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BACKGROUND: To assess the genetic characteristics of central nervous system (CNS) metastases from non-small-cell lung cancer (NSCLC), we gathered the genetic profiles of brain metastases (BM) and leptomeningeal metastases (LM). Our objective was to identify genetic factors contributing to poorer overall survival (OS) in NSCLC patients with LM. METHODS: This study included 25 consecutive patients with BM and 52 patients with LM from Guangdong Sanjiu Brain Hospital. All participants underwent 168-target panel sequencing. RESULTS: Among the 25 patients with BM, TP53 was the most frequently mutated gene (44%), followed by driver genes such as EGFR and BRAF (40% and 20%, respectively). In patients with BM, EGFR_amp and CDK4 were also frequently mutated, with rates of 20% and 16%, respectively. The genetic landscape of patients with LM differed, with the top mutated genes being EGFR, TP53, EGFR_amp, CDKN2A, CCNE1, CDK4, PMS2, and PIK3CA, with mutation rates of 77%, 69%, 31%, 29%, 13%, 13%, 13%, and 12%, respectively. In our study, patients with LM exhibited significantly worse OS compared to those with BM (p = 0.029). The mutation rates of TP53, EGFR_amp, and CDKN2A varied between patients with LM and those with BM, at 69.23% vs. 44%, 30.77% vs. 20%, and 28.85% vs. 12%, respectively. Further exploration revealed that patients with BM with TP53 mutations had a shorter OS than patients without TP53 mutations (p = 0.014). Similarly, patients with LM and TP53 mutations presented with worse OS than those without TP53 mutations (p = 0.0067). LM patients with CDKN2A deletions had worse OS than those without CDKN2A deletions (p = 0.037). Additionally, patients with EGFR_amp had a shorter OS than those without EGFR_amp (p = 0.044). CONCLUSIONS: Patients with LM exhibited significantly worse OS than those with BM. Gene signatures, such as TP53, EGFR_amp, and CDKN2A, may account for shorter outcomes in patients with LM.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Inibidores de Proteínas Quinases/uso terapêutico , Receptores ErbB/genética , Mutação/genéticaRESUMO
Diffuse leptomeningeal glioneuronal tumors (DLGNTs) are rare central nervous system tumors of childhood that were recently described as a new entity. DLGNTs usually manifest with symptoms related to increased intracranial pressure or spinal cord compression. The classic radiological feature is a widespread leptomeningeal enhancement that may involve the entire neuroaxis. Microscopic examination demonstrates oligodendroglial-like cells that are positive for OLIG2, MAP2, and S100 and negative for IDH-1. Anaplastic features occur in some cases. Molecularly, DLGNTs are characterized by chromosome arm 1p deletion and alteration of a mitogen-activated protein kinase (MAPK) pathway gene, most commonly BRAF-KIAA1549 fusion. There is no established grading system for these tumors, which may have an indolent or aggressive behavior. Treatment usually involves chemotherapy and radiation therapy.
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Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Neoplasias Meníngeas , Feminino , Humanos , Criança , Neoplasias Meníngeas/patologia , Neoplasias do Sistema Nervoso Central/patologiaRESUMO
Introduction Leptomeningeal carcinomatosis results from metastatic neoplastic cells that reach the leptomeninges through the cerebrospinal fluid. The presentation of the disease is variable, making prognosis challenging. However, the presence of intracranial hypertension is common, which has prompted new treatments to mitigate this effect. Objective To report the role of neurosurgery in the treatment of leptomeningeal carcinomatosis, as well as its advances. Methodology Literature review with a search of the PubMed database, between 2011 and 2021, using the following descriptors: Neurosurgery, Leptomeningeal Carcinomatosis, Cerebrospinal and Treatment. A total of 42 articles were found, 16 of which were selected. Results The shunt insertion considerably improved the effects of cranial hypertension, increasing the average survival time of patients by 3.5 months after surgery. The Ommaya reservoir is also a viable option due to its convenience and safety. The V-Port, on the other hand, has overcome the challenges of conventional devices, with shorter operating times (42 minutes), smaller skin incisions, and no reports of postoperative infection. Conclusion Devices for the treatment of leptomeningeal carcinomatosis have been steadily improving, simplifying surgical procedures and benefiting patients.
