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Brain Pathology (Zurich, Switzerland) Apr 2024
PubMed: 38600765
DOI: 10.1111/bpa.13260 -
Advances and Technical Standards in... 2024Pediatric brain tumors are different to those found in adults in pathological type, anatomical site, molecular signature, and probable tumor drivers. Although these... (Review)
Review
Pediatric brain tumors are different to those found in adults in pathological type, anatomical site, molecular signature, and probable tumor drivers. Although these tumors usually occur in childhood, they also rarely present in adult patients, either as a de novo diagnosis or as a delayed recurrence of a pediatric tumor in the setting of a patient that has transitioned into adult services.Due to the rarity of pediatric-like tumors in adults, the literature on these tumor types in adults is often limited to small case series, and treatment decisions are often based on the management plans taken from pediatric studies. However, the biology of these tumors is often different from the same tumors found in children. Likewise, adult patients are often unable to tolerate the side effects of the aggressive treatments used in children-for which there is little or no evidence of efficacy in adults. In this chapter, we review the literature and summarize the clinical, pathological, molecular profile, and response to treatment for the following pediatric tumor types-medulloblastoma, ependymoma, craniopharyngioma, pilocytic astrocytoma, subependymal giant cell astrocytoma, germ cell tumors, choroid plexus tumors, midline glioma, and pleomorphic xanthoastrocytoma-with emphasis on the differences to the adult population.
Topics: Adult; Humans; Child; Brain Neoplasms; Astrocytoma; Medulloblastoma; Pituitary Neoplasms; Cerebellar Neoplasms
PubMed: 38592530
DOI: 10.1007/978-3-031-53578-9_5 -
Advances and Technical Standards in... 2024Ependymomas comprise biologically distinct tumor types with respect to age distribution, (epi)genetics, localization, and prognosis. Multimodal risk-stratification,... (Review)
Review
Ependymomas comprise biologically distinct tumor types with respect to age distribution, (epi)genetics, localization, and prognosis. Multimodal risk-stratification, including histopathological and molecular features, is essential in these biologically defined tumor types. Gross total resection (GTR), achieved with intraoperative monitoring and neuronavigation, and if necessary, second-look surgery, is the most effective treatment. Adjuvant radiation therapy is mandatory in high-risk tumors and in case of residual tumor. There is yet growing evidence that some ependymal tumors may be cured by surgery alone. To date, the role of chemotherapy is unclear and subject of current studies.Even though standard therapy can achieve reasonable survival rates for the majority of ependymoma patients, long-term follow-up still reveals a high probability of relapse in certain biological entities.With increasing knowledge of biologically distinct tumor types, risk-adapted adjuvant therapy gains importance. Beyond initial tumor control, and avoidance of therapy-induced morbidity for low-risk patients, intensified treatment for high-risk patients comprises another challenge. With identification of specific risk features regarding molecular alterations, targeted therapy may represent an option for individualized treatment modalities in the future.
Topics: Humans; Ependymoma; Age Distribution; Aggression; Brain Neoplasms; Combined Modality Therapy
PubMed: 38592527
DOI: 10.1007/978-3-031-53578-9_2 -
Acta Neuropathologica Communications Apr 2024A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial...
