RESUMEN
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.
Asunto(s)
Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Cromosomas Humanos Par 14/genética , Glioma/genética , Glioma/patología , Metilación de ADN , Femenino , Humanos , Masculino , Monosomía , Neurocitoma/genética , Neurocitoma/patología , Oligodendroglioma/genética , Oligodendroglioma/patologíaAsunto(s)
Ataxia/etiología , Linfoma de Células B de la Zona Marginal/diagnóstico por imagen , Imagen por Resonancia Magnética , Paraparesia/etiología , Compresión de la Médula Espinal/diagnóstico por imagen , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Vértebras Torácicas/diagnóstico por imagen , Anciano de 80 o más Años , Ataxia/patología , Ataxia/cirugía , Diagnóstico Diferencial , Humanos , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/cirugía , Masculino , Microcirugia , Examen Neurológico , Paraparesia/patología , Paraparesia/cirugía , Compresión de la Médula Espinal/patología , Compresión de la Médula Espinal/cirugía , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/cirugía , Vértebras Torácicas/patología , Vértebras Torácicas/cirugíaAsunto(s)
Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Trastornos Neurológicos de la Marcha/diagnóstico , Glioma/diagnóstico por imagen , Glioma/patología , Imagen por Resonancia Magnética/métodos , Ataxia/diagnóstico , Ataxia/etiología , Neoplasias Encefálicas/complicaciones , Niño , Diagnóstico Diferencial , Femenino , Trastornos Neurológicos de la Marcha/etiología , Glioma/complicaciones , HumanosRESUMEN
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.
Asunto(s)
Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Tratamiento Conservador/métodos , Epilepsia/etiología , Epilepsia/prevención & control , Procedimientos Neuroquirúrgicos/métodos , Neoplasias Encefálicas/diagnóstico , Terapia Combinada/métodos , Epilepsia/diagnóstico , Medicina Basada en la Evidencia , Humanos , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Complejo SIDA Demencia/patología , Hipocampo/patología , Inmunohistoquímica/métodos , Microglía/patología , Complejo SIDA Demencia/mortalidad , Complejo SIDA Demencia/fisiopatología , Adulto , Anciano , Autopsia , Femenino , Hipocampo/virología , Humanos , Masculino , Microglía/virología , Persona de Mediana EdadAsunto(s)
Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/cirugía , Epilepsia/etiología , Meduloblastoma/diagnóstico , Meduloblastoma/cirugía , Diagnóstico Diferencial , Epilepsia/diagnóstico , Epilepsia/prevención & control , Humanos , Imagen por Resonancia Magnética , Masculino , Meduloblastoma/complicaciones , Tomografía Computarizada por Rayos X , Adulto JovenAsunto(s)
Exoftalmia/diagnóstico , Exoftalmia/prevención & control , Imagen por Resonancia Magnética/métodos , Neoplasias del Nervio Óptico/patología , Neoplasias del Nervio Óptico/cirugía , Medios de Contraste , Exoftalmia/etiología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias del Nervio Óptico/complicacionesAsunto(s)
Calcinosis/diagnóstico , Calcinosis/cirugía , Lóbulo Frontal/cirugía , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/cirugía , Meningioma/diagnóstico , Meningioma/cirugía , Calcinosis/complicaciones , Femenino , Humanos , Imagen por Resonancia Magnética , Neoplasias Meníngeas/complicaciones , Meningioma/complicaciones , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del TratamientoAsunto(s)
Astrocitoma/complicaciones , Astrocitoma/diagnóstico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/etiología , Anciano de 80 o más Años , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/patología , Diagnóstico Diferencial , Femenino , Humanos , RadiografíaRESUMEN
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.
Asunto(s)
Análisis Mutacional de ADN , Eritromelalgia/tratamiento farmacológico , Eritromelalgia/genética , Canal de Sodio Activado por Voltaje NAV1.7/genética , Bloqueadores de los Canales de Sodio/uso terapéutico , Administración Oral , Aminas/efectos adversos , Aminas/uso terapéutico , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Niño , Ácidos Ciclohexanocarboxílicos/efectos adversos , Ácidos Ciclohexanocarboxílicos/uso terapéutico , Diagnóstico Diferencial , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Eritromelalgia/diagnóstico , Gabapentina , Humanos , Infusiones Intravenosas , Lidocaína/efectos adversos , Lidocaína/uso terapéutico , Masculino , Mexiletine/efectos adversos , Mexiletine/uso terapéutico , Nitroprusiato/efectos adversos , Nitroprusiato/uso terapéutico , Bloqueadores de los Canales de Sodio/efectos adversos , Resultado del Tratamiento , Vasodilatadores/efectos adversos , Vasodilatadores/uso terapéutico , Ácido gamma-Aminobutírico/efectos adversos , Ácido gamma-Aminobutírico/uso terapéuticoAsunto(s)
Neoplasias Encefálicas/patología , Epilepsia Tónico-Clónica/patología , Fórnix/patología , Glioma/patología , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Lóbulo Temporal/patología , Tomografía Computarizada por Rayos X , Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/cirugía , Proliferación Celular , Medios de Contraste/administración & dosificación , Diagnóstico Diferencial , Imagen de Difusión por Resonancia Magnética , Dominancia Cerebral/fisiología , Epilepsia Tónico-Clónica/cirugía , Fórnix/cirugía , Gadolinio , Glioma/cirugía , Humanos , Inmunohistoquímica , Invasividad Neoplásica , Lóbulo Occipital/patología , Lóbulo Occipital/cirugía , Giro Parahipocampal/patología , Giro Parahipocampal/cirugía , Lóbulo Temporal/cirugía , Tálamo/patología , Tálamo/cirugíaRESUMEN
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.