors of less favorable outcome.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias do Sistema Nervoso Central/diagnóstico , Síndromes de Imunodeficiência/complicações , Linfoma não Hodgkin/diagnóstico , Adolescente , Adulto , Idoso , Neoplasias do Sistema Nervoso Central/etiologia , Neoplasias do Sistema Nervoso Central/metabolismo , Criança , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Linfoma não Hodgkin/etiologia , Linfoma não Hodgkin/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
13.
Hematol Oncol ; 37 Suppl 1: 15-18, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31187523

RESUMO

Primary central nervous system lymphoma is a rare subtype of non-Hodgkin lymphoma that is confined to the brain, leptomeninges, or the eye and is associated with a relatively poor prognosis compared to other extranodal diffuse large B-cell lymphomas. However, methotrexate-based induction chemotherapy followed by consolidative chemotherapy or high-dose therapy and autologous stem cell transplantation is associated with improved survival and reduced neurotoxicity. Aberrant activation of B-cell receptor signaling and activation of nuclear factor kappa beta is a frequent genetic alteration and offers opportunities for targeted therapies in this lymphoma subtype.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma/terapia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/etiologia , Terapia Combinada , Gerenciamento Clínico , Humanos , Incidência , Linfoma/diagnóstico , Linfoma/epidemiologia , Linfoma/etiologia , Imagem Multimodal/métodos , Guias de Prática Clínica como Assunto , Prognóstico , Resultado do Tratamento
14.
Turk Patoloji Derg ; 35(3): 173-184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31107540

RESUMO

Intraoperative consultations or frozen sections for central nervous system (CNS) tumors present a significant challenge for surgical pathologists because of their relative rarity and diversity. Yet, such lesions are encountered by every surgical pathologist, and a basic understanding of clinical, radiological and genetic information is critical to successfully evaluate CNS frozen sections. It is often beneficial to have a systematic approach or an algorithm, and to be aware of the common pitfalls and mimickers when dealing with these lesions. We propose such an algorithm in an effort to construct a sensible approach to CNS frozen sections that considers recent developments in the WHO CNS tumor classification. The algorithm was developed for surgical pathologists who are occasionally faced with making diagnosis of CNS tumors on frozen sections. To test the algorithm and its practicability, we selected a group of tumors among a total of 3288 consecutive intraoperative consultations performed at UCSF between 2013 and 2017. The selected cases represented lesions that may be encountered in everyday surgical pathology and constituted a fair reflection of the main group. The algorithm was used by three of the authors who did not have formal neuropathology training and had been in surgical pathology practice for at least 3 years. There was a very high level of concordance among the authors' diagnosis (interobserver concordance: 0.83-0.97-kappa value) using the algorithm with high intraobserver reliability (concordance 93%, p < 0.001). We suggest that an algorithmic approach is an effective means for the surgical pathologists, and may help reach diagnosis during frozen sections.


Assuntos
Algoritmos , Neoplasias do Sistema Nervoso Central/diagnóstico , Secções Congeladas , Patologia Cirúrgica/métodos , Humanos
15.
Blood ; 134(3): 252-262, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31118164

RESUMO

Patients with primary central nervous system lymphoma (PCNSL) are treated with high-dose methotrexate-based chemotherapy, which requires hospitalization and extensive expertise to manage related toxicity. The use of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could overcome these difficulties, but blood-brain barrier (BBB) penetration of related drugs is poor. Tumor necrosis factor-α coupled with NGR (NGR-hTNF), a peptide targeting CD13+ vessels, induces endothelial permeabilization and improves tumor access of cytostatics. We tested the hypothesis that NGR-hTNF can break the BBB, thereby improving penetration and activity of R-CHOP in patients with relapsed/refractory PCNSL (NCT03536039). Patients received six R-CHOP21 courses, alone at the first course and preceded by NGR-hTNF (0.8 µg/m2) afterward. This trial included 2 phases: an "explorative phase" addressing the effect of NGR-hTNF on drug pharmacokinetic parameters and on vessel permeability, assessed by dynamic contrast-enhanced magnetic resonance imaging and 99mTc-diethylene-triamine-pentacetic acid-single-photon emission computed tomography, and the expression of CD13 on tumor tissue; and an "expansion phase" with overall response rate as the primary end point, in which the 2-stage Simon Minimax design was used. At the first stage, if ≥4 responses were observed among 12 patients, the study accrual would have continued (sample size, 28). Herein, we report results of the explorative phase and the first-stage analysis (n = 12). CD13 was expressed in tumor vessels of all cases. NGR-hTNF selectively increased vascular permeability in tumoral/peritumoral areas, without interfering with drug plasma/cerebrospinal fluid concentrations. The NGR-hTNF/R-CHOP combination was well tolerated: there were only 2 serious adverse events, and grade 4 toxicity was almost exclusively hematological, which were resolved without dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with 9 confirmed responses (75%; 95% confidence interval, 51-99), 8 of which were complete. In conclusion, NGR-hTNF/R-CHOP was safe in these heavily pretreated patients. NGR-hTNF enhanced vascular permeability specifically in tumoral/peritumoral areas, which resulted in fast and sustained responses.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacocinética , Fator de Necrose Tumoral alfa/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Barreira Hematoencefálica/diagnóstico por imagem , Antígenos CD13/metabolismo , Permeabilidade da Membrana Celular , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/metabolismo , Neoplasias do Sistema Nervoso Central/mortalidade , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imuno-Histoquímica , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/mortalidade , Masculino , Neuroimagem/métodos , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Projetos de Pesquisa , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Fator de Necrose Tumoral alfa/administração & dosagem , Vincristina/efeitos adversos , Vincristina/uso terapêutico
16.
Brain Pathol ; 29(4): 469-472, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31038238