Introdução A carcinomatose leptomeníngea resulta de células neoplásicas metastáticas que atingem as leptomeninges através do líquido cefalorraquidiano. A apresentação da doença é variável, tornando o prognóstico desafiador. No entanto, a presença de hipertensão intracraniana é comum, o que levou a novos tratamentos para mitigar esse efeito. Objetivo Relatar o papel da neurocirurgia no tratamento da carcinomatose leptomeníngea, bem como seus avanços. Metodologia Crítica literária com busca na base de dados PubMed, entre 2011 e 2021, utilizando os seguintes descritores: Neurocirurgia, Carcinomatose Leptomeníngea, Cefalorraquidiana e Tratamento. Foram encontrados 42 artigos, dos quais 16 foram selecionados. Resultados A inserção do shunt melhorou consideravelmente os efeitos da hipertensão craniana, aumentando o tempo médio de sobrevida dos pacientes em 3,5 meses após a cirurgia. O reservatório de Ommaya também é uma opção viável devido à sua conveniência e segurança. O V-Port, por outro lado, superou os desafios dos dispositivos convencionais, com tempos de operação mais curtos (42 minutos), incisões cutâneas menores e sem relatos de infecção pós-operatória. Conclusão Os dispositivos para o tratamento da carcinomatose leptomeníngea vêm melhorando constantemente, simplificando os procedimentos cirúrgicos e beneficiando os pacientes.
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Purpose: Central nervous system (CNS) metastases are a significant burden in breast cancer (BC). Capecitabine is a frequent choice in this scenario, but data supporting its single-agent activity are scarce. We aimed to evaluate the intracranial efficacy of capecitabine in CNS metastases from BC. Methods: This retrospective cohort included patients with CNS metastases from BC treated with capecitabine at a single centre. Study endpoints were intracranial CNS objective response rate (CNS-ORR), intracranial CNS disease control rate (CNS-DCR), intracranial CNS progression-free survival (CNS-PFS) and overall survival (OS). Results: 209 patients were included; 41.6% hormone receptor-positive HER2-negative (HR + HER2-), 33.9% human epidermal growth factor receptor 2 positive (HER2+), and 26.4% triple-negative breast cancer (TNBC). Radiotherapy was performed in 90.4% and CNS surgery in 27.5%. Among patients accessible for intracranial response, 3-month CNS-ORR and CNS-DCR were 41.6% and 81.2%. CNS-ORR was numerically higher among TNBC (61% versus 38% in HR + HER2-BC and 35% in HER2 + BC) (p = 0.194). When considering patients who were not evaluable at 3-month as non-responders, the 3-month CNS-ORR was 19.1% (18.4% in HR + HER2-, 18.3% in HER2+, and 21.6% in TNBC). Nevertheless, TNBC was associated with lower CNS-PFS (p < 0.001) and OS (p < 0.001). Median PFS was 8.3 months in HR + HER2-, 5.0 months in HER2+, and 3.0 months in TNBC. Median OS was 8.7, 9.1 and 4.5 months, respectively. Conclusion: Among patients with BC and CNS metastases accessible for intracranial response at 3 months, intracranial activity was observed with capecitabine. These patients have a poor prognosis regardless of the BC subtype, especially in scenarios where newer therapeutic options are unavailable.
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Background: Leptomeningeal metastasis is an infrequent form of cancer expression, and it has a poor prognosis due to its torpid evolution and its challenging diagnosis. Case report: We report the case of a 68-year-old woman with rapidly progressing cognitive decline and focal epilepsy. Brain magnetic resonance imaging showed extensive gyriform hypersignal in the right precentral sulcus region, without mass effect, tenuous contrast uptake, and hydrocephalus with transependymal edema. The body tomographic study was negative for solid cancer and the 18F-FDG PET-CT revealed a severe hypermetabolism in the right lung upper lobe. These findings were suggestive of lung cancer with leptomeningeal metastasis. We performed a brain biopsy, finding atypical cells in the leptomeningeal region with positive immunohistochemical staining for CK7 and negative for CK20 corresponding to lung adenocarcinoma. The patient was evaluated in the oncology service and scheduled for radiotherapy and chemotherapy. Conclusions: Focal leptomeningeal disease is an entity that should be considered as a differential diagnosis in all cases of focal leptomeningitis. Timely diagnosis and adequate cancer management can increase patient survival.
