Deep Residual Learning-Based Classification with Identification of Incorrect Predictions and Quantification of Cellularity and Nuclear Morphological Features in Digital Pathological Images of Common Astrocytic Tumors.

Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors.

Pediatric-type diffuse low-grade gliomas.

The World Health Organization's 5th edition classification of Central Nervous System (CNS) tumors differentiates diffuse gliomas into adult and pediatric variants. Pediatric-type diffuse low-grade gliomas (pDLGGs) are distinct from adult gliomas in their molecular characteristics, biological behavior, clinical progression, and prognosis. Various molecular alterations identified in pDLGGs are crucial for treatment. There are four distinct entities of pDLGGs. All four of these tumor subtypes exhibit diffuse growth and share overlapping histopathological and imaging characteristics. Molecular analysis is essential for differentiating these lesions.

Bilateral tinnitus associated with a diffuse astrocytoma of Heschl's gyrus: a case report and review of literature.

Auditory processing is initiated within the primary auditory cortex, concealed within the sylvian fissure bilaterally on a collection of gyri described as Heschl's Gyrus (HG). Glial neoplasms localized to or involving HG are rare. The main symptoms of these tumours are complex partial seizures characterized by auditory features. Here, we describe an unusual case of bilateral tinnitus and hemi-paraesthesia associated with a HG diffuse astrocytoma. Bilateral tinnitus secondary to intrinsic brain tumours is atypical. Bilateral tinnitus is frequently observed in patients with noise-induced hearing loss, presbycusis, ototoxic medication, and metabolic and psychiatric disease. In the case we present, the synchronous sensory and auditory symptoms are likely due to seizure activity affecting the primary auditory and somatosensory cortex. In a patient presenting with chronic, bilateral tinnitus with no known underlying otologic disease which is associated with hemi-body paraesthesia, we would advocate for consideration of brain imaging to exclude pathology in HG.

Neurophysiotherapy in Grade II Diffuse Astrocytoma: A Case Report.

Diffuse astrocytoma is a slow, progressive, and invasive tumor that develops from astrocytes and there is no discernible boundary between tumor and brain cells. We present a case of a 48-year-old woman with diffuse astrocytoma who experienced sudden left-sided weakness, multiple convulsive episodes, and vomiting. The patient underwent surgery for a left occipital mini craniotomy with complete tumor removal through a titanium burr hole. Postoperatively, the patient complained of bilateral upper and lower extremities weakness, and decreased muscular tone was found; hence, she was referred to undergo neurophysiotherapy. A four-week rehabilitative protocol was started. Physiotherapy is critical in these patients for ensuring early and rapid recovery and treating the condition's clinical manifestations. The outcome measures employed were the tone grading scale, the Brunnstrom recovery stage, and the Functional Independence Measure (FIM). This case study concludes that physiotherapy rehabilitation for an operated case of grade 2 diffuse astrocytoma led to improved lower limb strength, normal tone, and improved functional independence, which helped the patient achieve better functional activities and a greater quality of life.

Benign Glioma.

