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Acta Neuropathologica Mar 2022Tumors of the central nervous system (CNS) often display a wide morphologic spectrum that has, until recently, been the sole basis for tumor classification. The...
High-grade glioma with pleomorphic and pseudopapillary features (HPAP): a proposed type of circumscribed glioma in adults harboring frequent TP53 mutations and recurrent monosomy 13.
Tumors of the central nervous system (CNS) often display a wide morphologic spectrum that has, until recently, been the sole basis for tumor classification. The introduction of the integrated histomolecular diagnostic approach in CNS tumors has facilitated a classification system that is increasingly data-driven and with improved alignment to clinical outcome. Here, we report a previously uncharacterized glioma type (n = 31) using unsupervised clustering analysis of DNA methylation array data from approximately 14,000 CNS tumor samples. Histologic examination revealed circumscribed growth and morphologic similarities to pleomorphic xanthoastrocytoma (PXA), astroblastoma, ependymoma, polymorphous neuroepithelial tumor of the young (PLNTY), and IDH-wildtype glioblastoma (GBM). Median age (46.5 years) was significantly older than other circumscribed gliomas and younger than GBM. Dimensionality reduction with uniform manifold approximation and projection (UMAP) and hierarchical clustering confirmed a methylation signature distinct from known tumor types and methylation classes. DNA sequencing revealed recurrent mutations in TP53 (57%), RB1 (26%), NF1 (26%), and NF2 (14%). BRAF V600E mutations were detected in 3/27 sequenced cases (12%). Copy number analysis showed increased whole chromosome aneuploidy with recurrent loss of chromosome 13 (28/31 cases, 90%). CDKN2A/B deletion (2/31, 6%) and MGMT promoter methylation (1/31, 3%) were notably rare events. Most tumors showed features of a high-grade glioma, yet survival data showed significantly better overall survival compared to GBM (p < 0.0001). In summary, we describe a previously uncharacterized glioma of adults identified by a distinct DNA methylation signature and recurrent loss of chromosome 13.
Topics: Astrocytoma; Brain Neoplasms; Chromosomes, Human, Pair 13; Glioma; Humans; Middle Aged; Monosomy; Mutation; Tumor Suppressor Protein p53
PubMed: 35103816
DOI: 10.1007/s00401-022-02404-9 -
Acta Neuropathologica May 2023Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these...
Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.
Topics: Humans; Young Adult; Biomarkers, Tumor; Brain; Brain Neoplasms; Central Nervous System Neoplasms; Gene Fusion; Neoplasms, Neuroepithelial; Receptor Protein-Tyrosine Kinases; X-linked Nuclear Protein
PubMed: 36933012
DOI: 10.1007/s00401-023-02558-0 -
Balkan Medical Journal Jun 2020
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Agents, Immunological; Bevacizumab; Headache; Humans; Magnetic Resonance Imaging; Male; Neoplasms, Neuroepithelial; Radiotherapy; Temozolomide; Young Adult
PubMed: 32212579
DOI: 10.4274/balkanmedj.galenos.2020.2019.11.39 -
AJNR. American Journal of Neuroradiology Apr 2023Astroblastoma is a rare astrocytic glial neoplasm that affects mainly young girls, peaking between 10 and 30 years of age, with low- and high-grade manifestations....
Astroblastoma is a rare astrocytic glial neoplasm that affects mainly young girls, peaking between 10 and 30 years of age, with low- and high-grade manifestations. Imaging characteristics are well-described, but histopathologic and, more recently, molecular analysis is fundamental to establish the diagnosis, now based on alterations. We describe a case with typical imaging and histologic features of an -altered astroblastoma.
Topics: Female; Humans; Brain Neoplasms; Neoplasms, Neuroepithelial; Glioma; Astrocytoma; Radiology
PubMed: 36958802
DOI: 10.3174/ajnr.A7824 -
Neurologia (Barcelona, Spain) Apr 2010gliomatosis cerebri (GC) is a rare, diffusely growing glial tumour characterized by extensive brain infiltration. The diversity of histological subtype and grade on...