Assuntos
Neoplasias Pulmonares , Neoplasias Meníngeas , Neoplasias Primárias Desconhecidas , Idoso , Feminino , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Primárias Desconhecidas/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaAssuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Sistema Nervoso Central/efeitos dos fármacos , Sistema Nervoso Central/fisiopatologia , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-ret , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Piridinas/farmacologia , Piridinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Feminino , Humanos , Neoplasias Meníngeas , Pessoa de Meia-IdadeRESUMO
PURPOSE: Leptomeningeal disease (LMD) is a rare but deadly complication of cancer in which the disease spreads to the cerebrospinal fluid and seeds the meninges of the central nervous system (CNS). Craniospinal irradiation (CSI) involves treatment of the entire CNS subarachnoid space and is occasionally used as a last-resort palliative therapy for LMD. METHODS: This review examined literature describing the role of CSI for LMD from solid and hematologic malignancies in adults. A search for studies published until September 1, 2020 was conducted using PubMed database. RESULTS: A total of 262 unique articles were identified. Thirteen studies were included for analysis in which a total of 275 patients were treated with CSI for LMD. Median age at time of irradiation was 43 years, and most patients had KPS score of 70 and higher. The most common cancers resulting in LMD were acute lymphocytic leukemia, breast cancer, and acute myelogenous leukemia. Median CSI dose was 30 Gy and 18% of patients were treated with proton radiation. 52% of patients had stable-to-improved neurologic symptoms. Median overall survival for the entire cohort was 5.3 months. Patients treated with marrow-sparing proton radiation had median OS of 8 months. The most common treatment toxicities were hematologic and gastrointestinal events. CONCLUSIONS: Despite advances in systemic and radiation therapies, LMD remains a devastating end-stage complication of some malignancies. Treatment-related toxicities can be a significant barrier to CSI delivery. In select patients with LMD, marrow-sparing proton CSI may provide safer palliation of symptoms and prolong survival.
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Radiação Cranioespinal , Neoplasias Meníngeas/radioterapia , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Avaliação de Estado de Karnofsky/estatística & dados numéricos , Leucemia Mieloide Aguda/patologia , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/secundário , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Dosagem RadioterapêuticaRESUMO
El síndrome de Sturge-Weber es un trastorno neurocutáneo, congénito, esporádico e infrecuente que afecta aproximadamente a 1 de cada 20 000 a 50 0000 nacidos vivos y que se relaciona con una mutación genética activadora somática en GNAQ. Clínicamente se caracteriza por la presencia de una mácula en vino de Oporto en la piel de territorio trigeminal, angiomatosis leptomeníngea y glaucoma. Puede asociarse a diferentes manifestaciones clínicas, de las cuales las crisis epilépticas representan la manifestación neurológica más frecuente que se asocia a un deterioro cognitivo importante en estos pacientes. En el presente artículo se realiza una revisión descriptiva de la literatura sobre los aspectos etiológicos, fisiopatológicos, de clasificación, clínicos, diagnósticos y del tratamiento del síndrome de Sturge-Weber.
Sturge-Weber syndrome is a rare, sporadic, congenital neurocutaneous disorder affecting approximately 1 in 20,000 to 50,000 live births that is associated with a somatic activating gene mutation in GNAQ. Clinically it is characterized by the presence of a port wine stain on the skin of trigeminal territory, leptomeningeal angiomatosis and glaucoma. It can be associated with different clinical manifestations, of which the epileptic seizures represents the most frequent neurological manifestation associated with significant cognitive impairment in these patients. This article makes a descriptive review of the literature on the etiological, pathophysiological, classification, clinical, diagnostic and treatment aspects of Sturge-Weber syndrome.
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Convulsões , Síndrome de Sturge-Weber , Mancha Vinho do Porto , Classificação , Nascido VivoRESUMO
The present report describes the case of a male 17-year-old patient who progressively developed a hydrocephalus and polyradiculopathy due to involvement of central nervous system (CNS) by a diffuse leptomeningeal glioneuronal tumor (DLGNT). The tumor had partial remission in response to the treatment with radiotherapy plus procarbazine, lomustine, and vincristine (PCV) chemotherapy, and the patient had improvement in function and pain levels. The current knowledge about DLGNT, including its clinical manifestations, imaging findings, histological characteristics, and treatment are revised and discussed in the present paper.
