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Brain Pathology (Zurich, Switzerland) Jul 2021Assess the contribution of preoperative MRI data in improving grading of adult astrocytomas reclassified according to the WHO 2016 and cIMPACT-NOW update 3....
Prognostic relevance of adding MRI data to WHO 2016 and cIMPACT-NOW updates for diffuse astrocytic tumors in adults. Working toward the extended use of MRI data in integrated glioma diagnosis.
Assess the contribution of preoperative MRI data in improving grading of adult astrocytomas reclassified according to the WHO 2016 and cIMPACT-NOW update 3. Retrospective unicentric cohort study of 679 adult patients treated for newly diagnosed diffuse astrocytic and oligodendroglial tumors (January 2006-December 2016). We first systematically compared radiological (contrast enhancement present [CE+] vs. absent [CE-]) and histopathological findings (microvascular proliferation present [MPV+] vs. absent [MPV-]) to validate whether this comparing step of neoangiogenesis represents an efficient method to appreciate the representativity of the tumoral sampling. We focused on 629 cases of astrocytomas for radio-histological integrated analyses. In 598 cases (95.1%), neoangiogenesis evaluated by MRI or histology (CE+/MPV+ or CE-/MPV-) was identical. For the CE+/MPV- and CE-/MPV+ groups (23 cases), the radio-histological face-to-face evaluation allowed us to assess that for 13 cases (56.5%) the reason for this discrepancy was an undersampled tumor. We analyzed the group of CE+/MPV- (n = 8) and CE-/MPV+ (n = 2) in verified image-guided tumoral samples. Finally, we identified three new prognostic subgroups for molecular glioblastomas: (1) "non-representative sampling" (n = 9), (2) "Non neoangiogenic glioblastoma at the time of diagnosis, without contrast enhancement and microvascular proliferation" (n = 8), and (3) "contrast enhancing glioblastoma but without microvascular proliferation in a representative sample" (n = 4). Neoangiogenesis processes should be assessed to improve the prognosis accuracy of the current integrated diagnosis. We suggest adding imaging analyses during the neuropathological analysis of astrocytomas in adults.
Topics: Adult; Aged; Aged, 80 and over; Astrocytoma; Brain Neoplasms; Cohort Studies; Female; Glioblastoma; Glioma; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Oligodendroglioma; Prognosis; World Health Organization
PubMed: 33336392
DOI: 10.1111/bpa.12929 -
Journal of Comparative Pathology Oct 2019Two cases of high-grade glioma comprising sheets of oligodendroglial cells multifocally disrupted by regions of remarkable neuronal differentiation are described. These...
Two cases of high-grade glioma comprising sheets of oligodendroglial cells multifocally disrupted by regions of remarkable neuronal differentiation are described. These tumours morphologically resemble 'oligodendroglioma with ganglioglioma-like maturation', a rare tumour of man, but appear to be phenotypically more aggressive. Neuronal markers (synaptophysin, neuron-specific enolase and βIII-tubulin) effectively highlight neuronal elements within these tumours and could potentially help to further investigate the prevalence and biological significance of neuronal differentiation in canine oligodendroglioma.
Topics: Animals; Biomarkers; Brain Neoplasms; Cell Differentiation; Dog Diseases; Dogs; Histocytochemistry; Male; Neurons; Oligodendroglia; Oligodendroglioma; Phosphopyruvate Hydratase; Synaptophysin; Tubulin
PubMed: 31690408
DOI: 10.1016/j.jcpa.2019.08.003 -
Asian Pacific Journal of Cancer... Aug 2020Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of...
BACKGROUND
Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas.
METHODS
In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records.
RESULTS
Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival.
CONCLUSIONS
IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia.
.Topics: Adult; Asian People; Biomarkers, Tumor; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Glioma; Humans; Indonesia; Isocitrate Dehydrogenase; Male; Mutation; Prognosis; Promoter Regions, Genetic; Prospective Studies; Retrospective Studies; Survival Rate; Tumor Suppressor Proteins
PubMed: 32856857
DOI: 10.31557/APJCP.2020.21.8.2287 -
Acta Neuropathologica Communications Dec 2020Demyelinated lesions in human pons observed after osmotic shifts in serum have been referred to as central pontine myelinolysis (CPM). Astrocytic damage, which is...
