RESUMEN
Congenital intracranial meningiomas are rare lesions. We present a case of congenital intraventricular cystic meningioma, initially characterized with fetal MRI and confirmed postnatally with histopathology. To our knowledge, this is the first in vivo description of a congenital meningioma with fetal MRI. The fetal MRI was able to characterize the lesion as an atypical intraventricular mass which was separate from the choroid plexus, differentiating the mass from a choroid plexus neoplasm. An intraventricular location of the meningioma is more commonly described in pediatric than in adult patients. Meningioma should be considered in the differential for an intraventricular congenital lesion, and fetal MRI is advocated for lesion characterization.
Asunto(s)
Neoplasias del Plexo Coroideo , Neoplasias Meníngeas , Meningioma , Adulto , Niño , Plexo Coroideo/patología , Humanos , Imagen por Resonancia Magnética , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/patología , Meningioma/cirugíaRESUMEN
Subependymal giant cell astrocytoma (SEGA) is a World Health Organization (WHO) grade I tumor most commonly seen in the context of the underlying tuberous sclerosis complex (TSC). SEGA in the absence of TSC is exceedingly rare. We report the youngest known case of SEGA in the absence of genetic or phenotypic evidence of TSC with a 10-year follow-up. We discuss the literature surrounding isolated SEGA including an approach to diagnosis, management, and prognosis.
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Astrocitoma , Neoplasias Encefálicas , Esclerosis Tuberosa , Astrocitoma/complicaciones , Astrocitoma/diagnóstico por imagen , Neoplasias Encefálicas/diagnóstico por imagen , Humanos , Pronóstico , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/diagnóstico por imagenRESUMEN
AIMS: Extravascular migratory metastasis (EVMM) is a potential mechanism of tumour spread reported most extensively in cutaneous melanoma. It has not been described previously in gynaecological malignancies. We describe EVMM in four gynaecological carcinosarcomas. METHODS AND RESULTS: Extravascular migratory metastasis was observed in an ovarian carcinosarcoma during routine diagnostic assessment. Twenty-three additional, randomly selected gynaecological carcinosarcomas (11 tubo-ovarian and 12 endometrial) were examined retrospectively and EVMM was identified in three of these. Other than the index case, EVMM was a focal finding, identified in 12-18% of slides. The malignant cells demonstrating EVMM appeared sarcomatoid and were distributed abluminally, partly or completely surrounding the endothelium. Affected vessels often showed mural fibrin deposition. Immunohistochemistry for α-smooth muscle actin (SMA), CD31, CD34, D2-40, laminin and type IV collagen was performed on the EVMM-positive cases. The perivascular malignant cells showed more consistent SMA and laminin immunoreactivity than the non-vascular tumour elements. CONCLUSIONS: Extravascular migratory metastasis is a hitherto unrecognized mechanism of tumour spread in gynaecological carcinosarcomas. The perivascular tumour cells appear to adopt a pericytic phenotype, and this may represent a specific pattern of epithelial-mesenchymal transition. Further studies with pericyte-specific immunohistological markers may better demonstrate the presence and possible prognostic significance of EVMM in gynaecological tumours.
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Carcinosarcoma/patología , Carcinosarcoma/secundario , Neoplasias de los Genitales Femeninos/patología , Actinas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino , Antígenos CD34/metabolismo , Carcinosarcoma/metabolismo , Colágeno Tipo IV/metabolismo , Neoplasias Endometriales/patología , Transición Epitelial-Mesenquimal , Neoplasias de las Trompas Uterinas/patología , Femenino , Neoplasias de los Genitales Femeninos/irrigación sanguínea , Neoplasias de los Genitales Femeninos/metabolismo , Humanos , Inmunohistoquímica , Laminina/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica/patología , Metástasis de la Neoplasia/patología , Neoplasias Ováricas/patología , Pericitos/patología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Estudios RetrospectivosRESUMEN
Introduction: Ependymomas (EPN) are the third most common malignant brain cancer in children. Treatment strategies for pediatric EPN have remained unchanged over recent decades, with 10-year survival rates stagnating at just 67% for children aged 0-14 years. Moreover, a proportion of patients who survive treatment often suffer long-term neurological side effects as a result of therapy. It is evident that there is a need for safer, more effective treatments for pediatric EPN patients. There are ten distinct subgroups of EPN, each with their own molecular and prognostic features. To identify and facilitate the testing of new treatments for EPN, in vivo laboratory models representative of the diverse molecular subtypes are required. Here, we describe the establishment of a patient-derived orthotopic xenograft (PDOX) model of posterior fossa A (PFA) EPN, derived from a metastatic cranial lesion. Methods: Patient and PDOX tumors were analyzed using immunohistochemistry, DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. Results: Both patient and PDOX tumors classified as PFA EPN by methylation profiling, and shared similar histological features consistent with this molecular subgroup. RNA sequencing revealed that gene expression patterns were maintained across the primary and metastatic tumors, as well as the PDOX. Copy number profiling revealed gains of chromosomes 7, 8 and 19, and loss of chromosomes 2q and 6q in the PDOX and matched patient tumor. No clinically significant single nucleotide variants were identified, consistent with the low mutation rates observed in PFA EPN. Overexpression of EZHIP RNA and protein, a common feature of PFA EPN, was also observed. Despite the aggressive nature of the tumor in the patient, this PDOX was unable to be maintained past two passages in vivo. Discussion: Others who have successfully developed PDOX models report some of the lowest success rates for EPN compared to other pediatric brain cancer types attempted, with loss of tumorigenicity not uncommon, highlighting the challenges of propagating these tumors in the laboratory. Here, we discuss our collective experiences with PFA EPN PDOX model generation and propose potential approaches to improve future success in establishing preclinical EPN models.