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Humanos , Masculino , Adulto Jovem , Oligodendroglioma/patologia , Oligodendroglioma/tratamento farmacológico , Oligodendroglioma/radioterapia , Neoplasias Meníngeas , Oligodendroglioma/diagnóstico por imagem , Polirradiculopatia/complicações , Derivação Ventriculoperitoneal/métodos , Hidrocefalia/complicaçõesRESUMO
Resumen El Síndrome de Sturge-Weber es un trastorno poco común del desarrollo neuroectodérmico, caracterizado por un angioma facial tipo nevus flammeus y una angiomatosis leptomeníngea, con frecuencia ipsilateral al nevus. Este síndrome predispone a calcificaciones, atrofia cerebral y convulsiones refractarias. Propósito: En este artículo se realiza una revisión de la literatura sobre el Síndrome de Sturge-Weber y se reporta el caso de un paciente de 18 meses de edad diagnosticado con esta patología que ingresa a urgencias por presentar cuadro febril de tres días y comienzo de convulsiones tónico clónicas localizadas en hemicuerpo derecho refractarias al tratamiento convencional; en esta revisión se resalta la importancia del diagnóstico y manejo oportuno al igual que un adecuado seguimiento. Desarrollo: se realizaron búsquedas en las bases de datos PubMed, Science Direct y Scielo, confirmando que aún se desconocen algunos aspectos de esta patología, sin embargo, con el descubrimiento de la mutación somática de GNAQ hay un amplio campo para próximas investigaciones. Hallazgos y conclusiones: Es importante en el ejercicio médico no pasar de alto las lesiones angiomatosas que posean una ubicación trigeminal en los recién nacidos, con el fin de establecer un diagnóstico oportuno e intentar conseguir un mejor desarrollo a futuro.
Abstract Sturge-Weber Syndrome is a rare developmental neuroectodermical disorder. It is characterized by a facial port-wine stain and a leptomeningeal angiomata, frequently localized ipsilateral to the facial port-wine stain. This syndrome predisposes either to brain atrophy, calcifications and refractory seizures. In this paper a Sturge-Weber Syndrome literature review was made and a 18 month aged child case with this diagnosis is reported. He was admitted to the emergency department of a local hospital with a history of three days of fever and tonic-clonic seizures localized on the right side and refractory to conventional treatment. This review highlights the importance of an early diagnosis and an appropriate follow up. To carry out this review a search in PubMed, Science Direct and Scielo databases was done, confirming that there are some issues about this disorder that are still unknown. However, with the GNAQ somatic mutation discovery, there is an open field for new researches. It is very important in medical practice not to understimate a facial port-wine stain over trigeminal territory in newborns in order to make an early diagnosis and try to achieve a better future neurodevelopment.