Demyelinated lesions in human pons observed after osmotic shifts in serum have been referred to as central pontine myelinolysis (CPM). Astrocytic damage, which is prominent in neuroinflammatory diseases like neuromyelitis optica (NMO) and multiple sclerosis (MS), is considered the primary event during formation of CPM lesions. Although more data on the effects of astrocyte-derived factors on oligodendrocyte precursor cells (OPCs) and remyelination are emerging, still little is known about remyelination of lesions with primary astrocytic loss. In autopsy tissue from patients with CPM as well as in an experimental model, we were able to characterize OPC activation and differentiation. Injections of the thymidine-analogue BrdU traced the maturation of OPCs activated in early astrocyte-depleted lesions. We observed rapid activation of the parenchymal NG2 OPC reservoir in experimental astrocyte-depleted demyelinated lesions, leading to extensive OPC proliferation. One week after lesion initiation, most parenchyma-derived OPCs expressed breast carcinoma amplified sequence-1 (BCAS1), indicating the transition into a pre-myelinating state. Cells derived from this early parenchymal response often presented a dysfunctional morphology with condensed cytoplasm and few extending processes, and were only sparsely detected among myelin-producing or mature oligodendrocytes. Correspondingly, early stages of human CPM lesions also showed reduced astrocyte numbers and non-myelinating BCAS1 oligodendrocytes with dysfunctional morphology. In the rat model, neural stem cells (NSCs) located in the subventricular zone (SVZ) were activated while the lesion was already partially repopulated with OPCs, giving rise to nestin progenitors that generated oligodendroglial lineage cells in the lesion, which was successively repopulated with astrocytes and remyelinated. These nestin stem cell-derived progenitors were absent in human CPM cases, which may have contributed to the inefficient lesion repair. The present study points to the importance of astrocyte-oligodendrocyte interactions for remyelination, highlighting the necessity to further determine the impact of astrocyte dysfunction on remyelination inefficiency in demyelinating disorders including MS.
Topics: Adult; Aged; Animals; Antidiuretic Agents; Astrocytes; Cell Differentiation; Cell Lineage; Deamino Arginine Vasopressin; Demyelinating Diseases; Disease Models, Animal; Female; Humans; Lateral Ventricles; Male; Middle Aged; Myelin Sheath; Myelinolysis, Central Pontine; Neoplasm Proteins; Nestin; Neural Stem Cells; Oligodendrocyte Precursor Cells; Oligodendroglia; Rats; Sodium Chloride
PubMed: 33357244
DOI: 10.1186/s40478-020-01105-2 -
Acta Neuropathologica Communications Jun 2020Diffuse leptomeningeal glioneuronal tumor (DLGNT) was introduced, for the first time, as a provisional entity in the 2016 WHO classification of central nervous system...
Diffuse leptomeningeal glioneuronal tumor (DLGNT) was introduced, for the first time, as a provisional entity in the 2016 WHO classification of central nervous system tumors. DLGNT mainly occur in children and characterized by a widespread leptomeningeal growth occasionally associated with intraspinal tumor nodules, an oligodendroglial-like cytology, glioneuronal differentiation and MAP-Kinase activation associated with either solitary 1p deletion or 1p/19q codeletion in the absence of IDH mutation.We report here two unexpected DLGNTs adult cases, characterized by a unique supratentorial circumscribed intraparenchymal tumor without leptomeningeal involvement in spite of long follow-up. In both cases, the diagnosis of DLGNT was made after DNA-methylation profiling which demonstrated that one case belonged to the DLGNT class whereas the other remained not classifiable but showed on CNV the characteristic genetic findings recorded in DLGNT. Both cases harbored 1p/19q codeletion associated with KIAA1549:BRAF fusion in one case and with BRAF V600E and PIK3CA E545A mutations, in the other.Our study enlarges the clinical and molecular spectrum of DLGNTs, and points out that the terminology of DLGNTs is not fully appropriate since some cases could have neither diffuse growth nor leptomeningeal dissemination. This suggests that DLGNTs encompass a wide spectrum of tumors that has yet to be fully clarified.
Topics: Adult; Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Meningeal Neoplasms; Mutation; Oligodendroglioma; Proto-Oncogene Proteins B-raf
PubMed: 32605662
DOI: 10.1186/s40478-020-00978-7 -
Cancer Science Oct 2020Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3-K27M mutations,...
Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3-K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma-tailored 48-gene next-generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma-tailored 48-gene NGS panel for detecting 1p/19q codeletion and mutations in IDH1/2, TP53, PTEN, PDGFRA, NF1, RB1, CDKN2A/B, CDK4, and the TERT promoter (TERTp). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 IDH-wildtype glioblastomas. Within these IDH-wildtype glioblastomas, 33 samples (58.9%) showed a mutation in TERTp. Notably, PDGFRA mutations and their amplification were more commonly seen in TERTp-wildtype glioblastomas (43%) than in TERTp-mutant glioblastomas (6%) (P = .001). Hierarchical molecular classification of IDH-wildtype glioblastomas revealed 3 distinct groups of IDH-wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA, amplification of CDK4 and PDGFRA, homozygous deletion of CDKN2A/B, and absence of TERTp mutations. This cluster was significantly associated with older age (P = .021), higher Ki-67 score (P = .007), poor prognosis (P = .012), and a periventricular tumor location. We report the development of a glioma-tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of IDH- and TERTp-wildtype glioblastomas with frequent PDGFRA alterations.
Topics: Adult; Aged; Aged, 80 and over; Female; Glioblastoma; High-Throughput Nucleotide Sequencing; Humans; Isocitrate Dehydrogenase; Male; Middle Aged; Neoplasm Proteins; Promoter Regions, Genetic; Receptor, Platelet-Derived Growth Factor alpha; Telomerase
PubMed: 32748499
DOI: 10.1111/cas.14597 -
Folia Neuropathologica 2021Oligodendrocyte transcriptional factor-2 (Olig2) is an essential marker for oligodendrocytes expression. We aimed to explore the expression of Olig2 in different glial...