A novel methylation class, "neuroepithelial tumor, with PLAGL1 fusion" (NET-PLAGL1), has recently been described, based on epigenetic features, as a supratentorial pediatric brain tumor with recurrent histopathological features suggesting an ependymal differentiation. Because of the recent identification of this neoplastic entity, few histopathological, radiological and clinical data are available. Herein, we present a detailed series of nine cases of PLAGL1-fused supratentorial tumors, reclassified from a series of supratentorial ependymomas, non-ZFTA/non-YAP1 fusion-positive and subependymomas of the young. This study included extensive clinical, radiological, histopathological, ultrastructural, immunohistochemical, genetic and epigenetic (DNA methylation profiling) data for characterization. An important aim of this work was to evaluate the sensitivity and specificity of a novel fluorescent in situ hybridization (FISH) targeting the PLAGL1 gene. Using histopathology, immunohistochemistry and electron microscopy, we confirmed the ependymal differentiation of this new neoplastic entity. Indeed, the cases histopathologically presented as "mixed subependymomas-ependymomas" with well-circumscribed tumors exhibiting a diffuse immunoreactivity for GFAP, without expression of Olig2 or SOX10. Ultrastructurally, they also harbored features reminiscent of ependymal differentiation, such as cilia. Different gene partners were fused with PLAGL1: FOXO1, EWSR1 and for the first time MAML2. The PLAGL1 FISH presented a 100% sensitivity and specificity according to RNA sequencing and DNA methylation profiling results. This cohort of supratentorial PLAGL1-fused tumors highlights: 1/ the ependymal cell origin of this new neoplastic entity; 2/ benefit of looking for a PLAGL1 fusion in supratentorial cases of non-ZFTA/non-YAP1 ependymomas; and 3/ the usefulness of PLAGL1 FISH.
Topics: Child; Humans; Brain Neoplasms; Cell Cycle Proteins; Central Nervous System Neoplasms; Ependymoma; Glioma, Subependymal; In Situ Hybridization, Fluorescence; Supratentorial Neoplasms; Transcription Factors; Tumor Suppressor Proteins
PubMed: 38581034
DOI: 10.1186/s40478-023-01695-7 -
Journal of Neurosurgery. Pediatrics Apr 2024More than one-third of pediatric patients who undergo resection of intradural spine lesions develop progressive postoperative deformity, with as many as half of these...
OBJECTIVE
More than one-third of pediatric patients who undergo resection of intradural spine lesions develop progressive postoperative deformity, with as many as half of these patients subsequently requiring surgical fusion. Intradural spinal procedures with simultaneous instrumented fusion in children, however, are infrequently performed. Moreover, the rationale for patient selection, outcomes, and safety of this single-stage surgery in children has not been systematically investigated. In this study, the authors review the practice of simultaneous intradural spinal resection and instrumented fusion in pediatric patients and provide two representative case examples from their institution.
METHODS
The authors searched the PubMed and Embase databases and performed a systematic review following the PRISMA protocol. Original articles of pediatric patients (age ≤ 18 years) who underwent intradural spine surgery, regardless of pathology, with concomitant instrumented fusion and reported outcomes were included. An institutional database of all spinal operations with instrumented fusion performed in patients aged ≤ 18 years over a 3-year period was screened to identify those who underwent intradural spine surgery with concomitant fusion.
RESULTS
Nine patients (median age 12 years) from 6 studies who underwent intradural lesion resection and concomitant fusion met inclusion criteria. Among all 11 patients included, primary rationales for concomitant fusion were extensive bone removal (i.e., corpectomy or total facetectomy, 73%), concerns for deformity in the setting of multilevel laminectomy/laminoplasty (18%), and severe baseline deformity (9%). The most represented pathology was neurenteric cyst (55%) followed by schwannoma (18%). Myxopapillary ependymoma, granular cell tumor, and pilocytic astrocytoma each were seen in 1 case. Seven patients (64%) underwent an anterior-approach corpectomy, tumor resection, and fusion, while the remaining 4 patients (36%) underwent a posterior approach. All patients with at least 1 year of follow-up cases achieved bony fusion. CSF leak and new-onset neurological deficit each occurred in 9% (1/11).
CONCLUSIONS
The rationales for performing single-stage intradural resection and fusion in pediatric patients in studies to date include the presence of severe baseline deformity, large extent of bone resection, and multilevel laminectomy/laminoplasty across cervicothoracic or thoracolumbar junctions. As current literature involving this cohort is limited, more data are needed to determine when concomitant fusion in intradural resections is appropriate in pediatric patients and whether its routine implementation is safe or beneficial.
PubMed: 38579345
DOI: 10.3171/2024.1.PEDS23444 -
Annals of Diagnostic Pathology Jun 2024Ependymomas (EPNs) of the spinal region are a heterogeneous group of tumors that account for 17.6 % in adults. Four types have been recognized: subependymoma, spinal...
