RESUMO
PATZ1-rearranged sarcomas are well-recognized tumors as part of the family of round cell sarcoma with EWSR1-non-ETS fusions. Whether PATZ1-rearranged central nervous system (CNS) tumors are a distinct tumor type is debatable. We thoroughly characterized a pediatric series of PATZ1-rearranged CNS tumors by chromosome microarray analysis (CMA), DNA methylation analysis, gene expression profiling and, when frozen tissue is available, optical genome mapping (OGM). The series consisted of 7 cases (M:F=1.3:1, 1-17 years, median 12). On MRI, the tumors were supratentorial in close relation to the lateral ventricles (intraventricular or iuxtaventricular), preferentially located in the occipital lobe. Two major histologic groups were identified: one (4 cases) with an overall glial appearance, indicated as "neuroepithelial" (NET) by analogy with the corresponding methylation class (MC); the other (3 cases) with a predominant spindle cell sarcoma morphology, indicated as "sarcomatous" (SM). A single distinct methylation cluster encompassing both groups was identified by multidimensional scaling analysis. Despite the epigenetic homogeneity, unsupervised clustering analysis of gene expression profiles revealed 2 distinct transcriptional subgroups correlating with the histologic phenotypes. Interestingly, genes implicated in epithelial-mesenchymal transition and extracellular matrix composition were enriched in the subgroup associated to the SM phenotype. The combined use of CMA and OGM enabled the identification of chromosome 22 chromothripsis in all cases suitable for the analyses, explaining the physical association of PATZ1 to EWSR1 or MN1. Six patients are currently disease-free (median follow-up 30 months, range 12-92). One patient of the SM group developed spinal metastases at 26 months from diagnosis and is currently receiving multimodal therapy (42 months). Our data suggest that PATZ1-CNS tumors are defined by chromosome 22 chromothripsis as causative of PATZ1 fusion, show peculiar MRI features (eg, relation to lateral ventricles, supratentorial frequently posterior site), and, although epigenetically homogenous, encompass 2 distinct histologic and transcriptional subgroups.
Assuntos
Cromotripsia , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Criança , Fatores de Transcrição/genética , Sarcoma/genética , Proteína EWS de Ligação a RNA/genética , Sistema Nervoso Central/patologia , Transcriptoma , Neoplasias de Tecidos Moles/genética , Proteínas Repressoras/genética , Fatores de Transcrição Kruppel-Like/genéticaRESUMO
Glioblastoma is the most common and aggressive primitive brain tumor in adults. Temozolomide (TMZ) administered daily with radiation therapy, followed by adjuvant TMZ has become the standard treatment. Although TMZ treatment has been considered to have a low toxicity profile, studies have noted the development of a severe myelosuppression, especially during the concomitant treatment; this toxicity may in some cases be prolonged and consequently treatment must be definitively discontinued. We analyzed two cases treated at our oncological center who developed severe and prolonged hematological toxicity during concomitant chemoradiotherapy treatment with TMZ. Hypothesizing that radiation therapy and daily TMZ could be the major causes of severe hematological toxicity during the concomitant phase, we decided to treat both patients with maintenance TMZ at the time of recovery of hematological values. Patients showed good tolerability without important myelosuppression. In conclusion, we suggest that glioblastoma patients with severe myelotoxicity during daily TMZ and radiation therapy be treated with maintenance TMZ at the time of blood value recovery.
Assuntos
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Doenças Hematológicas/etiologia , Temozolomida/administração & dosagem , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Neoplasias Encefálicas/patologia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Feminino , Glioblastoma/patologia , Humanos , Pessoa de Meia-Idade , Temozolomida/efeitos adversosAssuntos
Dermatoses Faciais/complicações , Fixação Ocular , Músculos Oculomotores/fisiopatologia , Esclerodermia Localizada/complicações , Estrabismo/etiologia , Criança , Quimioterapia Combinada , Dermatoses Faciais/diagnóstico , Dermatoses Faciais/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Músculos Oculomotores/diagnóstico por imagem , Prednisona/uso terapêutico , Esclerodermia Localizada/diagnóstico , Esclerodermia Localizada/tratamento farmacológico , Estrabismo/diagnóstico por imagem , Estrabismo/fisiopatologia , Resultado do TratamentoRESUMO
Prevalence of symptomatic central nervous system (CNS) metastases among patients with breast cancer ranges from 5% to 16%, although autoptic studies have reported prevalence rates of up to 30%. Solid brain tumours are the most common presentation in the CNS (85-95%), and they tend to arise at the grey-white matter junction with a distribution that is proportional to the regional cerebral blood flow. Descriptions of solitary intra-ventricular metastasis are very rare; to date no cases from breast cancer have been reported in the literature. We present the unusual case of a breast cancer patient who developed a solitary choroid plexus metastasis in the left lateral ventricle.
Assuntos
Neoplasias Encefálicas/secundário , Neoplasias da Mama/patologia , Carcinoma/patologia , Ventrículos Laterais/patologia , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Reduction of apparent diffusion coefficient (ADC) values in white matter is not always ischaemic in nature. METHODS: We retrospectively analysed our MRI records featuring reduced ADC values in the centrum semiovale without grey matter involvement or significant vasogenic oedema. RESULTS: Several conditions showed the aforementioned MR findings: moose-horn lesions on coronal images in X-linked Charcot-Marie-Tooth disease; small fronto-parietal lesions in Menkes disease; marked signal abnormalities in the myelinised regions in the acute neonatal form of maple syrup urine disease; strip-like involvement of the corpus callosum in glutaric aciduria type 1; persistent periventricular parieto-occipital abnormalities in phenylketonuria; diffuse signal abnormalities with necrotic evolution in global cerebral anoxia or after heroin vapour inhalation; almost completely reversible symmetric fronto-parietal lesions in methotrexate neurotoxicity; chain-like lesions in watershed ischaemia; splenium involvement that normalises in reversible splenial lesions or leads to gliosis in diffuse axonal injury. CONCLUSION: Neuroradiologists must be familiar with these features, thereby preventing misdiagnosis and inappropriate management.