RESUMEN
DNA methylation array profiling for classifying pediatric central nervous system (CNS) tumors is a valuable adjunct to histopathology. However, unbiased prospective and interlaboratory validation studies have been lacking. The AIM BRAIN diagnostic trial involving 11 pediatric cancer centers in Australia and New Zealand was designed to test the feasibility of routine clinical testing and ran in parallel with the Molecular Neuropathology 2.0 (MNP2.0) study at Deutsches Krebsforschungszentrum (German Cancer Research Center). CNS tumors from 269 pediatric patients were prospectively tested on Illumina EPIC arrays, including 104 cases co-enrolled on MNP2.0. Using MNP classifier versions 11b4 and 12.5, we report classifications with a probability score ≥0.90 in 176 of 265 (66.4%) and 213 of 269 (79.2%) cases, respectively. Significant diagnostic information was obtained in 130 of 176 (74%) for 11b4, and 12 of 174 (7%) classifications were discordant with histopathology. Cases prospectively co-enrolled on MNP2.0 gave concordant classifications (99%) and score thresholds (93%), demonstrating excellent test reproducibility and sensitivity. Overall, DNA methylation profiling is a robust single workflow technique with an acceptable diagnostic yield that is considerably enhanced by the extensive subgroup and copy number profile information generated by the platform. The platform has excellent test reproducibility and sensitivity and contributes significantly to CNS tumor diagnosis.
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Neoplasias del Sistema Nervioso Central , Metilación de ADN , Niño , Humanos , Australia , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/genética , Metilación de ADN/genética , Nueva Zelanda , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Muscular polyarteritis nodosa where disease is isolated to skeletal muscle is a rare and often poorly recognised clinical entity. Patients typically present with fever and severe muscle pain limiting ability to ambulate without rise in creatine kinase. Often there is a significant delay between presentation and diagnosis, which requires histological confirmation. Musculoskeletal MRI is a sensitive investigation that can lead to timely biopsy and improve diagnostic yield. Early diagnosis of this condition is essential as patients typically respond favourably to corticosteroid treatment. Here we report 4 cases of muscular polyarteritis nodosa and review the reported literature.
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Músculo Esquelético/patología , Mialgia/etiología , Poliarteritis Nudosa/diagnóstico , Adulto , Anciano , Antiinflamatorios , Antirreumáticos/administración & dosificación , Femenino , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Extremidad Inferior/diagnóstico por imagen , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Poliarteritis Nudosa/tratamiento farmacológico , Poliarteritis Nudosa/fisiopatologíaRESUMEN
Radiation-induced glioma (RIG) is a highly aggressive brain cancer arising as a consequence of radiation therapy. We report a case of RIG that arose in the brain stem following treatment for paediatric medulloblastoma, and the development and characterisation of a matched orthotopic patient-derived xenograft (PDX) model (TK-RIG915). Patient and PDX tumours were analysed using DNA methylation profiling, whole genome sequencing (WGS) and RNA sequencing. While initially thought to be a diffuse intrinsic pontine glioma (DIPG) based on disease location, results from methylation profiling and WGS were not consistent with this diagnosis. Furthermore, clustering analyses based on RNA expression suggested the tumours were distinct from primary DIPG. Additional gene expression analysis demonstrated concordance with a published RIG expression profile. Multiple genetic alterations that enhance PI3K/AKT and Ras/Raf/MEK/ERK signalling were discovered in TK-RIG915 including an activating mutation in PIK3CA, upregulation of PDGFRA and AKT2, inactivating mutations in NF1, and a gain-of-function mutation in PTPN11. Additionally, deletion of CDKN2A/B, increased IDH1 expression, and decreased ARID1A expression were observed. Detection of phosphorylated S6, 4EBP1 and ERK via immunohistochemistry confirmed PI3K pathway and ERK activation. Here, we report one of the first PDX models for RIG, which recapitulates the patient disease and is molecularly distinct from primary brain stem glioma. Genetic interrogation of this model has enabled the identification of potential therapeutic vulnerabilities in this currently incurable disease.
RESUMEN
Sporadic late onset nemaline myopathy (SLONM) is a rare, intractable acquired myopathy that is characterised by progressive muscle weakness and the presence of nemaline rods in myofibres. Unlike the congenital form of nemaline myopathy (NM), there are only few case reports and series on SLONM in the scientific literature. We present a case report of SLONM in a 62-year-old male from a rural town in Western Australia, without any of the conditions often associated with SLONM such as monoclonal gammopathy of uncertain significance or HIV infection. SLONM should be considered in the differential diagnosis of progressive proximal muscle weakness in an adult.