Tumor embrionário raro do sistema nervoso central caracterizado por células embrionárias dispostas em rosetas multicamadas e exibindo um dos três padrões morfológicos: tumor embrionário com neuropilo abundante e rosetas verdadeiras, ependimoblastoma ou meduloepitelioma. Os tumores geralmente têm uma alteração C19MC ou (raramente) uma mutação DICER1 e correspondem ao grau IV da OMS. Estão localizados principalmente intracranianamente, raramente na medula espinhal, e commumente causam sinais e sintomas de pressão intracraniana elevada, às vezes convulsões e sinais neurológicos focais. A maioria dos casos ocorre em crianças durante os dois primeiros anos de vida.
Introdução
O que você precisa saber de cara
O tumor embrionário com rosetas multilaminadas (ETMR) é um tumor embrionário do sistema nervoso central. É considerado um tumor embrionário porque surge de células parcialmente diferenciadas ou ainda indiferenciadas desde o nascimento, geralmente células neuroepiteliais, que são células-tronco destinadas a se transformar em glia ou neurônios. Pode ocorrer em qualquer parte do cérebro e pode ter múltiplos locais de origem, com alta probabilidade de metástase através do líquido cefalorraquidiano (LCR). Metástases fora do sistema nervoso central foram relatadas, mas permanecem raras.
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Sinais e sintomas
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Genética e causas
O que está alterado no DNA e como passa nas famílias
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Extracranial teratoid medulloepithelioma: A pelvic observation with genetic and epigenetic findings.
In the latest version of the World Health Organization Classification (WHO) of Central Nervous System Tumors, the terminology "medulloepithelioma" has disappeared as a distinct tumor type in favor of "embryonal tumor with multilayered rosettes (ETMR)", characterized by frequent alterations of C19MC. However, medulloepithelioma persists in the current WHO classification of eye tumors, where two variants exist (teratoid and non-teratoid), harboring frequent DICER1 mutations. DNA-methylation profiling has demonstrated that ETMR and intraocular medulloepitheliomas represented two distinct methylation classes. Outside the CNS and the eye, exceptional observations of medulloepitheliomas have been reported, most of them before the genetic and epigenetic eras. Herein, we report a pediatric case of a presacral tumor classified as a teratoid medulloepithelioma with genetic and epigenetic charaterizations. Using DNA-methylation profiling analysis, the tumor was classified between ETMR, non C19MC-altered, and intra-ocular medulloepithelioma, arguing for a potential distinct cell origin, not represented in the current epigenetic classifiers.
DNA Methylation Profiling Classifies and Reveals Origin of Gynecologic Central Nervous System-Like Tumors.
Gynecologic neuroectodermal tumors either exhibit central nervous system (CNS) differentiation (CNS-like) or represent Ewing sarcoma (EWS), which lacks CNS features and harbors FET-ETS gene fusions. DNA methylation profiling reclassified CNS primitive neuroectodermal tumors into common CNS neoplasms or embryonal tumors with specific epigenetic/genetic characteristics. Its utility in classifying gynecologic neuroectodermal tumors is unknown. Whole-genome DNA methylation profiling was performed on 26 gynecologic neuroectodermal tumors (22 CNS-like tumors, 4 EWS) arising in the ovary, paratubal soft tissue, uterus, and vulva, which were classified by using sarcoma and CNS tumor DNA methylation classifiers. Sarcoma-related gene fusions were confirmed by fluorescence in situ hybridization or targeted RNA next-generation sequencing. Tumor-only whole-exome sequencing (WES) was performed in 13 cases. Copy number alterations and zygosity were inferred from DNA methylation array and WES data. Methylation abnormalities associated with imprinting were examined. The sarcoma methylation classifier identified EWS (n = 3) and high-grade endometrial stromal sarcoma (n = 1), confirmed by fluorescence in situ hybridization or next-generation sequencing detection of EWSR1 and YWHAE rearrangements, respectively. The remaining CNS-like tumors were classified by DNA methylation with positive/valid (n = 4), indeterminate (n = 9), and negative (n = 9) scores at the family level. Methylation subclasses included teratoma; embryonal tumor with multilayered rosettes, atypical; medulloblastoma, SHH-activated, subtype 3; medulloblastoma, group 3; intraocular medulloepithelioma; supratentorial ependymoma, ZFTA::RELA fused, subclass A; and diffuse pediatric-type high-grade glioma, MYCN subtype. Male biological sex was predicted in 54% of methylation-confirmed CNS-like tumors and none of the sarcomas. Among CNS-like tumors, copy number analyses identified genome-wide chromosomal gains and losses, and WES revealed genome-wide allelic imbalance suggestive of genome-wide duplications. Epigenetic imprinting analyses showed increased paternal or maternal imprinting signal across multiple chromosomes, suggesting uniparental duplication. DNA methylation profiling successfully classified gynecologic neuroectodermal tumors as known CNS tumors or sarcoma entities. Epigenetic and exomic studies indicate a male genome and increased maternal allelic contribution in CNS-like tumors, suggesting development via conception or chimerism.