Benign glioma broadly refers to a heterogeneous group of slow-growing glial tumors with low proliferative rates and a more indolent clinical course. These tumors may also be described as "low-grade" glioma (LGG) and are classified as WHO grade I or II lesions according to the Classification of Tumors of the Central Nervous System (CNS) (Louis et al. in Acta Neuropathol 114:97-109, 2007). Advances in molecular genetics have improved understanding of glioma tumorigenesis, leading to the identification of common mutation profiles with significant treatment and prognostic implications. The most recent WHO 2016 classification system has introduced several notable changes in the way that gliomas are diagnosed, with a new emphasis on molecular features as key factors in differentiation (Wesseling and Capper in Neuropathol Appl Neurobiol 44:139-150, 2018). Benign gliomas have a predilection for younger patients and are among the most frequently diagnosed tumors in children and young adults (Ostrom et al. in Neuro Oncol 22:iv1-iv96, 2020). These tumors can be separated into two clinically distinct subgroups. The first group is of focal, well-circumscribed lesions that notably are not associated with an increased risk of malignant transformation. Primarily diagnosed in pediatric patients, these WHO grade I tumors may be cured with surgical resection alone (Sturm et al. in J Clin Oncol 35:2370-2377, 2017). Recurrence rates are low, and the prognosis for these patients is excellent (Ostrom et al. in Neuro Oncol 22:iv1-iv96, 2020). Diffuse gliomas are WHO grade II lesions with a more infiltrative pattern of growth and high propensity for recurrence. These tumors are primarily diagnosed in young adult patients, and classically present with seizures (Pallud et al. Brain 137:449-462, 2014). The term "benign" is a misnomer in many cases, as the natural history of these tumors is with malignant transformation and recurrence as grade III or grade IV tumors (Jooma et al. in J Neurosurg 14:356-363, 2019). For all LGG, surgery with maximal safe resection is the treatment of choice for both primary and recurrent tumors. The goal of surgery should be for gross total resection (GTR), as complete tumor removal is associated with higher rates of tumor control and seizure freedom. Chemotherapy and radiation therapy (RT), while not typically a component of first-line treatment in most cases, may be employed as adjunctive therapy in high-risk or recurrent tumors and in some select cases. The prognosis of benign gliomas varies widely; non-infiltrative tumor subtypes generally have an excellent prognosis, while diffusely infiltrative tumors, although slow-growing, are eventually fatal (Sturm et al. in J Clin Oncol 35:2370-2377, 2017). This chapter reviews the shared and unique individual features of the benign glioma including diffuse glioma, pilocytic astrocytoma and pilomyxoid astrocytoma (PMA), subependymal giant cell astrocytoma (SEGA), pleomorphic xanthoastrocytoma (PXA), subependymoma (SE), angiocentric glioma (AG), and chordoid glioma (CG). Also discussed is ganglioglioma (GG), a mixed neuronal-glial tumor that represents a notable diagnosis in the differential for other LGG (Wesseling and Capper 2018). Ependymomas of the brain and spinal cord, including major histologic subtypes, are discussed in other chapters.

Diagnostic algorithm for pathological evaluation of gliomas in a resource-constrained setting.

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.

Awake Craniotomy for Resection of Diffuse Astrocytoma During Pregnancy: A Case Report.

Brain tumors rarely present during pregnancy; however, a life-threatening interaction may develop between maternal and disease factors. Moreover, awake surgery has been an infrequent treatment option during this life stage. We contribute to this knowledge gap by presenting the case of a 33-year-old woman who developed tonic-clonic seizures during the 18th week of pregnancy due to a neoplastic lesion near the left motor area. A multidisciplinary team performed an awake craniotomy for tumor resection and the histopathological examination revealed a diffuse astrocytoma. On the follow-up, radiotherapy was administered and the patient delivered a healthy newborn at week 37.

IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma: a case report.

Primary glioblastoma develops de novo without clinical or histological evidence of a low-grade precursor lesion, whereas secondary glioblastoma develops from a low-grade glioma. The present report describes an extraordinary case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma. A 31-year-old female had a surgical history of IDH-mutant diffuse astrocytoma on the left frontal lobe six years before. Magnetic resonance imaging revealed new infiltrative lesions in the left frontal lobe adjacent to the previous lesion. The patient underwent tumourectomy, and the new infiltrative lesion was diagnosed as glioblastoma. Interestingly, the IDH-1 (p.Arg132His) mutation was found in diffuse astrocytoma but not in glioblastoma based on next generation sequencing. ATRX (p.Gln1670Ter) and TP53 (p.His193Arg) mutations were found in both lesions. Additionally, the PTEN (p.His296Pro) mutation was identified only in glioblastoma. A well-accepted hypothesis is that the IDH mutation initiates in glial progenitor cells and causes secondary glioblastoma harboring the IDH mutation to develop from low grade glioma with IDH mutation. However, this case showed that the other genetic mutations can be initiated before the IDH mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma.

Paediatric-type diffuse low-grade gliomas: a clinically and biologically distinct group of tumours with a favourable outcome.

The WHO 2021 classification of central nervous system cancers distinguishes diffuse gliomas that arise in adults (referred to as the "adult type") and those that arise in children (defined as "paediatric") based on clinical and molecular characteristics."). However, paediatric-type gliomas may occasionally be present in younger adults and occasionally adult-type gliomas may occur in children. Diffuse low-grade paediatric glioma includes diffuse astrocytoma altered by MYB or MYBL1, low-grade polymorphic juvenile neuroepithelial tumour, angiocentric glioma, and diffuse low-grade glioma with an altered MAPK pathway. Here, we examine these newly recognised entities according to WHO diagnostic criteria and propose an integrated diagnostic approach that can be used to separate these clinically and biologically distinct tumor groups.