AIM OF THE STUDY
Oligodendrocyte transcriptional factor-2 (Olig2) is an essential marker for oligodendrocytes expression. We aimed to explore the expression of Olig2 in different glial neoplasms and to investigate if diffuse Olig2 expression can replace 1p19q co-deletion for the diagnosis of oligodendroglioma.
MATERIAL AND METHODS
Olig2 was performed on 53 samples of different glial neoplasms using immunohistochemistry (IHC). 1p/19q deletions were investigated using fluorescence in situ hybridization (FISH).
RESULTS
Olig2 labelling of different glial neoplasms revealed various expressions, in which 26 tumours showed diffuse expression (≥ 60%) and 23 tumours showed partial focal expression (< 50%). Four tumours showed no expression. Of the 26 tumours, 6 oligodendrogliomas had 1p19q co-deletion and the remaining 3 oligodendrogliomas showed no co-deletion. Three non-oligodendroglial tumours were found to have 19q deletion. The FISH of the remaining tumours (14/26) showed no aberrations. There was no significant difference in the final diagnosis by using 1p19q co-deletion test among glial neoplasms with diffuse Olig2 expression (p = 0.248).
CONCLUSIONS
Olig2 marker cannot be used as an alternative diagnostic method for 1p19q co-deletion to distinguish oligodendrogliomas from other glial neoplasms. Although some glial tumours showed diffuse Olig2 expression, 1p19q co-deletion testing is the best diagnostic method.
Topics: Brain Neoplasms; Chromosome Deletion; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Glioma; Humans; In Situ Hybridization, Fluorescence; Oligodendrocyte Transcription Factor 2; Oligodendroglia; Oligodendroglioma
PubMed: 35114775
DOI: 10.5114/fn.2021.112562 -
Acta Neuropathologica Jul 2021The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by...
The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced β-catenin binding resulting in increased cytosolic and nuclear β-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/β-catenin signaling.
Topics: Adenoma; Aniline Compounds; Animals; Antibody Diversity; Antigens, CD; Brain Neoplasms; Cadherins; Carcinoma; DNA, Neoplasm; Gene Knock-In Techniques; Genetic Variation; HEK293 Cells; Humans; Neoplasms, Neuroepithelial; Oligodendroglioma; Protein Kinase Inhibitors; Purines; Rats; Rats, Sprague-Dawley; Whole Genome Sequencing
PubMed: 33929593
DOI: 10.1007/s00401-021-02307-1 -
Polish Journal of Pathology : Official... 2022A diffuse leptomeningeal glioneuronal tumours (DLGNT) are very rare tumours of the central nervous system, typically characterized by enhancement of subarachnoid...
A diffuse leptomeningeal glioneuronal tumours (DLGNT) are very rare tumours of the central nervous system, typically characterized by enhancement of subarachnoid space with cystic lesions, diffuse leptomeningeal infiltration, and no primary mass. We report an atypical clinical presentation of DLGNT. A 48-year-old male was admitted to hospital with symptoms of ischaemic stroke. Magnetic resonance imaging of the head revealed contrast enhancement of the meninges and other parts of the brain. A stereotactic frame biopsy was performed on the patient, which revealed the DLGNT. Diffuse leptomeningeal glioneuronal tumours are mostly seen in individuals less than 18 years old and are characterized by slow growth and low-grade histological appearance. Diffuse leptomeningeal glioneuronal tumours can be aggressive in adults.
Topics: Male; Humans; Adult; Middle Aged; Adolescent; Brain Ischemia; Stroke; Central Nervous System Neoplasms; Meningeal Neoplasms; Magnetic Resonance Imaging
PubMed: 36946275
DOI: 10.5114/pjp.2022.125822 -
Indian Journal of Cancer 2023Mature cystic teratoma of the ovary is the most common type of germ cell tumor. It constitutes approximately 20% of all ovarian neoplasms. As a rare occurrence, however,...
Mature cystic teratoma of the ovary is the most common type of germ cell tumor. It constitutes approximately 20% of all ovarian neoplasms. As a rare occurrence, however, several types of benign and malignant tumours developing secondarily in dermoid cysts have been reported. Those of central nervous origin are almost exclusively gliomas of astrocytic, ependymal or oligodendroglial lineage. Choroid plexus tumors are unusual intracranial tumors which comprised of only 0.4-0.6% of all brain tumors. These are neuroectodermal in origin and similar in structure to a normal choroid plexus in the form of multiple papillary fronds mounted on a well vascularized connective tissue stroma. The present case report highlights the presence of a choroid plexus tumor in a mature cystic teratoma of the ovary in a 27-year-old woman who came for safe confinement and cesarean section.
Topics: Pregnancy; Humans; Female; Adult; Papilloma, Choroid Plexus; Cesarean Section; Ovarian Neoplasms; Teratoma
PubMed: 36861717
DOI: 10.4103/ijc.IJC_1038_19