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The pathological, immunohistochemical (IHC), and etiological features of lymphoma involving the nervous system (NS) in cats were analyzed through a retrospective study (2004-2017) in Rio Grande do Sul State, Brazil. The NS involvement was observed in 16 (12.2%) of 125 felines with lymphoma. Young cats were mainly affected, with a median of 24 months old. Most cases were secondary central NS lymphoma, whereas in three cats, the NS involvement was primary. IHC revealed 14 (87.5%) FeLV-positive, six FIV-positive, and one FeLV/FIV-negative cats. Distribution of feline lymphoma in the NS was 8/16 in the spinal cord, 7/16 in the brain, and 1/16 in the paravertebral nerves and ganglia (neurolymphomatosis). The lymphoma pattern in the spinal cord was exclusively extradural, often focal (6/8), and located in the lumbar (3/6), sacral (1/6), thoracic (1/6), and cervical segments (1/6). Brain neuroanatomical patterns were: leptomeningeal lymphomatosis (4/7), lymphomatous choroiditis (2/7), and intradural lymphoma (1/7). The feline with primary neurolymphomatosis presented a marked thickening of paravertebral nerves and ganglia from the sacral region. B-cell lymphoma (75%) was often diagnosed, and diffuse large B-cell lymphoma (DLBCL) (11/16) was the main subtype. T-cell lymphoma (25%) was less commonly observed and was classified as peripheral T-cell lymphoma (PTCL) (3/16) and T-cell lymphoblastic lymphoma (T-LBL) (1/16).(AU)
Os aspectos patológicos, imuno-histoquímicos (IHQ) e etiológicos do linfoma envolvendo o sistema nervoso de felinos foram analisados através de um estudo retrospectivo (período de 2004-2017) no Estado do Rio Grande do Sul, Brasil. O envolvimento do sistema nervoso foi observado em 16 (12,2%) dos 125 felinos com linfoma desse estudo e afetou principalmente, jovens com idade mediana de 24 meses. A grande maioria dos casos o linfoma era secundário no sistema nervoso central e somente em três gatos o linfoma foi primário do sistema nervoso. Na IHQ, 14 (87,5%) casos foram positivos para FeLV, seis (37,5%) para FIV, e um foi negativo para ambos. A distribuição do linfoma no sistema nervoso foi em 8/16 felinos na medula espinhal, 7/16 no encéfalo e em 1/16 em nervos e gânglios paravertebrais (neurolinfomatose). Na medula espinhal, o padrão do linfoma foi exclusivamente extradural e frequentemente focal (6/8), localizadas nos segmentos lombares (3/6), sacrais (1/6), torácicos (1/6) e cervicais (1/6). No encéfalo, os padrões neuroanatômicos observados foram: linfomatose leptomeningeal (4/7), coroidite linfomatosa (2/7), linfoma intradural (1/7). No felino diagnosticado com neurolinfomatose primária, foi observado acentuado espessamento dos nervos e gânglios paravertebrais da região sacral. Os linfomas de células de células B (75%) foram os mais frequentes e o principal tipo foi o linfoma difuso de grandes células B (11/16). Os linfomas de células T (25%), menos observados, foram classificados como linfomas de células T periférico inespecífico (3/16) e linfoma linfoblástico T (1/16).(AU)
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Animais , Gatos , Gatos/anormalidades , Neurolinfomatose/patologia , Linfoma/etiologia , Linfoma/patologiaRESUMO
The pathological, immunohistochemical (IHC), and etiological features of lymphoma involving the nervous system (NS) in cats were analyzed through a retrospective study (2004-2017) in Rio Grande do Sul State, Brazil. The NS involvement was observed in 16 (12.2%) of 125 felines with lymphoma. Young cats were mainly affected, with a median of 24 months old. Most cases were secondary central NS lymphoma, whereas in three cats, the NS involvement was primary. IHC revealed 14 (87.5%) FeLV-positive, six FIV-positive, and one FeLV/FIV-negative cats. Distribution of feline lymphoma in the NS was 8/16 in the spinal cord, 7/16 in the brain, and 1/16 in the paravertebral nerves and ganglia (neurolymphomatosis). The lymphoma pattern in the spinal cord was exclusively extradural, often focal (6/8), and located in the lumbar (3/6), sacral (1/6), thoracic (1/6), and cervical segments (1/6). Brain neuroanatomical patterns were: leptomeningeal lymphomatosis (4/7), lymphomatous choroiditis (2/7), and intradural lymphoma (1/7). The feline with primary neurolymphomatosis presented a marked thickening of paravertebral nerves and ganglia from the sacral region. B-cell lymphoma (75%) was often diagnosed, and diffuse large B-cell lymphoma (DLBCL) (11/16) was the main subtype. T-cell lymphoma (25%) was less commonly observed and was classified as peripheral T-cell lymphoma (PTCL) (3/16) and T-cell lymphoblastic lymphoma (T-LBL) (1/16).(AU)