Malignant transformation in low-grade astrocytoma for long-term monitoring.

Background: Malignant transformation (MT) of low-grade astrocytoma (LGA) produces a poor prognosis in benign tumors. Currently, variables linked with MT of LGA have proven equivocal. The present study aims to evaluate the risk variables, indicating that LGA gradually differentiates to malignant astrocytoma. Methods: Retrospective cohort analysis of LGA patients was performed. Both univariate and multivariate studies were used to discover variables connected to MT using the Cox regression method. As a result, the cumulative incidence of MT for each covariate survival curve was built after the final model. Results: In the current study, 115 individuals with LGA were included in the analysis, and MT was found in 16.5% of cases. In the case of MT, 68.4% of patients progressed to glioblastoma, whereas 31.6% progressed to anaplastic astrocytoma. Significant factors included supratentorial tumor (hazard ratio (HR) 3.41, 95% CI 1.18-12.10), midline shift > 5 mm (HR 7.15, 95% CI 2.28-34.33), and non-total resection as follows: subtotal resection (HR 5.09, 95% CI 0.07-24.02), partial resection (HR 1.61, 95% CI 1.09-24.11), and biopsy (HR 2.80, 95% CI 1.18-32.52). Conclusion: In individuals with LGA, MT dramatically altered the disease's natural history to a poor prognosis. The present study's analysis of the clinical features of patients indicated supratentorial LGA, a midline shift greater than 5 mm, and the degree of resection as risk factors for MT. The more extensive the resection, the greater the reduction in tumor load and MT. In addition, more molecular study is necessary to elucidate the pathophysiology of MT.

An MRI-based joint model of radiomics and spatial distribution differentiates autoimmune encephalitis from low-grade diffuse astrocytoma.

Background: The differential diagnosis between autoimmune encephalitis and low-grade diffuse astrocytoma remains challenging. We aim to develop a quantitative model integrating radiomics and spatial distribution features derived from MRI for discriminating these two conditions. Methods: In our study, we included 188 patients with confirmed autoimmune encephalitis (n = 81) and WHO grade II diffuse astrocytoma (n = 107). Patients with autoimmune encephalitis (AE, n = 59) and WHO grade II diffuse astrocytoma (AS, n = 79) were divided into training and test sets, using stratified sampling according to MRI scanners. We further included an independent validation set (22 patients with AE and 28 patients with AS). Hyperintensity fluid-attenuated inversion recovery (FLAIR) lesions were segmented for each subject. Ten radiomics and eight spatial distribution features were selected via the least absolute shrinkage and selection operator (LASSO), and joint models were constructed by logistic regression for disease classification. Model performance was measured in the test set using the area under the receiver operating characteristic (ROC) curve (AUC). The discrimination performance of the joint model was compared with neuroradiologists. Results: The joint model achieved better performance (AUC 0.957/0.908, accuracy 0.914/0.840 for test and independent validation sets, respectively) than the radiomics and spatial distribution models. The joint model achieved lower performance than a senior neuroradiologist (AUC 0.917/0.875) but higher performance than a junior neuroradiologist (AUC 0.692/0.745) in the test and independent validation sets. Conclusion: The joint model of radiomics and spatial distribution from a single FLAIR could effectively classify AE and AS, providing clinical decision support for the differential diagnosis between the two conditions.

Resilience in Lower Grade Glioma Patients.

Current data show that resilience is an important factor in cancer patients' well-being. We aim to explore the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. We performed a cross-sectional assessment of adult patients with LGG who were enrolled in the LoG-Glio registry. By phone interview, we administered the following measures: Resilience Scale (RS-13), distress thermometer, Montreal Cognitive Assessment Test for visually impaired patients (MoCA-Blind), internalized stigmatization by brain tumor (ISBI), Eastern Cooperative Oncological Group performance status (ECOG), patients' perspective questionnaire (PPQ) and typical clinical parameters. We calculated correlations and multivariate regression models. Of 74 patients who were assessed, 38% of those showed a low level of resilience. Our results revealed significant correlations of resilience with distress (p < 0.001, −0.49), MOCA (p = 0.003, 0.342), ECOG (p < 0.001, −0.602), stigmatization (p < 0.001, −0.558), pain (p < 0.001, −0.524), and occupation (p = 0.007, 0.329). In multivariate analyses, resilience was negatively associated with elevated ECOG (p = 0.020, ß = −0.383) and stigmatization levels (p = 0.008, ß = −0.350). Occupation showed a tendency towards a significant association with resilience (p = 0.088, ß = −0.254). Overall, low resilience affected more than one third of our cohort. Low functional status is a specific risk factor for low resilience. The relevant influence of stigmatization on resilience is a novel finding for patients suffering from a glioma and should be routinely identified and targeted in clinical routine.