Central Nervous System Embryonal Tumors.
Central nervous system (CNS) embryonal tumors are a subset of aggressive pediatric brain tumors, more frequently seen in infants and young children. They share an aggressive imaging appearance with frequent disseminated disease and guarded prognosis; however, patient age, tumor location, and imaging characteristics such as enhancement pattern and peritumoral edema can help with differential diagnosis. In this article, we have reviewed medulloblastoma, atypical teratoid rhabdoid tumor, embryonal tumor with multilayered rosettes as well as newly recognized CNS neuroblastoma, FOXR2-activated and CNS tumor with BCOR internal tandem duplication.
ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.
Embryonal tumor with multilayered rosettes (ETMR) is a lethal embryonal brain tumor entity. To investigate the intratumoral heterogeneity and cellular communication in the tumor microenvironment (TME), we analyze in this work single-cell RNA sequencing of about 250,000 cells of primary human and murine ETMR, in vitro cultures, and a 3D forebrain organoid model of ETMR, supporting the main findings with immunohistochemistry and spatial transcriptomics of human tumors. We characterize three distinct malignant ETMR subpopulations - RG-like, NProg-like and NB-like - positioned within a putative neurodevelopmental hierarchy. We reveal PDGFRβ+ pericytes as key communication partners in the TME, contributing to stem cell signaling through extracellular matrix-mediated interactions with tumor cells. PDGF signaling is upregulated in chemoresistant RG-like cells in vivo and plays a role in recruiting pericytes to ETMR TME by finalizing a signaling cascade which promotes the differentiation of non-malignant radial glia cells, derived from our 3D model, into pericyte-like cells. Selective PDGFR-inhibition blocked the lineage differentiation into pericytes in vitro and reduced the tumor cell population in vivo. Targeting ETMR-pericyte interactions in the TME presents a promising therapeutic approach.
Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.
Embryonal tumor with multilayered rosettes (ETMR) is a pediatric brain tumor with dismal prognosis. Characteristic alterations of the chromosome 19 microRNA cluster (C19MC) are observed in most ETMR; however, the ramifications of C19MC activation and the complex cellular architecture of ETMR remain understudied. Here we analyze 11 ETMR samples from patients using single-cell transcriptomics and multiplexed spatial imaging. We reveal a spatially distinct cellular hierarchy that spans highly proliferative neural stem-like cells and more differentiated neuron-like cells. C19MC is predominantly expressed in stem-like cells and controls a transcriptional network governing stemness and lineage commitment, as resolved by genome-wide analysis of microRNA-mRNA binding. Systematic analysis of receptor-ligand interactions between malignant cell types reveals fibroblast growth factor receptor and Notch signaling as oncogenic pathways that can be successfully targeted in preclinical models and in one patient with ETMR. Our study provides fundamental insights into ETMR pathobiology and a powerful rationale for more effective targeted therapies.
Publicações recentes
DICER1-Related Tumor Predisposition.
Extracranial teratoid medulloepithelioma: A pelvic observation with genetic and epigenetic findings.
🥉 Relato de casoYAP1::MAML2 fusion, a newly identified genetic anomaly in a posterior fossa infant tumor, associated with the methylation class "embryonal tumor with multilayered rosettes, non-C19MC-altered" in the Heidelberg central nervous system tumor classifier and "embryonal tumor with multilayered rosettes-DICER" in the NIH classifier.
DNA Methylation Profiling Classifies and Reveals Origin of Gynecologic Central Nervous System-Like Tumors.
Central Nervous System Embryonal Tumors.
📚 EuropePMC64 artigos no totalmostrando 94
Extracranial teratoid medulloepithelioma: A pelvic observation with genetic and epigenetic findings.
