RESUMO
AIMS: DNA methylation-based central nervous system (CNS) tumour classification has identified numerous molecularly distinct tumour types, and clinically relevant subgroups among known CNS tumour entities that were previously thought to represent homogeneous diseases. Our study aimed at characterizing a novel, molecularly defined variant of glioneuronal CNS tumour. PATIENTS AND METHODS: DNA methylation profiling was performed using the Infinium MethylationEPIC or 450 k BeadChip arrays (Illumina) and analysed using the 'conumee' package in R computing environment. Additional gene panel sequencing was also performed. Tumour samples were collected at the German Cancer Research Centre (DKFZ) and provided by multinational collaborators. Histological sections were also collected and independently reviewed. RESULTS: Genome-wide DNA methylation data from >25 000 CNS tumours were screened for clusters separated from established DNA methylation classes, revealing a novel group comprising 31 tumours, mainly found in paediatric patients. This DNA methylation-defined variant of low-grade CNS tumours with glioneuronal differentiation displays recurrent monosomy 14, nuclear clusters within a morphology that is otherwise reminiscent of oligodendroglioma and other established entities with clear cell histology, and a lack of genetic alterations commonly observed in other (paediatric) glioneuronal entities. CONCLUSIONS: DNA methylation-based tumour classification is an objective method of assessing tumour origins, which may aid in diagnosis, especially for atypical cases. With increasing sample size, methylation analysis allows for the identification of rare, putative new tumour entities, which are currently not recognized by the WHO classification. Our study revealed the existence of a DNA methylation-defined class of low-grade glioneuronal tumours with recurrent monosomy 14, oligodendroglioma-like features and nuclear clusters.
Assuntos
Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/patologia , Cromossomos Humanos Par 14/genética , Glioma/genética , Glioma/patologia , Metilação de DNA , Feminino , Humanos , Masculino , Monossomia , Neurocitoma/genética , Neurocitoma/patologia , Oligodendroglioma/genética , Oligodendroglioma/patologiaAssuntos
Ataxia/etiologia , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Imageamento por Ressonância Magnética , Paraparesia/etiologia , Compressão da Medula Espinal/diagnóstico por imagem , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Idoso de 80 Anos ou mais , Ataxia/patologia , Ataxia/cirurgia , Diagnóstico Diferencial , Humanos , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Microcirurgia , Exame Neurológico , Paraparesia/patologia , Paraparesia/cirurgia , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/cirurgia , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/patologia , Vértebras Torácicas/cirurgiaAssuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Transtornos Neurológicos da Marcha/diagnóstico , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância Magnética/métodos , Ataxia/diagnóstico , Ataxia/etiologia , Neoplasias Encefálicas/complicações , Criança , Diagnóstico Diferencial , Feminino , Transtornos Neurológicos da Marcha/etiologia , Glioma/complicações , HumanosRESUMO
BACKGROUND: Among the tumors associated with chronic epilepsy, dysembryoplastic neuroepithelial tumor and ganglioglioma are the most common besides angiocentric glioma, pleomorphic xanthoastrocytoma and pilocytic astrocytoma. These tumors are usually considered as being benign. OBJECTIVE: To determine the best conservative and surgical treatment of tumors associated with epilepsy. MATERIAL AND METHODS: This article presents case reports of malignant transformation of a dysembryoplastic neuroepithelial tumor and of a tumor initially diagnosed as a ganglioglioma based on magnetic resonance imaging (MRI) criteria. Description of references in the literature on epilepsy surgery and the neuro-oncology of epilepsy-associated tumors. RESULTS: In the case of the initially histopathologically diagnosed dysembryoplastic neuroepithelial tumor, a malignant transformation occurred 5 years after incomplete resection. The differentiation from a glioblastoma was possible through the analysis of the methylation profile. In another case a tumor assumed to be a ganglioglioma showed an increase in size after 6 years. Initial histopathological results revealed a glioblastoma. The analysis of the methylation profile suggested the diagnosis of an anaplastic pleomorphic xanthoastrocytoma and as a differential diagnosis an anaplastic ganglioglioma. Tumor progress correlated with the worsening of seizures. CONCLUSION: Recent studies have shown that in the treatment of predominantly benign epilepsy-associated tumors neuro-oncological aspects should also be taken into account in addition to the epileptological considerations. In the case of malignant transformation epigenetic screening (methylation profiles) can help to classify the tumor entity more precisely.
Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/terapia , Tratamento Conservador/métodos , Epilepsia/etiologia , Epilepsia/prevenção & controle , Procedimentos Neurocirúrgicos/métodos , Neoplasias Encefálicas/diagnóstico , Terapia Combinada/métodos , Epilepsia/diagnóstico , Medicina Baseada em Evidências , Humanos , Resultado do TratamentoRESUMO
OBJECTIVES: HIV infection affects the central nervous system (CNS), frequently causing cognitive impairment. Hippocampal injury impedes the ability to transfer information into memory. Therefore, we aimed to examine neuronal injury and repair in the hippocampal formation in HIV encephalopathy. METHODS: We compared neuropathological findings in 14 autopsy cases after death from systemic complications of HIV infection and in 15 age-matched HIV-negative control cases after sudden death from nonneurological causes using immunohistochemistry. RESULTS: The density of apoptotic granule cells in the dentate gyrus was higher in HIV-infected than in control cases (P = 0.048). Proliferation of neural progenitor cells in the dentate gyrus was increased in HIV infection (P = 0.028), whereas the density of recently generated TUC-4 [TOAD (turned on after division)/Ulip/CRMP family 4]-expressing neurons in this region was not significantly elevated in HIV-infected cases (P = 0.13). HIV infection caused microglial activation and astrocytosis in the neocortex and hippocampal formation. Conversely, we were unable to detect more pronounced axonal injury in HIV-infected than in control cases. CONCLUSIONS: As in other infections involving the CNS, apoptosis of hippocampal neurons accompanied by microglial activation and astrocytosis is a prominent feature of HIV encephalopathy. The regenerative potential, assessed using the density of young neurons in the hippocampal dentate gyrus, in HIV infection appears to be lower than in acute bacterial meningitis and septic encephalitis.