True anaplastic oligoastrocytoma with dual genotype: illustrative case.

BACKGROUND: The revised fourth edition of the World Health Organization classification of central nervous system tumors was published in 2016. Based on this classification, one of the infiltrating glioma entities named "oligoastrocytoma/anaplastic oligoastrocytoma" is discouraged. It is proposed that these mixed gliomas should be classified as diffuse astrocytoma/anaplastic astrocytoma or oligodendroglioma/anaplastic oligodendroglioma when analyzing their genetic alteration. OBSERVATIONS: A 78-year-old female underwent brain computed tomography (CT) because of a traffic accident. Cranial CT revealed a brain tumor in the left temporoparietal lobe; therefore, she was hospitalized. She underwent awake craniotomy. After the operation, she was treated with only local radiotherapy; the authors could not prescribe temozolomide, because she had had levetiracetam-induced pancytopenia. The remaining tumor neuroradiologically disappeared, and she was alive 40 months after the operation without tumor recurrence. LESSONS: Histopathologically, this tumor was diagnosed as an anaplastic oligoastrocytoma with a distinct dual phenotype of astrocytoma and oligodendroglioma components. Genetically, these two components revealed astrocytoma and oligodendroglioma genotypes, respectively. Therefore, the authors considered the integrated diagnosis of the temporal tumor as a true anaplastic oligoastrocytoma with a dual genotype. Interestingly, this case also included an area composed of spindle to oval neoplastic cells that revealed intermediate genetic alterations between astrocytomas and oligodendrogliomas.

5-Aminolevulinic Acid-A Biomarker for Worse Prognosis in IDH-Wildtype II Tumors? Evolution of a Fluorescence-Positive Diffuse Astrocytoma: A Case Report.

Introduction In 2017, the U.S. Food and Drug Administration (FDA) approved 5-aminolevulinic acid (5-ALA) as an intraoperative optical imaging agent in patients with suspected high-grade gliomas (HGGs). However, the application of 5-ALA for low-grade gliomas is still less accepted. Astrocytoma, isocitrate dehydrogenase (IDH) mutant tumors are diffuse infiltrating astrocytic tumors where there is no identifiable border between the tumor and normal brain tissue, even though the borders may appear relatively well-marginated on imaging. Generally, it is considered that 5-ALA cannot pass through a normal blood-brain barrier (BBB). Thus, 5-ALA fluorescence may mean disruption of BBB in grade II glioma. Case Report A 74-year-old male patient was diagnosed with a right parietal lesion suggestive of a low-grade brain tumor in a surgical resection using 5-ALA, which led to the detection of tiny fluorescence spots during the surgery. The frozen section was consistent with diffuse astrocytoma, IDH-wildtype (World Health Organization [WHO] grade II). The patient's postoperative magnetic resonance imaging (MRI) showed complete resection. Eight months after surgery, he began experiencing symptoms again and was admitted with a brain MRI finding consistent with recurrent infiltrating astrocytomas. This required reoperation of the brain tumor resection with 5-ALA. Unlike the first surgery, they observed a high fluorescence intensity; the pathological finding was glioblastoma, IDH-wildtype (WHO grade IV). Postsurgical brain MRI showed total resection of the tumor. The patient was discharged 4 weeks after surgery and continued with specialized clinical follow-up. Conclusion The use of 5-ALA continues to be a great contributor to the improvement in complete resection of primary brain tumors, especially HGG. Besides, fluorescence is increasingly approaching its use as a prognostic tool for aggressive clinical course, regardless of the initial grade of the tumor. This case report is an effort to expand knowledge for potentially using 5-ALA to help prognosticate brain tumors. Nevertheless, more clinical prospective studies must be conducted.