Virchows Archiv : an international journal of pathologyYAP1::MAML2 fusion, a newly identified genetic anomaly in a posterior fossa infant tumor, associated with the methylation class "embryonal tumor with multilayered rosettes, non-C19MC-altered" in the Heidelberg central nervous system tumor classifier and "embryonal tumor with multilayered rosettes-DICER" in the NIH classifier.
Acta neuropathologica communicationsDNA Methylation Profiling Classifies and Reveals Origin of Gynecologic Central Nervous System-Like Tumors.
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, IncCentral Nervous System Embryonal Tumors.
Neuroimaging clinics of North AmericaRare and aggressive: A case of embryonal tumor with multilayered rosettes (ETMR) in a young child.
Radiology case reportsOutcomes of Infants and Young Children With CNS Embryonal Tumors Using Pre-Irradiation Chemotherapy: A Decade Long Experience.
Cancer medicineETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.
Nature communicationsPhase 3 randomized trial of high-dose methotrexate for young children with high-risk embryonal brain tumors: A report from the Children's Oncology Group.
Neuro-oncologyCellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.
Nature cancerOutcomes following radiation therapy for embryonal tumor with multilayered rosettes (ETMR): results from the Pediatric Proton/Photon Consortium Registry (PPCR).
Journal of neuro-oncologyExploring Maintenance Therapy in Pediatric Embryonal Tumor With Multilayered Rosettes.
Journal of pediatric hematology/oncologyClinicopathologic and molecular characterization of primitive neuroectodermal tumors (PNET) in the female genital tract: a retrospective study of 8 cases.
Human pathologyEvaluating the efficacy of radiotherapy in patients with embryonal tumor with multilayered rosettes: A systematic review and meta-analysis.
Neuro-oncology practiceEmbryonal tumor with multilayered rosettes, DICER1-mutated, showing histologically unique neuronal differentiation after chemoradiotherapy.
Neuropathology : official journal of the Japanese Society of NeuropathologyPediatric skull base tumors: Clinical features and surgical outcomes; a single center retrospective study with a review of literature.
Brain & spineCerebrospinal fluid liquid biopsy by low-pass whole genome sequencing for clinical disease monitoring in pediatric embryonal tumors.
Neuro-oncology advancesDICER1-sarcomas of GYN tract: Expanding on an emerging entity.
Human pathology[Embryonal tumor with multilayered rosettes: a clinicopathological analysis of three cases].
Zhonghua bing li xue za zhi = Chinese journal of pathologyNon-C19MC-altered embryonal tumor with multilayered rosettes in a young woman with DICER1 syndrome: case report and review of the literature.
PathologicaGenetic mutation and immune infiltration in embryonal tumor with multilayered rosettes.
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryCase of embryonal tumor multilayered rosettes in a patient with neurofibromatosis type 1.
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Neurology IndiaIntegrated proteomics spotlight the proteasome as a therapeutic vulnerability in embryonal tumors with multilayered rosettes.
Neuro-oncologyMethylation-based Subclassifications of Embryonal Tumor with Multilayered Rosettes in Not Just Pediatric Brains.
Experimental neurobiologyEmbryonal tumor with multilayered rosettes arising from the internal auditory canal of an adult: Illustrative case with molecular investigations.
Neuropathology : official journal of the Japanese Society of NeuropathologyEmbryonal tumor with multilayered rosettes: Overview of diagnosis and therapy.
Neuro-oncology advancesMedulloblastomas, CNS embryonal tumors, and cerebellar mutism syndrome: advances in care and future directions.
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryEmbryonal Tumors of the Central Nervous System with Multilayered Rosettes and Atypical Teratoid/Rhabdoid Tumors.
Advances in experimental medicine and biologyCurrent Open Trials and Molecular Update for Pediatric Embryonal Tumors.
Pediatric neurosurgeryEmbryonal tumor with multilayered rosettes: Post-treatment maturation and implications for future therapy.
Cancer reports (Hoboken, N.J.)Efficient detection and monitoring of pediatric brain malignancies with liquid biopsy based on patient-specific somatic mutation screening.
Neuro-oncology[Imaging findings of supratentorial embryonal tumor with multilayered rosettes in children].
Zhonghua yi xue za zhiEmbryonal tumor with multilayered rosettes: a report of a rare case.
BJR case reportsClinical Management of Embryonal Tumor with Multilayered Rosettes: The CCMC Experience.