Os aspectos patológicos, imuno-histoquímicos (IHQ) e etiológicos do linfoma envolvendo o sistema nervoso de felinos foram analisados através de um estudo retrospectivo (período de 2004-2017) no Estado do Rio Grande do Sul, Brasil. O envolvimento do sistema nervoso foi observado em 16 (12,2%) dos 125 felinos com linfoma desse estudo e afetou principalmente, jovens com idade mediana de 24 meses. A grande maioria dos casos o linfoma era secundário no sistema nervoso central e somente em três gatos o linfoma foi primário do sistema nervoso. Na IHQ, 14 (87,5%) casos foram positivos para FeLV, seis (37,5%) para FIV, e um foi negativo para ambos. A distribuição do linfoma no sistema nervoso foi em 8/16 felinos na medula espinhal, 7/16 no encéfalo e em 1/16 em nervos e gânglios paravertebrais (neurolinfomatose). Na medula espinhal, o padrão do linfoma foi exclusivamente extradural e frequentemente focal (6/8), localizadas nos segmentos lombares (3/6), sacrais (1/6), torácicos (1/6) e cervicais (1/6). No encéfalo, os padrões neuroanatômicos observados foram: linfomatose leptomeningeal (4/7), coroidite linfomatosa (2/7), linfoma intradural (1/7). No felino diagnosticado com neurolinfomatose primária, foi observado acentuado espessamento dos nervos e gânglios paravertebrais da região sacral. Os linfomas de células de células B (75%) foram os mais frequentes e o principal tipo foi o linfoma difuso de grandes células B (11/16). Os linfomas de células T (25%), menos observados, foram classificados como linfomas de células T periférico inespecífico (3/16) e linfoma linfoblástico T (1/16).(AU)
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Animais , Gatos , Gatos/anormalidades , Linfoma/etiologia , Linfoma/patologiaRESUMO
Leptomeningeal carcinomatosis (LMC) refers to the infiltration of malignant cells in the pia-arachnoids. LMC is undiagnosed until autopsy in about 20% of cases. A nonspecific neurologic symptomatology makes diagnosis challenging; especially in the scenario of unknown malignancy. Diagnosis is made by the identification of malignant cells in CSF; though studies have shown that serial examination may be required for acceptable accuracy. We report 3 cases with distinct neurological presentations, negative cerebrospinal fluid (CSF) examinations and neurological imaging. A 52 year old woman with history of breast cancer on remission, a 2 year old male with left ear rhabdomyosarcoma status post resection, and a 59 year old woman with communicating hydrocephalus of unknown etiology. LMC was diagnosed at autopsy and confirmed by immunohistochemistry. LMC is a complication requiring a high level of clinical suspicion. Postmortem examination is an invaluable tool to confirm LMC as part of the multidisciplinary approach aiming towards the improvement of clinical diagnosis.
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Neoplasias da Mama/patologia , Hidrocefalia/patologia , Carcinomatose Meníngea/diagnóstico , Rabdomiossarcoma/patologia , Autopsia , Pré-Escolar , Feminino , Humanos , Masculino , Carcinomatose Meníngea/patologia , Pessoa de Meia-IdadeRESUMO
Object: Leptomeningeal Carcinomatosis (LCM) represents a state of systemic malignant disease with poor prognosis. The purpose of this study is to compare overall survival (OS) between intraventricular chemotherapy through Ommaya reservoir (OR) and chemotherapy through lumbar puncture (LP) in LCM. Patients and Methods: Forty adult patients with LCM were included. All patients underwent lumbar puncture and Magnetic resonance imaging (MRI). Thirty patients received chemotherapy through LP and 10 undergone colocation of Ommaya reservoir for intraventricular chemotherapy. Results: The most common symptom was headache (Present in 50%). The cranial nerves most affected were VI and VII. Leptomeningeal enhancement was the most frequent finding in MRI. The OS in the LP group was 4 months and Ommaya group was 9.2 months (p = 0.0006; CI:1.8-3), with statistical differences in favor to Intraventricular treatment. Proportional hazard regression showed that receiving chemotherapy through Ommaya reservoir was a protective factor (Hazard ratio = 0.258, Standard Error = 0.112, p = 0.002 and 95% CI 0.110-0.606). Using KPS as a factor did not affect the hazard ratio of Ommaya reservoir itself. Conclusions: OS was significantly higher in patients with Ommaya reservoir in spite of Karnofsky Performance Status (KPS) previous to chemotherapy. Therefore, intraventricular chemotherapy should be preferred over lumbar puncture chemotherapy administration if there are resources available.
