Search Results (25)

Gliomas are incurable, heterogeneous brain tumors, with rare forms often constituting diagnostic and treatment challenges. Molecular diagnostics, mainly implemented through the World Health Organization (WHO) 2021 guidelines, have refined the classification, but highlight difficulties in diagnosing rare gliomas remain. This case series analyzes four patients with rare gliomas treated at the University Hospital, Ulm, between 2002 and 2024. Patients were selected based on unique histopathological features and long-term clinical follow-up. Clinical records, imaging, and histological data were reviewed. Molecular diagnostics followed WHO 2021 guidelines. Quality of life was assessed using standardized tools including the EQ-5D-5L, EQ VAS, the Distress Thermometer, and the Montreal Cognitive Assessment (MoCA). In the first case, a 51-year-old male’s diagnosis evolved from pleomorphic xanthoastrocytoma to a high-grade glioma with pleomorphic and pseudopapillary features, later identified as a neuroepithelial tumor with a PATZ1 fusion over 12 years. Despite multiple recurrences, extensive surgical interventions led to excellent outcomes. The second case involved a young female with long-term survival of astroblastoma, demonstrating significant improvements in both longevity and quality of life through personalized care. The third case involved a patient with oligodendroglioma, later transforming into glioblastoma, emphasizing the importance of continuous diagnostic reevaluation and adaptive treatment strategies, contributing to prolonged survival and quality of life improvements. Remarkably, the patient has achieved over 20 years of survival, including 10 years of being both therapy- and progression-free. The fourth case presents a young woman with neurofibromatosis type 1, initially misdiagnosed with glioblastoma based on histopathological findings. Subsequent molecular diagnostics revealed a subependymal giant cell astrocytoma-like astrocytoma, highlighting the critical role of early advanced diagnostic techniques. These cases underscore the importance of precise molecular diagnostics, individualized treatments, and ongoing diagnostic reevaluation to optimize outcomes. They also address the psychological impact of evolving diagnoses, stressing the need for comprehensive patient support. Even in complex cases, extensive surgical interventions can yield favorable results, reinforcing the value of adaptive, multidisciplinary strategies based on evolving tumor characteristics. Full article

Background/Objectives: Multinodular and vacuolating neuronal tumors (MNVTs) are a type of recently identified benign neuroepithelial tumor with debated malformative or neoplastic origins. This review summarizes their neuroanatomical localization, imaging, histopathology, immunohistochemistry, and diagnostic challenges. Methods: A systematic review of PUBMED/MEDLINE was performed in December 2024. Results: Of 118 screened articles, 39 were eligible, covering 299 patients. MNVTs are often asymptomatic “leave me alone” lesions, discovered incidentally, though nonspecific symptoms (59.9%) and seizures (19.7%) are reported. Immunohistochemistry reveals variable profiles, reflecting complex cellular differentiation. The characteristic “bubble-like” MRI pattern along the subcortical ribbon and superficial white matter is a reliable diagnostic feature. Rare cortical involvement and atypical band-like lesions occur. MRI signal intensity varies. Over a mean follow-up of 36 months, lesions were stable or non-recurrent, with only one case of progression. Conclusion: MVNT imaging mimics other glioneuronal lesions, but reliable diagnostic MRI features include a “bubble-clustered” appearance, lack of cortical involvement, absence of enhancement, and temporal lobe predominance. Hemodynamic and metabolic properties support the diagnosis. Most lesions remain stable, requiring no treatment. Surgical resection is reserved for cases with uncontrolled seizures or atypical locations where the diagnosis is unclear. Full article

