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Case Reports in Oncology 2024Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting...
INTRODUCTION
Diffuse leptomeningeal glioneuronal tumor (DLGNT), a new addition to the 2016 World Health Organization (WHO) classification, is a rare childhood neoplasm presenting with disseminated leptomeningeal enhancement and an occasional intraparenchymal mass. Diagnosis is often impeded by infectious/immunological differentials, necessitating a biopsy to confirm the diagnosis. We report an adult male with DLGNT without hydrocephalus, which is rare in patients with cerebellar masses.
CASE PRESENTATION
A 56-year-old man presented with headaches, vertigo, diplopia, impaired hearing, and gait imbalance over 6 months. Magnetic resonance imaging showed a cystic right cerebellar mass with its leptomeningeal dissemination but without hydrocephalus. Cerebrospinal fluid analysis revealed elevated proteins with CD56-positive tumor cells. Cerebellar lesion biopsy verified the diagnosis of DLGNT (WHO Grade 3) with fusion and 1p deletion. Radiotherapy was prematurely aborted due to clinical deterioration. The patient was subsequently discharged to palliative home care and lost to follow-up.
CONCLUSION
We conducted the first review of all 34 adult DLGNT cases, including ours (one of the oldest), hitherto published in the literature. The majority presented with signs and symptoms of increased intracranial pressure. 52.0% of adult DLGNT patients were alive at follow-up. DLGNT should be considered in the differential diagnoses of diffuse leptomeningeal enhancement in imaging. Further studies comparing pediatric and adult subgroups of DLGNT are needed to evaluate histopathological prognosticators and standardize therapy for both subpopulations.
PubMed: 38404404
DOI: 10.1159/000536400 -
Neurosurgical Review Jan 2024The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to...
OBJECTIVE
The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors.
MATERIAL AND METHODS
One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature.
RESULTS
All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002).
CONCLUSION
Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics.
Topics: Humans; Neoplasm Recurrence, Local; Endoscopy; Glioma; Cerebral Cortex; Necrosis
PubMed: 38265724
DOI: 10.1007/s10143-024-02286-3 -
European Journal of Radiology Feb 2024To evaluate the feasibility of a multimodal approach involving dynamic contrast-enhanced (DCE) perfusion imaging and diffusion kurtosis imaging (DKI) in the preoperative...
Improved diagnostic confidence and tumor type prediction in adult-type diffuse glioma by multimodal imaging including DCE perfusion and diffusion kurtosis mapping - A standardized multicenter study.
BACKGROUND AND PURPOSE
To evaluate the feasibility of a multimodal approach involving dynamic contrast-enhanced (DCE) perfusion imaging and diffusion kurtosis imaging (DKI) in the preoperative imaging of brain tumors in a multicenter setting, and to evaluate the effect on diagnostic confidence and accuracy for tumor grade and type prediction.
MATERIALS AND METHODS
One hundred and thirty-three patients with brain tumors were imaged in six hospitals with a standardized multimodal protocol. Standard imaging and six parameter maps derived from DCE and DKI sequences were reviewed off-site by two independent readers. Image quality and diagnostic confidence were evaluated in qualitative analyses. Quantitative analyses were performed to assess diagnostic accuracy and the performance of DKI and DCE parameters for tumor grade differentiation and molecular tumor type determination.
RESULTS
Standardized acquisition of DCE and DKI maps was feasible with excellent image quality. Diagnostic confidence was significantly improved from 85 % to 96 % (p = 0.0005) by additional review of the DCE and DKI maps. The combination of mean kurtosis and CBV was particularly advantageous for differentiating low-grade and high-grade glioma, oligodendroglial vs. astrocytic, and IDH1/2 wild type vs. mutated tumors.
CONCLUSION
A multimodal imaging approach with DCE and DKI improves diagnostic confidence and yields higher diagnostic accuracy for predicting tumor grade and type in adult-type glioma.
Topics: Adult; Humans; Glioma; Brain Neoplasms; Diffusion Tensor Imaging; Perfusion; Multimodal Imaging; Diffusion Magnetic Resonance Imaging
PubMed: 38218066
DOI: 10.1016/j.ejrad.2024.111293 -
Nature Communications Nov 2023Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations....
Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53::lsl-MYCN mice. All mice developed aggressive forebrain tumors early in their lifetime that mimic human HGG-MYCN regarding histology, DNA methylation, and gene expression. Single-cell RNA sequencing revealed a high intratumoral heterogeneity with neuronal and oligodendroglial lineage signatures. High-throughput drug screening using both mouse and human tumor cells finally indicated high efficacy of Doxorubicin, Irinotecan, and Etoposide as possible therapy options that children with HGG-MYCN might benefit from.
Topics: Humans; Child; Mice; Animals; N-Myc Proto-Oncogene Protein; Neuroblastoma; Disease Models, Animal; Glioma; Mutation; Gene Amplification
PubMed: 38001143
DOI: 10.1038/s41467-023-43564-w -
Nature Reviews. Neuroscience Dec 2023Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of... (Review)
Review
Experience sculpts brain structure and function. Activity-dependent modulation of the myelinated infrastructure of the nervous system has emerged as a dimension of adaptive change during childhood development and in adulthood. Myelination is a richly dynamic process, with neuronal activity regulating oligodendrocyte precursor cell proliferation, oligodendrogenesis and myelin structural changes in some axonal subtypes and in some regions of the nervous system. This myelin plasticity and consequent changes to conduction velocity and circuit dynamics can powerfully influence neurological functions, including learning and memory. Conversely, disruption of the mechanisms mediating adaptive myelination can contribute to cognitive impairment. The robust effects of neuronal activity on normal oligodendroglial precursor cells, a putative cellular origin for many forms of glioma, indicates that dysregulated or 'hijacked' mechanisms of myelin plasticity could similarly promote growth in this devastating group of brain cancers. Indeed, neuronal activity promotes the pathogenesis of many forms of glioma in preclinical models through activity-regulated paracrine factors and direct neuron-to-glioma synapses. This synaptic integration of glioma into neural circuits is central to tumour growth and invasion. Thus, not only do neuron-oligodendroglial interactions modulate neural circuit structure and function in the healthy brain, but neuron-glioma interactions also have important roles in the pathogenesis of glial malignancies.
Topics: Humans; Neurons; Oligodendroglia; Myelin Sheath; Neuroglia; Glioma
PubMed: 37857838
DOI: 10.1038/s41583-023-00744-3 -
Journal of Cancer Research and... 2023Gliomas are the most common primary intracranial tumors. The current World Health Organization (WHO) classification of central nervous system tumors recommends...
INTRODUCTION
Gliomas are the most common primary intracranial tumors. The current World Health Organization (WHO) classification of central nervous system tumors recommends integrated histo-molecular diagnosis of gliomas. However, molecular testing is not available in even most of the advanced centers of our country, and histopathology aided with immunohistochemistry (IHC) is still widely used for diagnosis. Immunohistochemical markers such as iso-citrate dehydrogenase1 (IDH1) and Alpha Thalassemia/Mental Retardation Syndrome X-linked (ATRX) can be reliably used for the correct diagnosis, prognosis, and treatment of gliomas.
AIM
We aimed to develop a diagnostic algorithm by integrating morphology, IDH1, and ATRX status of gliomas seen in our institute for 1 year.
SETTINGS AND DESIGN
Analytical cross-sectional study.
MATERIALS AND METHODS
This study included 60 histopathologically confirmed cases of astrocytic (n = 51) and oligodendroglial tumors (n = 9). Clinical, radiological, and histopathological features were noted and tumor grades assigned according to the WHO recommendations. IDH1 and ATRX mutation status was evaluated using IHC. The tumors were divided into three molecular groups on the basis of their IDH1 and ATRX mutation status: (1) Group 1: IDH1 negative and ATRX positive, (2) Group 2: IDH1 positive and ATRX positive, (3) Group 3: IDH1 positive and ATRX negative.
RESULTS
The mean age of presentation was 45.0 ± 15.8 years with a male-to-female ratio of 2:1. Seizures, headache, and hemiparesis were the most common modes of presentation. The tumor subtypes studied were glioblastoma (n = 32), anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 6), pilocytic astrocytoma (n = 6), and anaplastic oligodendroglioma (n = 3). IDH1 mutation was present in 26 cases including anaplastic astrocytoma (n = 7), diffuse astrocytoma (n = 6), oligodendroglioma (n = 5), secondary glioblastoma (n = 5), and anaplastic oligodendroglioma (n = 3). ATRX mutation, i. e., loss of ATRX was observed in 17 cases including diffuse astrocytoma (n = 5), anaplastic astocytoma (n = 5), anaplastic oligodendroglioma (n = 3), oligodendroglioma (n = 3), and secondary glioblastoma (n = 1). All six cases of pilocytic astrocytoma were negative for IDH1 and ATRX mutation. There were 34 patients in Group 1 (IDH1- and ATRX +), nine cases in Group 2 (IDH1 + and ATRX +), and 17 patients in Group 3 (IDH1 + and ATRX-).