Children (Basel, Switzerland)Embryonal tumor with multilayered rosettes; rare pediatric CNS tumor. A case report and review of literature.
International journal of pediatrics & adolescent medicineMolecular classification and outcome of children with rare CNS embryonal tumors: results from St. Jude Children's Research Hospital including the multi-center SJYC07 and SJMB03 clinical trials.
Acta neuropathologicaSpectrum of paired-like homeobox 2b immunoexpression in pediatric brain tumors with embryonal morphology.
Pathology international[Embryonal tumor with multilayered rosettes (ETMR): case report and literature review].
Zhurnal voprosy neirokhirurgii imeni N. N. BurdenkoGerm cell tumors with neuroglial differentiation do not show molecular features akin to their central nervous system counterpart: experience from extra-gynecological sites.
Virchows Archiv : an international journal of pathologyPrognostic impact of the multimodal treatment approach in patients with C19MC-altered embryonal tumor with multilayered rosettes.
Journal of neurosurgery. PediatricsEmbryonal tumors in the WHO CNS5 classification: A Review.
Indian journal of pathology & microbiologyEmbryonal tumor with multilayered rosettes in a teenager.
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Neuro-oncologyEvaluation and Diagnosis of Central Nervous System Embryonal Tumors (Non-Medulloblastoma).
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology SocietyVorinostat and isotretinoin with chemotherapy in young children with embryonal brain tumors: A report from the Pediatric Brain Tumor Consortium (PBTC-026).
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Modern pathology : an official journal of the United States and Canadian Academy of Pathology, IncDICER1-associated malignancies mimicking germ cell neoplasms: Report of two cases and review of the literature.
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Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryA pediatric cerebral tumor with MN1 alteration and pathological features mimicking carcinoma metastasis: may the terminology "high grade neuroepithelial tumor with MN1 alteration" still be relevant?
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryClinicopathological characteristics and outcomes in embryonal tumor with multilayered rosettes: A decade long experience from a tertiary care centre in North India.
Annals of diagnostic pathologyRetrobulbar embryonal tumor with multilayered rosettes in a golden retriever dog.
Clinical case reportsEmbryonal Tumor With Multilayered Rosettes of the Parietooccipital Region: A Case Report.
Journal of pediatric hematology/oncologyPotential Importance of Early Focal Radiotherapy Following Gross Total Resection for Long-Term Survival in Children With Embryonal Tumors With Multilayered Rosettes.
Frontiers in oncologyC19MC amplification and expression of Lin28A and Olig2 in the classification of embryonal tumors of the central nervous system: A 14-year retrospective study from a tertiary care center.
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryHistopathologic and Molecular Features of Central Nervous System Embryonal Tumors for Integrated Diagnosis Reporting.
Surgical pathology clinicsTranscriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes.
GenesEmbryonal tumor with multilayered rosettes, C19MC-altered with sarcomatous differentiation: histopathologic and molecular characterization of one case.
Clinical neuropathologyETMR: a tumor entity in its infancy.
Acta neuropathologicaEmbryonal Tumors of the Central Nervous System: An Update.
Surgical pathology clinicsPontine Embryonal Tumor With Multilayered Rosettes: An Autopsy Case Exhibiting Extensive Posttreatment Glial and Neuronal Maturation.
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology SocietyEmbryonal tumor with multilayered rosettes, C19MC-altered (ETMR): a newly defined pediatric brain tumor.
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Pediatric blood & cancerMolecular pathology of tumors of the central nervous system.
Annals of oncology : official journal of the European Society for Medical OncologyIntegration of a Personalized Molecular Targeted Therapy into the Multimodal Treatment of Refractory Childhood Embryonal Tumor with Multilayered Rosettes (ETMR).
Case reports in oncologyApplications of molecular neuro-oncology - a review of diffuse glioma integrated diagnosis and emerging molecular entities.
Diagnostic pathologyTargeted radioimmunotherapy for embryonal tumor with multilayered rosettes.
Journal of neuro-oncologyAdvances in Diagnostic Immunohistochemistry for Primary Tumors of the Central Nervous System.
Advances in anatomic pathologyMedulloepithelioma with heterologous osteoid component: a case report and review of literature.
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryEmbryonal tumor with multilayered rosettes: illustrative case and review of the literature.