Sinonasal teratocarcinosarcoma (TCS) is a rare tumor that displays a variable histology with admixtures of epithelial, mesenchymal, neuroendocrine and germ cell elements. Facing a very poor prognosis, patients with TCS are in need of new options for treatment. Recently identified recurrent mutations in SMARCA4 may serve as target for modern therapies with EZH1/2 and CDK4/6 inhibitors. Here, we present the first in vitro cell line TCS627, established from a previously untreated primary TCS originating in the ethmoid sinus with invasion into the brain. The cultured cells expressed immunohistochemical markers, indicating differentiation of epithelial, neuroepithelial, sarcomatous and teratomatous components. Whole-exome sequencing revealed 99 somatic mutations including SMARCA4, ARID2, TET2, CDKN2A, WNT7A, NOTCH3 and STAG2, all present both in the primary tumor and in the cell line. Focusing on mutated SMARCA4 as the therapeutic target, growth inhibition assays showed a strong response to the CDK4/6 inhibitor palbociclib, but much less to the EZH1/2 inhibitor valemetostat. In conclusion, cell line TCS627 carries both histologic and genetic features characteristic of TCS and is a valuable model for both basic research and preclinical testing of new therapeutic options for treatment of TCS patients. Full article

Introduction: Intraoperative ultrasound (IOUS) may aid the resection of space-occupying brain lesions, though technical limits may hinder its reliability. Methods: IOUS (MyLabTwice^®, Esaote, Italy) with a microconvex probe was utilized in 45 consecutive cases of children with supratentorial space-occupying lesions aiming to localize the lesion (pre-IOUS) and evaluate the extent of resection (EOR, post-IOUS). Technical limits were carefully assessed, and strategies to enhance the reliability of real-time imaging were accordingly proposed. Results: Pre-IOUS allowed us to localize the lesion accurately in all of the cases (16 low-grade gliomas, 12 high-grade gliomas, eight gangliogliomas, seven dysembryoplastic neuroepithelial tumors, five cavernomas, and five other lesions, namely two focal cortical dysplasias, one meningioma, one subependymal giant cell astrocytoma, and one histiocytosis). In 10 deeply located lesions, IOUS with hyperechoic marker, eventually coupled with neuronavigation, was useful to plan the surgical route. In seven cases, the administration of contrast ensured a better definition of the vascular pattern of the tumor. Post-IOUS allowed the evaluation of EOR reliably in small lesions (<2 cm). In large lesions (>2 cm) assessing EOR is hindered by the collapsed surgical cavity, especially when the ventricular system is opened, and by artifacts that may simulate or hide residual tumors. The main strategies to overcome the former limit are inflation of the surgical cavity through pressure irrigation while insonating, and closure of the ventricular opening with Gelfoam before insonating. The strategies to overcome the latter are avoiding the use of hemostatic agents before IOUS and insonating through normal adjacent brain instead of corticotomy. These technical nuances enhanced the reliability of post-IOUS, with a total concordance to postoperative MRI. Indeed, the surgical plan was changed in about 30% of cases, as IOUS showed a residual tumor that was left behind. Conclusion: IOUS ensures reliable real-time imaging in the surgery of space-occupying brain lesions. Limits may be overcome with technical nuances and proper training. Full article

Objective: To determine the predictors and the long-term outcomes of patients with seizures following surgery for dysembryoplastic neuroepithelial tumors (DNTs); Methods: Clinical data were collected from medical records of consecutive patients of the Department of Neurosurgery of Sanbo Brain Hospital of Capital Medical University with a pathological diagnosis of DNT and who underwent surgery from January 2008 to July 2021. All patients were followed up after surgery for at least one year. We estimated the cumulative rate of seizure recurrence-free and generated survival curves. A log-rank (Mantel–Cox) test and a Cox proportional hazard model were performed for univariate and multivariate analysis to analyze influential predictors; Results: 63 patients (33 males and 30 females) were included in this study. At the final follow-up, 49 patients (77.8%) were seizure-free. The cumulative rate of seizure recurrence-free was 82.5% (95% confidence interval (CI) 71.8–91.3%), 79.0% (95% CI 67.8–88.6%) and 76.5% (95% CI 64.8–87.0%) at 2, 5, and 10 years, respectively. The mean time for seizure recurrence-free was 6.892 ± 0.501 years (95% CI 5.91–7.87). Gross total removal of the tumor and a short epilepsy duration were significant predictors of seizure freedom. Younger age of seizure onset, bilateral interictal epileptiform discharges, and MRI type 3 tumors were risk factors for poor prognosis; Conclusions: A favorable long-term seizure outcome was observed for patients with DNT after surgical resection. Predictor analysis could effectively guide the clinical work and evaluate the prognosis of patients with DNT associated with epilepsy. Full article