CONCLUSION
Diagnosis of gliomas should be based on a detailed clinicoradiological and histopathological assessment, followed by genotypic characterization. Evaluation for IDH1and ATRX status has both diagnostic and prognostic value as it helps in differentiating gliomas from reactive gliosis, primary glioblastoma from secondary glioblastoma, and pilocytic astrocytoma (WHO grade I) from diffuse astrocytoma (WHO grade II). Tumors with IDH1 mutations have a better outcome than those with wild-type IDH. IHC can serve as a useful surrogate to conventional molecular tests in resource-constrained settings. By devising an algorithm based on morphological and IHC features, we were able to stratify gliomas into three prognostic subgroups.
Topics: Humans; Male; Female; Adult; Middle Aged; Oligodendroglioma; Glioblastoma; Cross-Sectional Studies; X-linked Nuclear Protein; Glioma; Astrocytoma; Brain Neoplasms; Mutation; Prognosis; Citrates; Citric Acid; Isocitrate Dehydrogenase; Algorithms
PubMed: 37470575
DOI: 10.4103/jcrt.jcrt_102_21 -
Brain Pathology (Zurich, Switzerland) Jan 2024The tumor showed extensive microcalcifications and cells with oval, nuclei and a clear perinuclear halo (A), positive immunostaining for OLIG-2 (B), GFAP (C), and CD34...
The tumor showed extensive microcalcifications and cells with oval, nuclei and a clear perinuclear halo (A), positive immunostaining for OLIG-2 (B), GFAP (C), and CD34 (D), and intermingled Neu-N-positive neurons (E). FISH revealed multiple signals for the centromere of chromosome 7 (gains) (green probe) and the EGFR locus (red probe) (F, left), and a single signal for the centromere of chromosome 10 (loss) (F, right).
Topics: Humans; Brain Neoplasms; Microtubule-Associated Proteins; Glioma; Oligodendroglia; Calcinosis
PubMed: 37409721
DOI: 10.1111/bpa.13187 -
Clinical Cancer Research : An Official... Dec 2023Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during...
PURPOSE
Isocitrate dehydrogenase (IDH)-mutant gliomas are usually treated with radiotherapy and chemotherapy, which increases the risk for neurocognitive sequelae during patients' most productive years. We report our experience using off-label first-in-class mutant IDH1 inhibitor ivosidenib and its impact on tumor volume in IDH-mutant gliomas.
EXPERIMENTAL DESIGN
We retrospectively analyzed patients ages ≥18 years with radiation/chemotherapy-naïve, mutant IDH1, nonenhancing, radiographically active, grade 2/3 gliomas, and ≥2 pretreatment and ≥2 on-treatment ivosidenib MRIs. T2/FLAIR-based tumor volumes, growth rates, and progression-free survival (PFS) were analyzed. log-linear mixed-effect modeling of growth curves adjusted for grade, histology, and age was performed.
RESULTS
We analyzed 116 MRIs of 12 patients [10 males, median age 46 years (range: 26-60)]: 8 astrocytomas (50% grade 3) and 4 grade 2 oligodendrogliomas. Median on-drug follow-up was 13.2 months [interquartile range (IQR): 9.7-22.2]. Tolerability was 100%. A total of 50% of patients experienced ≥20% tumor volume reduction on-treatment and absolute growth rate was lower during treatment (-1.2 ± 10.6 cc/year) than before treatment (8.0 ± 7.7 cc/year; P ≤ 0.05). log-linear models in the Stable group (n = 9) showed significant growth before treatment (53%/year; P = 0.013), and volume reduction (-34%/year; P = 0.037) after 5 months on treatment. After treatment, volume curves were significantly lower than before treatment (after/before treatment ratio 0.5; P < 0.01). Median time-to-best response was 11.2 (IQR: 1.7-33.4) months, and 16.8 (IQR: 2.6-33.5) months in patients on drug for ≥1 year. PFS at 9 months was 75%.