RESUMO

cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) was established to provide a forum to evaluate and recommend proposed changes to future CNS tumor classifications. From 2016 to 2019 (Round 1), cIMPACT published four updates. Update 1 clarified the use of the term NOS (Not Otherwise Specified) and proposed use of the additional term NEC (Not Elsewhere Classified). Update 2 issued clarifications regarding two diagnoses: Diffuse Midline Glioma, H3 K27M-mutant and Diffuse Astrocytoma/Anaplastic Astrocytoma, IDH-mutant. Update 3 proposed molecular criteria that could be used in the setting of an IDH-wildtype diffuse or anaplastic astrocytic glioma without histological features of glioblastoma to infer that the tumor would behave similarly to a grade IV glioblastoma. Update 4 suggested that, in children and young adults, subtypes of IDH-wildtype/H3-wildtype diffuse gliomas may have distinct clinical features in the setting of a BRAFV600E mutation, FGFR1 alteration, other MAPK pathway alteration, or a MYB or MYBL1 rearrangement. The practical diagnostic relevance of these cIMPACT proposals is highlighted in this summary.


Assuntos
Neoplasias Encefálicas/classificação , Neoplasias do Sistema Nervoso Central/classificação , Neuropatologia/classificação , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Humanos
17.
Rinsho Shinkeigaku ; 59(6): 365-370, 2019 Jun 22.
Artigo em Japonês | MEDLINE | ID: mdl-31142712

RESUMO

A 67-year-old male was transferred to our hospital with diplopia, decreased deep tendon reflex and ataxia. He had been suspected Fisher syndrome because of previous upper respiratory tract infection. A cerebrospinal fluid examination showed marked hypoglycorrhachia, pleocytosis and elevated protein, and cytological examination suggested malignant lymphoma. Abdominal computed tomography revealed a left adrenal mass. A biopsy of the left adrenal mass revealed diffuse large B-cell lymphoma. He was treated with a combination of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin and prednisolone) and intrathecal administration of methotrexate, cytarabine and prednisolone. Neurological symptoms were gradually improved. Malignancy should be considered in addition to bacterial, fungal or tuberculous meningitis in a case with marked hypoglycorrhachia.


Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Glucose/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/líquido cefalorraquidiano , Linfoma Difuso de Grandes Células B/diagnóstico , Doenças do Nervo Oculomotor/etiologia , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Nervoso Central/complicações , Neoplasias do Sistema Nervoso Central/patologia , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Diagnóstico por Imagem , Doxorrubicina/administração & dosagem , Humanos , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Masculino , Metotrexato/administração & dosagem , Prednisolona/administração & dosagem , Prednisona/administração & dosagem , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagem
18.
Am Soc Clin Oncol Educ Book ; 39: 454-466, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31099614