It has been almost a decade since the multinodular and vacuolating neuronal tumor (MVNT) was first described. In 2021, WHO classified it as a defined entity, and it is considered one of the glioneuronal and neuronal tumors. Due to its similarities with dysembryoplastic neuroepithelial tumors (DNET), some authors consider it a variant of these, ranking in the category of malformations, but genetic alterations favor a neoplastic origin. We present a 29-year-old male with a generalized onset tonic-clonic seizure after a nightclub party. Imaging studies revealed a right temporal multinodular and vacuolating neuronal tumor confirmed by biopsy. It is considered a nonaggressive, “leave me alone” brain lesion, which does not require biopsy because of well-defined MRI characteristics. Surgery is indicated only in symptomatic cases. We consider that this lesion was revealed by his seizure, most probably provoked (with normal video EEG recording) by the consumption of a lot of alcohol, illicit drugs, and sleep loss after a club party. We recommended close monitoring, but our patient preferred the surgery. Our case added more imaging details corroborated with the histopathology features of MVNT. FLAIR images revealed hypointense nodules surrounded by hyperintense peripheral rings and areas of high signal intensity between the nodules, which correspond to the histopathological architecture. To our knowledge, this is the first case of MVNT with diffusion tensor imaging and fiber tractography imaging studies. Full article

Epilepsy surgery in low-grade epilepsy-associated neuroepithelial tumors (LEAT) is usually evaluated in drug-resistant cases, often meaning a time delay from diagnosis to surgery. To identify factors predicting good postoperative seizure control and neuropsychological outcome, the cohort of LEAT patients treated with resective epilepsy surgery at the Epilepsy Center Frankfurt Rhine-Main, Germany between 2015 and 2020 was analyzed. Thirty-five patients (19 males (54.3%) and 16 females, aged 4 to 40 years (M = 18.1), mean follow-up 33 months) were included. Following surgery, 77.1% of patients remained seizure-free (Engel IA/ILAE 1). Hippocampus and amygdala resection was predictive for seizure freedom in temporal lobe epilepsy. In total, 65.7% of all patients showed cognitive deficits during presurgical workup, decreasing to 51.4% after surgery, predominantly due to significantly less impaired memory functions (p = 0.011). Patients with presurgical cognitive deficits showed a tendency toward a longer duration of epilepsy (p = 0.050). Focal to bilateral tonic-clonic seizures (p = 0.019) and young age at onset (p = 0.018) were associated with a higher likelihood of cognitive deficits after surgery. Therefore, we advocate early epilepsy surgery without requiring proof of drug-resistance. This refers especially to lesions associated with the non-eloquent cortex. Full article

Seizures are one of the most common symptoms of brain tumors. The incidence of seizures differs among brain tumor type, grade, location and size, but paediatric-type diffuse low-grade gliomas/glioneuronal tumors are often highly epileptogenic. The extracellular matrix (ECM) is known to play a role in epileptogenesis and tumorigenesis because it is involved in the (re)modelling of neuronal connections and cell-cell signaling. In this review, we discuss the epileptogenicity of brain tumors with a focus on tumor type, location, genetics and the role of the extracellular matrix. In addition to functional problems, epileptogenic tumors can lead to increased morbidity and mortality, stigmatization and life-long care. The health advantages can be major if the epileptogenic properties of brain tumors are better understood. Surgical resection is the most common treatment of epilepsy-associated tumors, but post-surgery seizure-freedom is not always achieved. Therefore, we also discuss potential novel therapies aiming to restore ECM function. Full article