INTRODUCTION
gliomatosis cerebri (GC) is a rare, diffusely growing glial tumour characterized by extensive brain infiltration. The diversity of histological subtype and grade on presentation among different subjects, in addition to the usually poor response to treatment make GC an uncertain entity where many questions still remain unanswered. One article in this issue of NEUROLOGIA describes a series of 22 patients with GC, where clinical, therapeutic and outcome results are detailed.
DEVELOPMENT
clinical presentation of GC is non-specific and, although the neuroimage is characteristic, the spectrum of differential diagnosis is wide. Despite the fact that known prognostic factors in glioma also seem to be involved in GC, the heterogeneity of pathology and molecular findings on biopsy samples makes it difficult to characterise GC correctly. Therefore, variability of outcome and response to therapy is the rule. Evidence on therapeutic strategies is based on case-series. According to this, the optimal treatment is not well established. Part of current research is focused on identifying molecular predictor factors of response to chemotherapy.
CONCLUSIONS
the addition of chemotherapy in the classic treatment schedule based on radiotherapy seems to produce better responses in GC patients. However, the outcome of these patients remains poor with low survival rates. Phase III multi-centre trials to evaluate different therapeutic strategies in GC are essential. Further knowledge on the histological profile and molecular prognostic factors is also required. Patients should be stratified according to the prognostic factors identified.
Topics: Antineoplastic Agents; Brain Neoplasms; Diagnosis, Differential; Humans; Neoplasms, Neuroepithelial; Prognosis; Treatment Outcome
PubMed: 20492859
DOI: 10.1016/s0213-4853(10)70001-3 -
International Journal of Molecular... Jun 2022Renal medullary carcinoma (RMC) is a rare renal malignancy that has been associated with sickle hemoglobinopathies. RMC is aggressive, difficult to treat, and occurs... (Review)
Review
Renal medullary carcinoma (RMC) is a rare renal malignancy that has been associated with sickle hemoglobinopathies. RMC is aggressive, difficult to treat, and occurs primarily in adolescents and young adults of African ancestry. This cancer is driven by the loss of SMARCB1, a tumor suppressor seen in a number of primarily rare childhood cancers (e.g., rhabdoid tumor of the kidney and atypical teratoid rhabdoid tumor). Treatment options remain limited due in part to the limited knowledge of RMC biology. However, significant advances have been made in unraveling the biology of RMC, from genomics to therapeutic targets, over the past 5 years. In this review, we will present these advances and discuss what new questions exist in the field.
Topics: Adolescent; Carcinoma, Medullary; Carcinoma, Renal Cell; Child; Humans; Kidney Neoplasms; Neoplasms, Neuroepithelial; Rhabdoid Tumor; Young Adult
PubMed: 35806102
DOI: 10.3390/ijms23137097 -
Journal of Medical Case Reports Apr 2018Astroblastoma is a controversial and an extremely rare central nervous system neoplasm. Although its histogenesis has been clarified recently, controversies exist... (Review)
Review
BACKGROUND
Astroblastoma is a controversial and an extremely rare central nervous system neoplasm. Although its histogenesis has been clarified recently, controversies exist regarding its cellular origin and validity as a distinct entity. Because of its extreme rarity and because its common features are shared with other glial neoplasms, this tumor is prone to misdiagnosis and remains challenging not only in terms of diagnosis and classification but also in the subsequent management. This case report describes a new case of astroblastoma. It discusses clinical, radiologic, pathological, and therapeutic features and differential diagnosis of this rare neoplasm, with a review of the recent literature.
CASE PRESENTATION
We report the case of an 8-year-old Moroccan girl who presented with a 1-year history of epileptic seizure, headache, and decreased visual acuity. Cranial magnetic resonance imaging revealed a right occipito-temporal mass. A tumor resection was performed and histological examination combined with immunohistochemical study confirmed the diagnosis of low-grade astroblastoma.
CONCLUSIONS
Astroblastoma is a very rare primary brain tumor. Its diagnosis is often challenging because of the astroblastic aspects that can be found in astrocytic tumors, in ependymomas, and in non-neuroepithelial tumors. Considerable confusion surrounds its histogenesis and classification. The low incidence rate makes it difficult to conduct studies to examine tumor characteristics.