BACKGROUND
Ependymomas (EPNs) of the spinal region are a heterogeneous group of tumors that account for 17.6 % in adults. Four types have been recognized: subependymoma, spinal ependymoma (Sp-EPN), myxopapillary ependymoma (MPE), and Sp-EPN-MYCN amplified, each with distinct histopathological and molecular features.
METHODS
This study investigated the clinical and pathological characteristics and MYCN expression levels of 35 Sp-EPN and MPE cases diagnosed at a tertiary university hospital over a decade-long period.
RESULTS
Twenty-five cases were Sp-EPN and 10 cases were MPE, and were graded as WHO grade 2, except for 1 Sp-EPN case with grade 3 features. The most common symptoms were lower back pain and difficulty in walking. Radiology showed different tumor sizes and locations along the spinal cord, with MPEs exclusively in the lumbosacral region. Surgery was the main treatment, and gross total resection was achieved in all cases except for one. Immunohistochemistry showed low Ki-67 proliferation indices in all cases, and no MYCN expression. During follow-up, 3 (8.6 %) cases recurred and/or metastasized and 5 cases (14.3 %) died. No significant difference was found in disease-free survival or overall survival between Sp-EPN and MPE cases. However, 3 cases with grade 2 histology demonstrated recurrence and/or metastasis, despite the lack of MYCN expression.
CONCLUSION
Our results underscore the multifactorial nature of tumor aggressiveness in EPNs of the spinal region. This study enhances our knowledge of the clinical and pathological features of Sp-EPNs and MPEs and highlights the need for better diagnostic and prognostic markers in these rare tumors.
Topics: Humans; Ependymoma; Male; Female; Adult; Middle Aged; N-Myc Proto-Oncogene Protein; Spinal Cord Neoplasms; Young Adult; Aged; Adolescent; Biomarkers, Tumor; Immunohistochemistry
PubMed: 38555652
DOI: 10.1016/j.anndiagpath.2024.152299 -
Journal of Cancer Research and... Jan 2024Ependymomas account for 1-8% of overall brain tumors. They are most common at the age of 3-4 years. Their metastasis is very rare, and extraneural metastasis is even...
Ependymomas account for 1-8% of overall brain tumors. They are most common at the age of 3-4 years. Their metastasis is very rare, and extraneural metastasis is even more unusual. In this report, the ependymoma localized in the posterior fossa with metastasis into femoral diaphysis in a 27-year-old male patient, who was treated in 2001, is presented. As we did not have any other cases of patients having a brain and spinal tumor with extraneural metastases even after 21 years, until 2022, this case was found worthy of being presented. When the literature was examined, it was observed that there is still no standard treatment after surgery for ependymomas and their metastasis. Due to their rarity, the general treatment of extraneural metastasis of ependymomas is also under discussion. It is recommended that clinicians consider admitting patients with rare or hard-to-treat tumors to ongoing clinical trials.
Topics: Adult; Humans; Male; Brain Neoplasms; Ependymoma; Head; Spinal Cord Neoplasms; Spinal Neoplasms
PubMed: 38554364
DOI: 10.4103/jcrt.jcrt_1273_22 -
Zhurnal Voprosy Neirokhirurgii Imeni N.... 2024Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types. (Review)
Review
[Supratentorial neuroepithelial tumor with PLAGL1 gene fusion - a new type of morphologically variable pediatric brain neoplasm defined by a distinct DNA methylation class. A case report and literature review].
BACKGROUND
Methylation analysis has become a powerful diagnostic tool in modern neurooncology. This technique is valuable to diagnose new brain tumor types.
OBJECTIVE
To describe the MRI and histological pattern of neuroepithelial tumor with PLAGL1 gene fusion.
MATERIAL AND METHODS
We present a 6-year-old patient with small right frontal intraaxial tumor causing drug resistant epilepsy. Despite indolent preoperative clinical course and MRI features suggesting glioneuronal tumor, histological evaluation revealed characteristics of high-grade glioma, ependymoma and neuroblastoma.