As the most common neuro-epithelial tumors of the central nervous system in adults, gliomas are highly malignant and easy to recurrence, with a dismal prognosis. Imaging studies are indispensable for tracking tumor progression (TP) or treatment-related changes (TRCs). During follow-up, distinguishing TRCs from TP in treated patients with gliomas remains challenging as both share similar clinical symptoms and morphological imaging characteristics (with new and/or increasing enhancing mass lesions) and fulfill criteria for progression. Thus, the early identification of TP and TRCs is of great significance for determining the prognosis and treatment. Histopathological biopsy is currently the gold standard for TP and TRC diagnosis. However, the invasive nature of this technique limits its clinical application. Advanced imaging methods (e.g., diffusion magnetic resonance imaging (MRI), perfusion MRI, magnetic resonance spectroscopy (MRS), positron emission tomography (PET), amide proton transfer (APT) and artificial intelligence (AI)) provide a non-invasive and feasible technical means for identifying of TP and TRCs at an early stage, which have recently become research hotspots. This paper reviews the current research on using the abovementioned advanced imaging methods to identify TP and TRCs of gliomas. First, the review focuses on the pathological changes of the two entities to establish a theoretical basis for imaging identification. Then, it elaborates on the application of different imaging techniques and AI in identifying the two entities. Finally, the current challenges and future prospects of these techniques and methods are discussed. Full article

Pilocytic astrocytoma with a predominant oligodendrocyte-like component can be difficult to distinguish from oligodendroglioma, dysembryoplastic neuroepithelial tumors (DNTs), central neurocytoma, and ependymoma (clear cell phenotype). The utility of GFAP immunostaining in this context is not well discussed. All cases with a diagnosis of pilocytic astrocytoma were retrieved from the pathological archives along with the following information: age, sex, and pathological description. The GFAP immunostaining was scored as score 1 (<25%), score 2 (25–50%), score 3 (50–75%), and score 4 (>75%). The comparison group included oligodendrogliomas, DNTs, ependymomas, and central neurocytomas. All 26 cases (16 males and 10 females) of pilocytic astrocytoma showed strong and diffuse (score 4) GFAP immunostaining in the neoplastic cells of both the solid fibrillary and oligodendrocyte-like components. The staining pattern in the neoplastic round cells in the oligodendrocyte-like areas was perinuclear cytoplasmic with no processes. In the comparison group, GFAP immunostaining was mostly restricted to the reactive astrocytes in the background. Focal areas of the neoplastic cells showed scores of 1–3 in the neoplastic cells, but the staining pattern was different from those in pilocytic astrocytoma. In the setting of tumors with predominant oligodendrocyte-like areas, the GFAP immunostaining score and pattern help distinguish pilocytic astrocytoma from its mimickers. Full article

Telomeres are DNA–protein complexes that protect eukaryotic chromosome ends from being erroneously repaired by the DNA damage repair system, and the length of telomeres indicates the replicative potential of the cell. Telomeres shorten during each division of the cell, resulting in telomeric damage and replicative senescence. Tumor cells tend to ensure cell proliferation potential and genomic stability by activating telomere maintenance mechanisms (TMMs) for telomere lengthening. The alternative lengthening of telomeres (ALT) pathway is the most frequently activated TMM in tumors of mesenchymal and neuroepithelial origin, and ALT also frequently occurs during experimental cellular immortalization of mesenchymal cells. ALT is a process that relies on homologous recombination (HR) to elongate telomeres. However, some processes in the ALT mechanism remain poorly understood. Here, we review the most recent understanding of ALT mechanisms and processes, which may help us to better understand how the ALT pathway is activated in cancer cells and determine the potential therapeutic targets in ALT pathway-stabilized tumors. Full article

Background: Processing whole-slide images (WSI) to train neural networks can be intricate and labor intensive. We developed an open-source library dealing with recurrent tasks in the processing of WSI and helping with the training and evaluation of neuronal networks for classification tasks. Methods: Two histopathology use-cases were selected and only hematoxylin and eosin (H&E) stained slides were used. The first use case was a two-class classification problem. We trained a convolutional neuronal network (CNN) to distinguish between dysembryoplastic neuroepithelial tumor (DNET) and ganglioglioma (GG), two neuropathological low-grade epilepsy-associated tumor entities. Within the second use case, we included four clinicopathological disease conditions in a multilabel approach. Here we trained a CNN to predict the hormone expression profile of pituitary adenomas. In the same approach, we also predicted clinically silent corticotroph adenoma. Results: Our DNET-GG classifier achieved an AUC of 1.00 for the ROC curve. For the second use case, the best performing CNN achieved an area under the curve (AUC) of 0.97 for the receiver operating characteristic (ROC) for corticotroph adenoma, 0.86 for silent corticotroph adenoma, and 0.98 for gonadotroph adenoma. All scores were calculated with the help of our library on predictions on a case basis. Conclusions: Our comprehensive and fastai-compatible library is helpful to standardize the workflow and minimize the burden of training a CNN. Indeed, our trained CNNs extracted neuropathologically relevant information from the WSI. This approach will supplement the clinicopathological diagnosis of brain tumors, which is currently based on cost-intensive microscopic examination and variable panels of immunohistochemical stainings. Full article