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Trilateral retinoblastoma (TRb) presents a management challenge, since intracranial tumours are seldom times resectable and quickly disseminate. However, there are no risk factors to predict the final outcome in each patient. OBJECTIVE: To evaluate minimal disseminated disease (MDD) in the bone marrow (BM) and the cerebrospinal fluid (CSF) at diagnosis and during follow-up and reviewing its potential impact in the outcome of patients with TRb. METHODS AND ANALYSIS: We evaluated MDD in five patients with TRb, detecting the mRNA of CRX and/or GD2, in samples from BM and CSF, obtained at diagnosis, follow-up and relapse. RESULTS: Treatment involved intensive systemic chemotherapy in four patients, one did not receive this treatment and died of progression of the disease. Two patients underwent stem cell rescue. Three patients had leptomeningeal relapse and died. One patient remains disease-free for 84 months. RB1 mutations were identified in the five patients, all of them were null mutations. At diagnosis, one patient had tumour cells in the CSF, and none had the BM involved. Only one case of four presented MDD during follow-up in the CSF, without concomitant detection in the BM. On leptomeningeal relapse, no case had MDD in the BM. In all these cases, cells in the CSF were positive for GD2 and/or CRX. CONCLUSION: CSF dissemination always concluded in the death of the patient, without concomitant systemic dissemination denoting the importance of increasing treatment directed to the CSF compartment. The MDD presence could indicate a forthcoming relapse.
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Neoplasias Encefálicas/diagnóstico , Glândula Pineal/patologia , Pinealoma/diagnóstico , Neoplasias da Retina/diagnóstico , Retinoblastoma/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Células da Medula Óssea/patologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Proteínas do Líquido Cefalorraquidiano/genética , Pré-Escolar , Feminino , Transplante de Células-Tronco Hematopoéticas , Proteínas de Homeodomínio/genética , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , N-Acetilgalactosaminiltransferases/genética , Recidiva Local de Neoplasia , Glândula Pineal/efeitos dos fármacos , Pinealoma/tratamento farmacológico , Pinealoma/genética , RNA Mensageiro/genética , Neoplasias da Retina/tratamento farmacológico , Neoplasias da Retina/genética , Retinoblastoma/tratamento farmacológico , Retinoblastoma/genética , Proteínas de Ligação a Retinoblastoma/genética , Estudos Retrospectivos , Fatores de Risco , Transativadores/genética , Transplante Autólogo , Ubiquitina-Proteína Ligases/genéticaRESUMO
Os tumores neuroectodérmicos primitivos (PNET) são tumores malignos, não diferenciados, raramente apresentados na idade adulta, principalmente os de localização supratentorial. Apresentamos neste artigo o caso de um paciente de 19 anos, que nos chegou transferido de outro hospital com o diagnóstico de hidrocefalia. A existência do PNET associado a carcinomatose leptomeníngea foi comprovada como causa da hidrocefalia.
Primitive neuroectodermal tumors (PNET) are malignant tumors exceptionally present in adulthood, especially those with supratentorial location. In this article, we present the case of a young man who was transfer fromanother institutionwith the diagnosis of hydrocephalus; during his stay, we corroborated the presence of supratentorial PNET associated to leptomeningeal carcinomatosis that was a cause of hydrocephalus.
Assuntos
Humanos , Masculino , Adulto , Tumores Neuroectodérmicos Primitivos/complicações , Carcinomatose Meníngea/complicações , Hidrocefalia/etiologiaAssuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Carcinomatose Meníngea/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Relação Dose-Resposta a Droga , Cloridrato de Erlotinib , Éxons , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Carcinomatose Meníngea/genética , Carcinomatose Meníngea/patologia , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/administração & dosagem , Quinazolinas/uso terapêutico , Deleção de Sequência , Resultado do TratamentoRESUMO
Central nervous system (CNS) involvement is a major complication of haematological and solid tumors with an incidence that ranges from 10% in solid malignances up to 25% in specific leukaemia or lymphoma subtypes. Cerebrospinal fluid (CSF) patterns are unspecific. Though CSF cytology has a high specificity (up to 95%), its sensitivity is generally less than 50% and no diagnostic gold standard marker is available, yet. New technologies such as flow cytometry, molecular genetics and newer biomarkers may improve diagnostic sensitivity and specificity, leading to the CNS involvement diagnosis, and consequently, to an effective prophylaxis and successful treatment.