Risk Factors Associated with Malignant Transformation of Astrocytoma: Competing Risk Regression Analysis.

Background Malignant transformation (MT) of low-grade astrocytoma (LGA) triggers a poor prognosis in benign tumors. Currently, factors associated with MT of LGA have been inconclusive. The present study aims to explore the risk factors predicting LGA progressively differentiated to malignant astrocytoma. Methods The study design was a retrospective cohort study of medical record reviews of patients with LGA. Using the Fire and Gray method, the competing risk regression analysis was performed to identify factors associated with MT, using both univariate and multivariable analyses. Hence, the survival curves of the cumulative incidence of MT of each covariate were constructed following the final model. Results Ninety patients with LGA were included in the analysis, and MT was observed in 14.4% of cases in the present study. For MT, 53.8% of patients with MT transformed to glioblastoma, while 46.2% differentiated to anaplastic astrocytoma. Factors associated with MT included supratentorial tumor (subdistribution hazard ratio [SHR] 4.54, 95% confidence interval [CI] 1.08-19.10), midline shift > 1 cm (SHR 8.25, 95% CI 2.18-31.21), and nontotal resection as follows: subtotal resection (SHR 5.35, 95% CI 1.07-26.82), partial resection (SHR 10.90, 95% CI 3.13-37.90), and biopsy (SHR 11.10, 95% CI 2.88-42.52). Conclusion MT in patients with LGA significantly changed the natural history of the disease to an unfavorable prognosis. Analysis of patients' clinical characteristics from the present study identified supratentorial LGA, a midline shift more than 1 cm, and extent of resection as risk factors associated with MT. The more extent of resection would significantly help to decrease tumor burden and MT. In addition, future molecular research efforts are warranted to explain the pathogenesis of MT.

The early infiltrative phase of GBM hypothesis: are molecular glioblastomas histological glioblastomas in the making? A preliminary multicenter study.

PURPOSE: The presence of necrosis or microvascular proliferation was previously the hallmark for glioblastoma (GBM) diagnosis. The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/-10 copy changes. We hypothesize that these tumors are early histological GBM and will eventually develop the classic histological features. METHODS: Medical records from 65 consecutive patients diagnosed with molGBM at three tertiary-care centers from our institution were retrospectively reviewed from November 2017-October 2021. Only patients who underwent reoperation for tumor recurrence and whose tissue at initial diagnosis and recurrence was available were included in this study. The detailed clinical, histopathological, and radiographic scenarios are presented. RESULTS: Five patients were included in our final cohort. Three (60%) patients underwent reoperation for recurrence in the primary site and 2 (40%) underwent reoperation for distal recurrence. Microvascular proliferation and pseudopalisading necrosis were absent at initial diagnosis but present at recurrence in 4 (80%) patients. Radiographically, all tumors showed contrast enhancement, however none of them showed the classic radiographic features of GBM at initial diagnosis. CONCLUSIONS: In this manuscript we present preliminary data for a hypothesis that molGBMs are early histological GBMs diagnosed early in their natural history of disease and will eventually develop necrosis and microvascular proliferation. Further correlative studies are needed in support of this hypothesis.

The survival outcomes of molecular glioblastoma IDH-wildtype: a multicenter study.

PURPOSE: Histological diagnosis of glioblastoma (GBM) was determined by the presence of necrosis or microvascular proliferation (histGBM). The 2021 WHO classification now considers IDH-wildtype diffuse astrocytic tumors without the histological features of glioblastoma (that would have otherwise been classified as grade 2 or 3) as molecular GBM (molGBM, WHO grade 4) if they harbor any of the following molecular abnormalities: TERT promoter mutation, EGFR amplification, or chromosomal + 7/- 10 copy changes. The objective of this study was to explore and compare the survival outcomes between histGBM and molGBM. METHODS: Medical records for patients diagnosed with GBM at the three tertiary care academic centers of our institution from November 2017 to October 2021. Only patients who underwent adjuvant chemoradiation were included. Patients without molecular feature testing or with an IDH mutation were excluded. Univariable and multivariable analyses were performed to evaluate progression-free (PFS) and overall- survival (OS). RESULTS: 708 consecutive patients were included; 643 with histGBM and 65 with molGBM. Median PFS was 8 months (histGBM) and 13 months (molGBM) (p = 0.0237) and median OS was 21 months (histGBM) versus 26 months (molGBM) (p = 0.435). Multivariable analysis on the molGBM sub-group showed a worse PFS if there was contrast enhancement on MRI (HR 6.224 [CI 95% 2.187-17.714], p < 0.001) and a superior PFS on patients with MGMT methylation (HR 0.026 [CI 95% 0.065-0.655], p = 0.007). CONCLUSIONS: molGBM has a similar OS but significantly longer PFS when compared to histGBM. The presence of contrast enhancement and MGMT methylation seem to affect the clinical behavior of this subset of tumors.