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryCentral Nervous System-type Neuroepithelial Tumors and Tumor-like Proliferations Developing in the Gynecologic Tract and Pelvis: Clinicopathologic Analysis of 23 Cases.
The American journal of surgical pathologyRare Brain Tumor in a Neonate.
Journal of medical ultrasoundEmbryonal Tumor with Multilayered Rosettes Presenting with Intermittent Third Nerve Palsy.
The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiquesEmbryonal Tumor with Multilayered Rosettes, C19MC-Altered: Clinical, Pathological, and Neuroimaging Findings.
Journal of neuroimaging : official journal of the American Society of NeuroimagingFour Levels of Diagnosis in the Rare Pediatric Embryonal Tumor of the CNS Called Embryonal Tumor with Multilayered Rosettes.
Radiographics : a review publication of the Radiological Society of North America, IncEmbryonal Tumors of the Central Nervous System: From the Radiologic Pathology Archives.
Radiographics : a review publication of the Radiological Society of North America, IncIncorporating Advances in Molecular Pathology Into Brain Tumor Diagnostics.
Advances in anatomic pathologyEmbryonal tumor with multilayered rosettes: Diagnosis on intra-operative squash smear.
Neuropathology : official journal of the Japanese Society of NeuropathologyA Congenital Case of Ependymoblastoma: A Rare and Aggressive Brain Tumor.
Journal of pediatric hematology/oncologyEmbryonal tumor with multilayered rosettes, C19MC-altered: Report of an extremely rare malignant pediatric central nervous system neoplasm.
SAGE open medical case reportsA Simplified Overview of World Health Organization Classification Update of Central Nervous System Tumors 2016.
Journal of neurosciences in rural practiceExtracranial extra-CNS spread of embryonal tumor with multilayered rosettes (ETMR): case series and systematic review.
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryLIN28A, a sensitive immunohistochemical marker for Embryonal Tumor with Multilayered Rosettes (ETMR), is also positive in a subset of Atypical Teratoid/Rhabdoid Tumor (AT/RT).
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryThe 2016 WHO Classification of Tumours of the Central Nervous System: The Major Points of Revision.
Neurologia medico-chirurgicaPreclinical drug screen reveals topotecan, actinomycin D, and volasertib as potential new therapeutic candidates for ETMR brain tumor patients.
Neuro-oncologyTargeted next-generation sequencing of pediatric neuro-oncology patients improves diagnosis, identifies pathogenic germline mutations, and directs targeted therapy.
Neuro-oncologyEmbryonal Tumor with Multilayered Rosettes in a 3-Year-Old Girl: Case Report.
Turkish neurosurgeryAtypical teratoid/rhabdoid tumors with multilayered rosettes in the pineal region.
Brain tumor pathologyOverexpression of Lin28b in Neural Stem Cells is Insufficient for Brain Tumor Formation, but Induces Pathological Lobulation of the Developing Cerebellum.
Cerebellum (London, England)[Clinicopathologic features of embryonal tumor with multilayered rosettes and gene analysis on chromosome 19q13.42].
Zhonghua bing li xue za zhi = Chinese journal of pathologyUncommon pediatric tumors of the posterior fossa: pathologic and molecular features.
Child's nervous system : ChNS : official journal of the International Society for Pediatric NeurosurgeryEmbryonal tumor with multilayered rosettes of the fourth ventricle: case report.
Journal of neurosurgery. PediatricsComparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities.
Neuropathology : official journal of the Japanese Society of NeuropathologyAssociações
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Referências e fontes
Bases de dados externas citadas neste artigo
Publicações científicas
Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.
- Extracranial teratoid medulloepithelioma: A pelvic observation with genetic and epigenetic findings.
- DNA Methylation Profiling Classifies and Reveals Origin of Gynecologic Central Nervous System-Like Tumors.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc· 2026· PMID 41285250mais citado
- Central Nervous System Embryonal Tumors.
- ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.
- Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions.
- DICER1-Related Tumor Predisposition.
- YAP1::MAML2 fusion, a newly identified genetic anomaly in a posterior fossa infant tumor, associated with the methylation class "embryonal tumor with multilayered rosettes, non-C19MC-altered" in the Heidelberg central nervous system tumor classifier and "embryonal tumor with multilayered rosettes-DICER" in the NIH classifier.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:656417(Orphanet)
- MONDO:0958119(MONDO)
- GARD:6352(GARD (NIH))
- Busca completa no PubMed(PubMed)
Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