O envolvimento do sistema nervoso central (SNC) é uma das maiores complicações das neoplasias de linhagem hematológica e dos tumores sólidos, com uma incidência que varia de 10% nestes últimos até 25% nas leucemias e subtipos de linfomas. Os padrões do líquido cefalorraquiano (LCR) nestes casos é inespecífico. Embora a citologia do LCR tenha uma alta especificidade (acima de 95%), sua sensibilidade é geralmente menor que 50%, e nenhum marcador biológico de padrão-ouro é disponível até o momento. Novas tecnologias, como a citologia de fluxo, a genética molecular e novos biomarcadores poderão aumentar a sensibilidade e especificidade no diagnóstico, levando ao diagnóstico de envolvimento do SNC, e consequentemente a profilaxia efetiva e tratamento bem sucedido.
Assuntos
Humanos , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Linfoma/líquido cefalorraquidiano , Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/secundário , Citometria de Fluxo , Linfoma/diagnóstico , Sensibilidade e EspecificidadeRESUMO
A fratura evolutiva é uma rara complicação que se observa geralmente na infância. Caracteriza-se por afastamento progressivo das bordas das fraturas, às vezes associado à formação de um cisto leptomeníngeo, também conhecido como cisto leptomeníngeo pós-traumático. De acordo com a literatura internacional, sua prevalência varia entre 0,03% e 1,6%. Analisamos a casuística de pacientes internados com traumatismo cranioencefálico no Hospital da Restauração de Recife (Brasil), um centro de referência em neurocirurgia pediátrica, no período de 1° de dezembro de 2000 a 30 de abril de 2008. O grupo de estudo compreendeu crianças de 0 a 14 anos. Durante essa investigação foram realizadas 19.758 admissões na emergência pediátrica por traumatismo cranioencefálico, e 74% foram admitidos da área metropolitana e 26% do interior do estado de Pernambuco. Foi observada fratura craniana em 6,3% dos casos, dos quais cinco crianças (menores de 3 anos) desenvolveram fratura evolutiva, representando 0,4% das fraturas de crânio e 0,02% dos traumatismos cranioencefálicos admitidos. Foi achada em todos os casos uma massa pulsátil, que apareceu em média no quarto mês após o trauma. As cinco crianças foram submetidas a tratamento cirúrgico, que compreendeu a ressecção do cisto leptomeníngeo e do tecido cerebral herniado, reparo do defeito dural e cranioplastia. A nossa experiência e a revisão bibliográfica mostram que crianças menores de 3 anos com história de traumatismo cranioencefálico e fratura de crânio apresentam risco de desenvolver fratura evolutiva. No entanto, sendo uma condição rara crianças com fratura de crânio menores de 3 anos, é obrigatório o acompanhamento clínico. Quando diagnosticado, o tratamento cirúrgico imediato é indicado para prevenir déficit neurológico.
Growing fracture is a rare complication that usually is observed in childhood. It is characterized by a progressive opening from the edges of fractures, sometimes associated with the formation of leptomeningeal cyst, also known as post-traumatic leptomeningeal cyst. According to the literature, its prevalence ranges from 0.03% to 1.6%. We analyzed a casuistic of patients hospitalized with head trauma at the Hospital da Restauração of Recife (Brazil), a referral center for pediatric neurosurgery, in the period from December 1st 2000 to April 30th, 2008. The study group consisted of children aged 0 to 14 years. During this research, were analyzed 19,758 emergency admissions for pediatric traumatic brain injury, which 74% were admitted to the metropolitan area and 26% were from the countryside, in the state of Pernambuco. Skull fracture was observed in 6.3% of cases, including 5 children under 3 years old, who developed growing fracture, constituting 0.4% of skull fractures and 0.02% of traumatic brain injury admitted. In all cases, it was found a pulsating mass that appeared in an average time in the 4th month after the trauma. The five children were submitted to surgical resection of the leptomeningeal cyst and of the herniated brain tissue, repair of dural defect and cranioplasty. Our experience and review of the literature show that children under 3 years old, with a history of traumatic brain injury and skull fracture, present at risk of developing a growing fracture. Even though, it is a rare condition, a clinical follow-up is mandatory for these children. When the growing fracture is diagnosed, an immediate surgical treatment is indicated to prevent neurologic deficit.