Malignant Progression of Diffuse Low-grade Gliomas: A Systematic Review and Meta-analysis on Incidence and Related Factors.

Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent in literature. According to the PRISMA guidelines, we systematically reviewed articles from 2009, meta-analyzed the incidence of malignant progression, and clarified factors related to the transformation. Forty-one articles were included in this study (n = 7,122; n, number of patients). We identified two definitions of malignant progression: histologically proven (Htrans) and clinically defined (Ctrans). The malignant progression rate curves of Htrans and Ctrans were almost in parallel when constructed from the results of meta-regression by the mean follow-up time. The true transformation rate was supposed to lie between the two curves, approximately 40% at the 10-year mean follow-up. Risk of malignant progression was evaluated using hazard ratio (HR). Pooled HRs were significantly higher in tumors with a larger pre- and postoperative tumor volume, lower degree of resection, and notable preoperative contrast enhancement on magnetic resonance imaging than in others. Oligodendroglial histology and IDH mutation (IDHm) with 1p/19q codeletion (Codel) also significantly reduced the HRs. Using Kaplan-Meier curves from eight studies with molecular data, we extracted data and calculated the 10-year malignant progression-free survival (10yMPFS). The 10yMPFS in patients with IDHm without Codel was 30.4% (95% confidence interval [95% CI]: 22.2-39.0) in Htrans and 38.3% (95% CI: 32.3-44.3) in Ctrans, and that with IDHm with Codel was 71.7% (95% CI: 61.7-79.5) in Htrans and 62.5% (95% CI: 55.9-68.5) in Ctrans. The effect of adjuvant radiotherapy or chemotherapy could not be determined.

Early atypical malignant transformation of diffuse low-grade astrocytoma: The importance of genotyping / Transformación maligna atípica temprana de astrocitoma difuso de bajo grado: la importancia de genotipificar

Diffuse astrocytoma (WHO grade II) has classically been considered a slow growing tumour, typically affecting young adults, with tendency for late malignant conversion. We describe a case of early atypical malignant transformation of diffuse astrocytoma seventeen months after complete surgical removal, as an intraventricular high-grade glioma (HGG). Retrospective laboratory findings for the presence of IDH 1/2 (isocitrate dehydrogenase) mutations were negative. There is growing evidence that IDH-wildtype (wt) astrocytomas behave more aggressively, therefore identifying IDH-mutation status should be mandatory in order to determine disease prognosis and guide treatment course (AU)

Clásicamente, el astrocitoma difuso (OMS II) se clasificaba como neoplasia de crecimiento lento, afectando a adultos jóvenes y con tendencia para conversión maligna tardía. Reportamos un caso de transformación maligna temprana de astrocitoma difuso de grado bajo 17 meses después de remoción tumoral completa, como glioma intraventricular de grado alto. Un análisis retrospectivo para la presencia de la mutación IDH 1/2 fue negativo. La creciente evidencia demuestra que los astrocitomas IDH-wildtype se comportan de forma más agresiva, así que identificar la mutación IDH debería ser mandatorio para determinar el pronóstico y redireccionar el tratamiento de los astrocitomas (AU)

Low grade gliomas.

Low grade gliomas concern grade I and grade II tumors. The only grade one tumor is the pilocytic astrocytoma. This is a well-defined tumor with characteristic histology, often accompanied by a cyst. GKNS has been used in surgically inaccessible tumors since 1994. More recently it has been demonstrated that the tumors are more treatment resistant in adults than in children. Grade II tumors include oligodendrogliomas and grade II diffuse astrocytomas. The standard treatment for oligodendrogliomas us total removal followed by fractionated radiotherapy. GKNS has been shown to be of benefit in smaller tumors which have not responded to other treatment. It may also have a role as an ancillary treatment in smaller Grade II astrocytomas.