RESULTS
Methylation analysis of tumor DNA confirmed a new type of a recently discovered neoplasm - neuroepithelial tumor with PLAGL1 fusion (NET PLAGL1). PCR confirmed fusion of PLAGL1 and EWSR1 genes. No seizures were observed throughout the follow-up period. There was no tumor relapse a year after surgery.
CONCLUSION
Methylation analysis in neurooncology is essential for unclear tumor morphology or divergence between histological and clinical data. In our case, this technique confirmed benign nature of tumor, and we preferred follow-up without unnecessary adjuvant treatment.
Topics: Child; Humans; Cell Cycle Proteins; DNA Methylation; Gene Fusion; Glioma; Neoplasms, Neuroepithelial; Supratentorial Neoplasms; Transcription Factors; Tumor Suppressor Proteins
PubMed: 38549412
DOI: 10.17116/neiro20248802162 -
Quantitative Imaging in Medicine and... Mar 2024Intracranial extraventricular ependymoma (IEE) and glioblastoma (GBM) may have similar imaging findings but different prognosis. This study aimed to develop and validate...
BACKGROUND
Intracranial extraventricular ependymoma (IEE) and glioblastoma (GBM) may have similar imaging findings but different prognosis. This study aimed to develop and validate a nomogram based on magnetic resonance imaging (MRI) Visually AcceSAble Rembrandt Images (VASARI) features for preoperatively differentiating IEE from GBM.
METHODS
The clinical data and the MRI-VASARI features of patients with confirmed IEE (n=114) and confirmed GBM (n=258) in a multicenter cohort were retrospectively analyzed. Predictive models for differentiating IEE from GBM were built using a multivariate logistic regression method. A nomogram was generated and the performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness.
RESULTS
The predictors identified in this study consisted of six VASARI features and four clinical features. Compared with the individual models, the combined model incorporating clinical and VASARI features had the highest area under the curve (AUC) value [training set: 0.99, 95% confidence interval (CI): 0.98-1.00; validation set: 0.97, 95% CI: 0.94-1.00] in comparison to the clinical model. The nomogram was well calibrated with significant clinical benefit according to the calibration curve and decision curve analyses.
CONCLUSIONS
The nomogram combining clinical and MRI-VASARI characteristics was robust for differentiating IEE from GBM preoperatively and may potentially assist in diagnosis and treatment of brain tumors.
PubMed: 38545063
DOI: 10.21037/qims-23-1148 -
Biomedicines Feb 2024Various types of brain tumors occur in both children and adults. These tumors manifest with different characteristics such as malignancy, cellular lineage, location of...
Various types of brain tumors occur in both children and adults. These tumors manifest with different characteristics such as malignancy, cellular lineage, location of origin, and genomic profile. Recently, immunotherapy, which manipulates immune cells in the tumor microenvironment (TME) to kill tumor cells, has attracted attention as a treatment strategy for tumors. Here, we analyzed the transcriptomic architecture of the brain tumor microenvironment to provide potential guidelines to overcome the therapeutic vulnerabilities to brain tumors. We decomposed the cellular populations of six brain tumor types (meningioma, pilocytic astrocytoma, ependymoma, medulloblastoma, glioblastoma, and lower-grade glioma) using publicly available microarray data and single-cell RNA sequencing (scRNA-seq) data. Interestingly, transcriptome-based immune cell profiling revealed that infiltrating immune cell types in the brain TME, particularly M2 macrophages, CD8+ T cells, and CD4+ T cells, could be distinguished by tumor type, malignancy, and location. scRNA-seq revealed differences in the proportions of dendritic and mural cells. Unsupervised clustering using immune-related genes divided all samples into two distinct clusters with different characteristics. In addition, immune subpopulations showed disparate reactions after anti-PD-1 therapy for glioblastoma. Our results unveiled the distinct TME across brain tumor types and provided a transcriptomic landscape. Our findings may contribute to realizing future precision medicine, providing a basic rationale for the therapeutics of brain tumors.
PubMed: 38540119
DOI: 10.3390/biomedicines12030506