CONCLUSIONS
Ivosidenib was well tolerated and induced a high volumetric response rate. Responders had significant reduction in tumor growth rates and volume reductions observed after a 5-month delay. Thus, ivosidenib appears useful to control tumor growth and delay more toxic therapies in IDH-mutant nonenhancing indolently growing gliomas. See related commentary by Lukas and Horbinski, p. 4709.
Topics: Male; Humans; Middle Aged; Isocitrate Dehydrogenase; Brain Neoplasms; Retrospective Studies; Glioma; Mutation
PubMed: 37382607
DOI: 10.1158/1078-0432.CCR-23-0585 -
Asian Pacific Journal of Cancer... May 2023Prostate-specific membrane antigen (PSMA) was first noticed in prostate cancer cells, thereafter, It has been found in the endothelial cells of neovasculature in a...
BACKGROUND
Prostate-specific membrane antigen (PSMA) was first noticed in prostate cancer cells, thereafter, It has been found in the endothelial cells of neovasculature in a variety of tumors, but not in normal vascular endothelium, This specificity makes PSMA an ideal molecule for vascular targeting in Cancer theranostics (i.e., combined diagnostic and therapeutic).
OBJECTIVES
The objective of this study was to evaluate the immunohistochemical (IHC) expression of PSMA in the neovasculature (identified by CD 31) of high-grade gliomas (HGGs) and to Correlate PSMA IHC expression in HGGs with clinicopathological features, to detect its possible role in tumor angiogenesis, where PSMA can be used as a future diagnostic and therapeutic target.
MATERIALS AND METHODS
This retrospective study included a total of 69 archived, formalin-fixed, paraffin-embedded tissue blocks of HGGs, including 52 cases classified as WHO grade IV (75.4%) and 17 cases as WHO grade III (24.6%). The samples were immunohistochemically analyzed for PSMA expression (in both TMV and parenchymal tumor cells) which was assessed using the composite PSMA immunostaining score. A score (0) was considered negative while scores 1-7 were considered positive (1-4, 5-6, or 7; weak, moderate, or strong respectively).
RESULTS
PSMA is expressed specifically and significantly in endothelial cells of tumor microvessels (TMV) of HGGs, A statistically significant relationship was detected between PSMA IHC expression in both TMV and in parenchymal tumor cells (TC) and various glioma subtypes (P-value < 0.05 and <0.001 respectively). Positive PSMA immunostaining in TMV was detected in all anaplastic ependymoma cases and in near all cases of classic GB and GB with oligodendroglial features more than other subtypes, with P-value specifically for PSMA positivity/negativity in TMV statistically significant (0.022). While for Tumor cells, Positive PSMA immunostaining was detected in all anaplastic ependymoma, most anaplastic astrocytoma and classic GB cases in contrary to other variants, with P-value statistically extremely significant (< 0.001). Comparing PSMA IHC expression in TMV and its expression in TC, it was significantly expressed in TMV of 82.7% versus TC of 51.9% of grade IV cases. Likewise, in GB with oligodendroglial features and gliosarcoma, the majority of cases showed positive staining in their TMV [8/8 (100%), 9/13 (69.2%) respectively], and, the reverse occurs in tumor cells where the majority of cases did NOT show staining in the tumor cells for PSMA (5/8 (62.5%), 11/13 (84.6%) of cases respectively), which was statistically significant (P-value ≤ 0.05) besides the significant difference in the pattern of staining according to composite PSMA scoring (P-value ≤ 0.05).
CONCLUSION
PSMA has a possible role in tumor angiogenesis, therefore it might be considered a potential promising endothelial target for Cancer theranostics with PSMA-based agents, in addition, PSMA was expressed significantly in TC of HGGs, thus, it appears to be involved in biologic behavior, carcinogenesis and tumor progression.
Topics: Humans; Male; Antigens, Surface; Endothelial Cells; Ependymoma; Glioma; Glutamate Carboxypeptidase II; Neovascularization, Pathologic; Prostate; Prostatic Neoplasms; Retrospective Studies
PubMed: 37247303
DOI: 10.31557/APJCP.2023.24.5.1797 -
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