Revisiting prognostic factors of gliomatosis cerebri in adult-type diffuse gliomas.

PURPOSE: There is lack of comprehensive analysis evaluating the impact of clinical, molecular, imaging, and surgical data on survival of patients with gliomatosis cerebri (GC). This study aimed to investigate prognostic factors of GC in adult-type diffuse glioma patients. METHODS: Retrospective chart and imaging review was performed in 99 GC patients from adult-type diffuse glioma (among 1,211 patients; 6 oligodendroglioma, 16 IDH-mutant astrocytoma, and 77 IDH-wildtype glioblastoma) from a single institution between 2005 and 2021. Predictors of overall survival (OS) of entire patients and IDH-wildtype glioblastoma patients were determined. RESULTS: The median OS was 16.7 months (95% confidence interval [CI] 14.2-22.2) in entire patients and 14.3 months (95% CI 12.2-61.9) in IDH-wildtype glioblastoma patients. In entire patients, KPS (hazard ratio [HR] = 0.98, P = 0.004), no 1p/19q codeletion (HR = 10.75, P = 0.019), MGMTp methylation (HR = 0.54, P = 0.028), and hemorrhage (HR = 3.45, P = 0.001) were independent prognostic factors on multivariable analysis. In IDH-wildtype glioblastoma patients, KPS (HR = 2.24, P = 0.075) was the only independent prognostic factor on multivariable analysis. In subgroup of IDH-wildtype glioblastoma with CE tumors, total resection of CE tumor did not remain as a significant prognostic factor (HR = 1.13, P = 0.685). CONCLUSIONS: The prognosis of GC patients is determined by its underlying molecular type and patient performance status. Compared with diffuse glioma without GC, aggressive surgery of CE tumor in GC patients does not improve survival.

Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

BACKGROUND: The term Gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features have not been established yet. METHODS: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization. RESULTS: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-years survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n=49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wildtype (n=31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n=19), pedHGG_A/B (n=6), and pedHGG_MYCN (n=5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wildtype subgroup, recurrent alterations in EGFR (n=10) and BCOR (n=9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wildtype subgroup TP53 alterations had a significant negative effect on OS. CONCLUSION: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).

Gliomatosis cerebri (GC) growth pattern: A single-center analysis of clinical, histological, and molecular characteristics of GC and non-GC glioblastoma.

Background: The biological understanding of glioblastoma (GB) with gliomatosis cerebri (GC) pattern is poor due to the absence of GC-specific studies. Here, we aimed to identify molecular or clinical parameters that drive GC growth. Methods: From our methylome database of IDH (isocitrate dehydrogenase)-wildtype GB, we identified 158 non-GC and 65 GC cases. GC cases were subdivided into diffuse-infiltrative (subtype 1), multifocal (subtype 2), or tumors with 1 solid mass (subtype 3). We compared clinical, histological, and molecular parameters and conducted a reference-free tumor deconvolution of DNA methylation data based on latent methylation components (LMC). Results: GC subtype 1 less frequently showed contrast-enhancing tumors, and more frequently lacked morphological GB criteria despite displaying GB DNA methylation profile. However, the tumor deconvolution did not deliver a specific LMC cluster for either of the GC subtypes. Employing the reference-based analysis MethylCIBERSORT, we did not identify significant differences in tumor cell composition. The majority of both GC and non-GC patients received radiochemotherapy as first-line treatment, but there was a major imbalance for resection. The entire GC cohort had significantly shorter overall survival (OS) and time to treatment failure (TTF) than the non-GC cohort. However, when filtering for cases in which only stereotactic biopsy was performed, the comparison of OS and TTF lost statistical significance. Conclusions: Our study offers clinically relevant information by demonstrating a similar outcome for GB with GC growth pattern in the surgically matched analysis. The limited number of cases in the GC subgroups encourages the validation of our DNA methylation analysis in larger cohorts.

[Diffuse infiltrating primary cerebellar glioma involving the brainstem: a case report].

An 85-year-old woman was admitted to our hospital with unsteady gait, dizziness, nausea, and vomiting. MRI revealed characteristic abnormal signals in the bilateral cerebellar hemispheres. A brain biopsy was performed which confirmed a definitive histological diagnosis of diffuse glioma. Follow-up MRI showed diffuse abnormal signals that extended from the cerebellum to the brainstem through the cerebellar peduncle without mass formation. Her general condition gradually deteriorated even with the best supportive care, and she died 195 days after admission. Gliomatosis cerebri is characterized by a diffuse infiltrating growth pattern without mass formation in the brain. This case showed a similar proliferation mode from the cerebellum to the brain stem without mass formation. This case was diagnosed based on MRI and pathological findings. Only five similar cases have been previously reported, and compared to these reports, the patient in the present case was the oldest with the poorest prognosis. The histopathological features may influence the appropriate treatment and the prognosis. This disorder is a very rare condition; thus, when we encountered this patient showing cerebellar ataxia with diffuse abnormal MRI signals without mass formation in the cerebellum and brainstem, a brain biopsy was necessary to establish the definitive diagnosis.