Topics: Brain Neoplasms; Child; Diagnosis, Differential; Female; Glioblastoma; Headache; Humans; Magnetic Resonance Imaging; Neoplasms, Neuroepithelial; Seizures
PubMed: 29678196
DOI: 10.1186/s13256-018-1623-1 -
Turkish Neurosurgery 2016Astroblastoma is a rare and distinct type of aggressive glial tumor for which there is much confusion regarding the diagnostic criteria. We present a case of... (Review)
Review
Astroblastoma is a rare and distinct type of aggressive glial tumor for which there is much confusion regarding the diagnostic criteria. We present a case of astroblastoma and review all relevant literature, aiming to discuss astroblastoma from the clinical, pathological, management, and prognostic points of view in an attempt to discover more of its secrets and to introduce a standard approach to its diagnosis and management.
Topics: Adult; Brain Neoplasms; Female; Humans; Male; Neoplasms, Neuroepithelial
PubMed: 27349390
DOI: 10.5137/1019-5149.JTN.9408-13.2 -
AJNR. American Journal of Neuroradiology Aug 2022Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors).... (Review)
Review
Glioneuronal tumors are characterized exclusively by neurocytic elements (neuronal tumors) or a combination of neuronal and glial features (mixed neuronal-glial tumors). Most of these tumors occur in young patients and are related to epilepsy. While ganglioglioma, dysembryoplastic neuroepithelial tumor, and desmoplastic infantile tumor are common glioneuronal tumors, anaplastic ganglioglioma, papillary glioneuronal tumor, rosette-forming glioneuronal tumor, gangliocytoma, and central neurocytoma are less frequent. Advances in immunohistochemical and molecular diagnostics have improved the characterization of these tumors and favored the description of variants and new subtypes, some not yet classified by the World Health Organization. Not infrequently, the histologic findings of biopsies of glioneuronal tumors simulate low-grade glial neoplasms; however, some imaging findings favor the correct diagnosis, making neuroimaging essential for proper management. Therefore, the aim of this review was to present key imaging, histopathology, immunohistochemistry, and molecular findings of glioneuronal tumors and their variants.
Topics: Humans; Child; Ganglioglioma; Neoplasms, Neuroepithelial; Central Nervous System Neoplasms; Brain Neoplasms; Neuroimaging
PubMed: 35512827
DOI: 10.3174/ajnr.A7465 -
Neuroradiology Aug 2021In addition to histology, genetic alteration is now required to classify many central nervous system (CNS) tumors according to the most recent World Health Organization... (Review)
Review
PURPOSE
In addition to histology, genetic alteration is now required to classify many central nervous system (CNS) tumors according to the most recent World Health Organization CNS tumor classification scheme. Although that is still not the case for classifying pediatric low-grade neuroepithelial tumors (PLGNTs), genetic and molecular features are increasingly being used for making treatment decisions. This approach has become a standard clinical practice in many specialized pediatric cancer centers and will likely be more widely practiced in the near future. This paradigm shift in the management of PLGNTs necessitates better understanding of how genetic alterations influence histology and imaging characteristics of individual PLGNT phenotypes.
METHODS
The complex association of genetic alterations with histology, clinical, and imaging of each phenotype of the extremely heterogeneous PLGNT family has been addressed in a holistic approach in this up-to-date review article. A new imaging stratification scheme has been proposed based on tumor morphology, location, histology, and genetics. Imaging characteristics of each PLGNT entity are also depicted in light of histology and genetics.
CONCLUSION
This article reviews the association of specific genetic alteration with location, histology, imaging, and prognosis of a specific tumor of the PLGNT family and how that information can be used for better imaging of these tumors.
Topics: Brain Neoplasms; Central Nervous System Neoplasms; Child; Glioma; Humans; Mutation; Neoplasms, Neuroepithelial; Prognosis
PubMed: 33779771
DOI: 10.1007/s00234-021-02691-1