RESUMO

Primary central nervous system (CNS) lymphoma (PCNSL) is an aggressive form of non-Hodgkin lymphoma that remains confined to the CNS neuroaxis during its natural history of disease and is therefore considered stage IE disease. PCNSL is diffuse large B-cell lymphoma (DLBCL) morphology in more than 95% of patients and is designated primary diffuse large B-cell lymphoma of the CNS on the basis of the 2017 World Health Organization classification of hematopoietic and lymphoid tumors. Rapidly evolving therapeutic paradigms have been linked to evidence of progress in PCNSL, a disease long considered to be incurable. Increasing evidence supports the need for efficient diagnosis, staging, and initiation of therapy, ideally at centers with experience with this type of brain cancer. High-dose methotrexate (MTX) remains a cornerstone of induction regimens, and most data support the use of rituximab. However, clinical research challenges must address key questions, including the development of ever more effective and less toxic induction regimens and the selection of the most appropriate and effective consolidation approaches, as well as the fact that, increasingly, PCNSL affects older patients who do not tolerate strong genotoxic irradiation or high-dose chemotherapy (HDC)-based strategies. Maintenance therapy, immunotherapy, and the implementation of targeted agents on the basis of the molecular and biologic properties of the disease create opportunities for precision medicine and the potential for long-term disease-free survival and cure, with minimal treatment-related neurotoxicity, for a greater fraction of patients.


Assuntos
Neoplasias do Sistema Nervoso Central/terapia , Linfoma não Hodgkin/terapia , Fatores Etários , Neoplasias do Sistema Nervoso Central/diagnóstico , Tomada de Decisão Clínica , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Gerenciamento Clínico , Resistencia a Medicamentos Antineoplásicos , Detecção Precoce de Câncer , Humanos , Linfoma não Hodgkin/diagnóstico , Estadiamento de Neoplasias , Medicina de Precisão , Recidiva , Retratamento
19.
Am Soc Clin Oncol Educ Book ; 39: e59-e69, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31099629

RESUMO

Metastases to the central nervous system (CNS) are associated with considerable morbidity and mortality in patients with cancer. Historically, very few systemic therapies have shown efficacy in this patient population. Emerging data are now demonstrating that whole-brain radiation therapy, previously considered the mainstay of treatment of brain metastases, is associated with high rates of neurotoxicity. In this new era of targeted therapy and immunotherapy, clinical outcomes are improving, and patients are living longer. Despite these improvements, there is an urgent need to design central nervous system-penetrant compounds that target the genetic mutations enriched in brain metastases and to bring these to clinical trials.


Assuntos
Neoplasias do Sistema Nervoso Central/secundário , Neoplasias do Sistema Nervoso Central/terapia , Imunoterapia , Terapia de Alvo Molecular , Biomarcadores Tumorais , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Neoplasias do Sistema Nervoso Central/diagnóstico , Gerenciamento Clínico , Humanos , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias Pulmonares/patologia , Melanoma/patologia , Terapia de Alvo Molecular/efeitos adversos , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Padrão de Cuidado , Resultado do Tratamento
20.
Diagn Pathol ; 14(1): 45, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31109360

RESUMO

BACKGROUND: Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) is a rare intracranial tumor, defined as DLBCL arising from the brain, spinal cord, leptomeninges and eye, with an overall annual incidence of 5 cases per million. The primary CNS anaplastic variant of DLBCL (A-DLBCL) is even less common; to our knowledge, there are only two other case reports in the literature. The aim of this report is to present rare cases of primary CNS A-DLBCL and study their clinicopathologic and genetic features. CASE PRESENTATION: We report 3 patients, two men and one woman, aged 54, 55 and 67 years old, with primary CNS A-DLBCL. All 3 patients had a high International Extranodal Lymphoma Study Group (IELSG) score; although the patients were treated with methotrexate-based regimens and/or with radiation therapy, the overall survival was only 2, 5, and 8 months. All 3 patients presented with characteristic features of perivascular space infiltration with bizarre-shaped tumor cells, leading to the diagnosis of primary CNS A-DLBCL. Concurrent of MYC and BCL2 and/or BCL6 abnormalities and MYC/BCL2 double-expressor DLBCL occurred in all 3 patients; two patients had MYC/BCL2/BCL6 triple extra copies, and one patient had MYC extra copy and BCL6 translocation. All 3 patients displayed mutations in MYD88 L265P and nuclear positivity for RELA, RELB and/or c-Rel, indicating constitutive activation of the NF-κB pathway. CONCLUSIONS: These cases shed light on the unique genetic alterations and biological features of primary CNS A-DLBCL. Patients with primary CNS A-DLBCL may often have a MYC/BCL2 double-expressor and concurrent MYC and BCL2 and/or BCL6 genetic abnormalities, as well as constitutive activation of the NF-κB pathway. Primary CNS A-DLBCL follows a very aggressive disease course and poor prognosis. In the future, a large number of cases should be analyzed, and the evaluation of molecular genetic characteristics could help with practical and therapeutic implications for primary CNS A-DLBCL.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genética , Idoso , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Mutação , NF-kappa B/metabolismo , Prognóstico
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