Background. Malformations of cortical development (MCD) include a wide range of congenital disorders mostly causing severe cognitive dysfunction and epilepsy. Objective: to report on clinical features including cognitive involvement, epileptic seizures with response to antiseizure medications, comorbidities in young patients affected by MCD and followed in a single tertiary hospital. Patients and methods: A retrospective review of the medical records and magnetic resonance images (MRI) of 19 young patients with an age ranging between eight days and fifteen years affected by MCD and admitted to Pediatrics Department University of Catania, Italy from October 2009 and October 2020 were selected. Patients were distinguished in three groups following the Barcovich et al. 2012 classification for MCD: 4 (21%) in Group I; 8 (42%) in Group II; and, and 7 (37%) in Group III. Clinical features and MRI of the patients including cognitive involvement, epilepsy type and response to drugs treatment were analyzed. Results: In Group I, two patients showed cortical dysplasia and two dysembryoplastic neuroepithelial tumors plus focal cortical dysplasia; developmental delay/intellectual disability (DD/ID) was severe in one, moderate in one and absent in two; the type of seizures was in all the cases focal to bilateral tonic-clonic (FBTCs), and drug resistant was found in one case. In Group II, three patients showed neuronal hetero-topias and five had pachygyria-lissencephaly: DD/ID was severe in four, moderate in two, and absent in two; the type of seizure was focal (FS) in five, focal to bilateral tonic-clonic (FBTCs) in two, infantile spasms (IS) in one, and drug resistant was found in three. In Group III, six showed polymicrogyria and one schizencephaly: DD/ID was found severe in five, moderate in two, and the type of seizure was focal (FS) in five, FBTCS in two, and drug resistance was found in three. Full article

Olfactory neuroblastoma (ONB) is a rare neuroepithelial-derived malignancy that usually presents in the nasal cavity. The rarity of ONB has led to conflicting reports regarding associations of patient age and ONB survival and outcome. Moreover, long-term outcomes of chemotherapy and other treatment modalities are speculated. Here, we aimed to compare survival outcomes across age groups through time and determine associations between treatment modality and survival. In this retrospective population-based study, we analyzed the SEER 2000–2016 Database for patients with ONB tumors. Using Kaplan–Meier survival analysis, a significant effect of age and cancer-specific survival (CSS) was observed; geriatric ONB patients had the lowest CSS overall. Generalized linear models and survival analyses demonstrated that CSS of the pediatric patient population was similar to the geriatric group through 100 months but plateaued thereafter and was the highest of all age groups. Radiation and surgery were associated with increased CSS, while chemotherapy was associated with decreased CSS. GLM results showed that tumor grade, stage and lymph node involvement had no CSS associations with age or treatment modality. Our results provide insight for future investigations of long-term outcomes associated with ONB patient age and treatment modality, and we conclude that survival statistics of ONB patients should be analyzed in terms of trends through time rather than fixed in time. Full article

Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. In this study, we introduced either wildtype BCOR or BCOR-ITD into human and murine neural stem cells and analyzed them with quantitative RT-PCR and RNA-sequencing, as well as growth, clonogenicity, and invasion assays. In human cells, BCOR-ITD promoted derepression of PRC2-target genes compared to wildtype BCOR. A similar effect was found in clinical specimens from previous studies. However, no growth advantage was seen in the human neural stem cells expressing BCOR-ITD, and long-term models could not be established. In the murine cells, both wildtype BCOR and BCOR-ITD overexpression affected cellular differentiation and histone methylation, but only BCOR-ITD increased cellular growth, invasion, and migration. BCOR-ITD overexpression drives transcriptional changes, possibly due to altered PRC function, and contributes to the oncogenic transformation of neural precursors. Full article