Assuntos
Complexo AIDS Demência/patologia , Hipocampo/patologia , Imuno-Histoquímica/métodos , Microglia/patologia , Complexo AIDS Demência/mortalidade , Complexo AIDS Demência/fisiopatologia , Adulto , Idoso , Autopsia , Feminino , Hipocampo/virologia , Humanos , Masculino , Microglia/virologia , Pessoa de Meia-IdadeAssuntos
Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/cirurgia , Epilepsia/etiologia , Meduloblastoma/diagnóstico , Meduloblastoma/cirurgia , Diagnóstico Diferencial , Epilepsia/diagnóstico , Epilepsia/prevenção & controle , Humanos , Imageamento por Ressonância Magnética , Masculino , Meduloblastoma/complicações , Tomografia Computadorizada por Raios X , Adulto JovemAssuntos
Exoftalmia/diagnóstico , Exoftalmia/prevenção & controle , Imageamento por Ressonância Magnética/métodos , Neoplasias do Nervo Óptico/patologia , Neoplasias do Nervo Óptico/cirurgia , Meios de Contraste , Exoftalmia/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias do Nervo Óptico/complicaçõesAssuntos
Calcinose/diagnóstico , Calcinose/cirurgia , Lobo Frontal/cirurgia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico , Meningioma/cirurgia , Calcinose/complicações , Feminino , Humanos , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/complicações , Meningioma/complicações , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Resultado do TratamentoAssuntos
Astrocitoma/complicações , Astrocitoma/diagnóstico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiologia , Idoso de 80 Anos ou mais , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologia , Diagnóstico Diferencial , Feminino , Humanos , RadiografiaRESUMO
Erythromelalgia is a rare disorder characterized by recurrent pain attacks, swelling and redness in the distal extremities. The primary forms of the disorder are caused by mutations in voltage-gated sodium channels. Treatment is difficult and controlled therapeutic studies offer little to no guidance. We report on a 12-year-old boy and his first occurrence of primary erythromelalgia. Genetic findings for mutations in the SCN9A gene, which encodes for the α-subunit of sodium channel NaV1.7, were negative. Although initial treatment with sodium nitroprusside was ineffective, subsequent medication with lidocaine and mexiletine, in combination with gabapentin, was successful. Despite negative findings for mutations in the sodium channels, the use of sodium channel blockers should be considered in these patients.
Assuntos
Análise Mutacional de DNA , Eritromelalgia/tratamento farmacológico , Eritromelalgia/genética , Canal de Sódio Disparado por Voltagem NAV1.7/genética , Bloqueadores dos Canais de Sódio/uso terapêutico , Administração Oral , Aminas/efeitos adversos , Aminas/uso terapêutico , Analgésicos/efeitos adversos , Analgésicos/uso terapêutico , Criança , Ácidos Cicloexanocarboxílicos/efeitos adversos , Ácidos Cicloexanocarboxílicos/uso terapêutico , Diagnóstico Diferencial , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Eritromelalgia/diagnóstico , Gabapentina , Humanos , Infusões Intravenosas , Lidocaína/efeitos adversos , Lidocaína/uso terapêutico , Masculino , Mexiletina/efeitos adversos , Mexiletina/uso terapêutico , Nitroprussiato/efeitos adversos , Nitroprussiato/uso terapêutico , Bloqueadores dos Canais de Sódio/efeitos adversos , Resultado do Tratamento , Vasodilatadores/efeitos adversos , Vasodilatadores/uso terapêutico , Ácido gama-Aminobutírico/efeitos adversos , Ácido gama-Aminobutírico/uso terapêuticoAssuntos
Neoplasias Encefálicas/patologia , Epilepsia Tônico-Clônica/patologia , Fórnice/patologia , Glioma/patologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Lobo Temporal/patologia , Tomografia Computadorizada por Raios X , Biomarcadores Tumorais/análise , Neoplasias Encefálicas/cirurgia , Proliferação de Células , Meios de Contraste/administração & dosagem , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética , Dominância Cerebral/fisiologia , Epilepsia Tônico-Clônica/cirurgia , Fórnice/cirurgia , Gadolínio , Glioma/cirurgia , Humanos , Imuno-Histoquímica , Invasividade Neoplásica , Lobo Occipital/patologia , Lobo Occipital/cirurgia , Giro Para-Hipocampal/patologia , Giro Para-Hipocampal/cirurgia , Lobo Temporal/cirurgia , Tálamo/patologia , Tálamo/cirurgiaRESUMO
This article presents the case of a 10-month-old baby girl with an atypical teratoid/rhabdoid tumor. The differential diagnosis relied on the findings from magnetic resonance with T1 and T2-weighted imaging as well as histological and immunohistochemical methods. The characteristics of the possible candidate lesions considered for the differential diagnosis are described.