Gliomatosis cerebri with blindness: A case report with literature review.

Cerebral gliomatosis (GC) is a rare diffuse infiltrative growth pattern of glioma with nonspecific clinical manifestations like visual impairment that may involve bilateral temporal lobes. Herpes simplex encephalitis (HSE) and limbic encephalitis (LE) can also lead to temporal lobe involvement. Differentiating these entities is necessary for patients with misleading presentations and imaging findings. To the best of our knowledge, this is the third case of GC presenting with blindness. The patient was a 35 years-old male in a drug rehabilitation center for heroin addiction. He presented with a headache, a single episode of seizure, and a 2-month history of bilateral decrease in visual acuity, which had acutely worsened. Magnetic resonance imaging (MRI) and computed tomography (CT) showed bilateral temporal lobe involvement. Ophthalmological studies showed bilateral papilledema, absence of visual evoked potential, and thickening of the retinal nerve fiber layer. Due to this clinical presentation, normal laboratory data, and suspicious MRI findings, further investigation with magnetic resonance spectroscopy (MRS) was performed. Results showed a greatly increased ratio of choline to creatinine(Cr) or N-acetyl aspartate (NAA), suggesting a neoplastic nature of the disease. Subsequently, the patient was referred for a brain tissue biopsy with a suspicion of malignancy. The pathology results revealed adult-type diffuse glioma with isocitrate dehydrogenase (IDH) mutation. Bilateral blindness, as well as bilateral temporal lobe involvement, each has many different causes. However, as demonstrated in this study, adult-type diffuse glioma must be considered a rare cause of concomitant bilateral temporal lobe involvement and blindness.

An enduring debate on gliomatosis cerebri.

Gliomatosis cerebri (GC) is a unique glial tumor that extensively invades the cerebral white matter and has been recognized as an entity of neuroepithelial tumors since the first edition of the WHO classification of brain tumors in 1979. Thereafter, in the fourth edition of the WHO classification in 2007, it was clearly defined as a specific type of astrocytic tumor. However, in the WHO 2016 classification, which was based on the concept of integrated diagnosis using molecular genetics, GC was deleted as it was considered to be only one growth pattern of diffuse glioma and not a specific pathological entity. Since then, there has been criticism by many neuro-oncologists and the establishment of the GC working group at the NIH, and many activities in the world arguing that GC should not be deleted from the clinical discussion of brain tumors. In Japan, positive activities toward multicenter research on GC pathology should be performed, and molecular pathological evidence that can contribute to the WHO classification in the future should be developed. In this article, the author outlined the pathological characteristics of GC, which has been repeated changing since its conception, and also describes his opinion on GC as a neuro-oncologist.

Clinical characteristics and radiological features of glioblastoma, IDH-wildtype, grade 4 with histologically lower-grade gliomas.

The 2021 World Health Organization (WHO) classification of central nervous system tumors applied molecular criteria and further integrated histological and molecular diagnosis of gliomas. This classification allows for the diagnosis of isocitrate dehydrogenase wild-type (IDHwt) glioblastoma (GBM), and WHO grade 4 with histologically lower-grade gliomas (LrGGs), even in the absence of high-grade histopathologic features, such as necrosis and/or microvascular proliferation. They contain at least one of the following molecular features: epidermal growth factor receptor amplification, chromosome 7 gain/10 loss, or telomerase reverse transcriptase promoter mutation. In the imaging features at the time of histological diagnosis, a gliomatosis cerebri growth pattern was frequently observed in these tumors. Furthermore, this growth pattern was significantly higher in IDHwt GBM, WHO grade 4, with histological grade II gliomas. Although the exact prognosis of IDHwt GBM, WHO grade 4, with histologically LGGs remains unknown, its OS was approximately 1-2 years similar to that of histologically IDHwt GBM, WHO grade 4, despite histopathological features similar to IDHmut LrGGs. These findings reinforce the need for the analysis of molecular features, regardless of presenting similar clinical characteristics and imaging features to IDHmut LrGGs.

Case report: durable response of gliomatosis cerebri with concurrent tumor-treating fields (TTFields) and chemoradiotherapy treatment.

BACKGROUND: Gliomatosis cerebri (GC) is a rare and aggressive form of widely disseminated glioma infiltrating at least 3 lobes of the brain. It is a diffuse pattern of growth seen in glioma rather than a distinct pathological diagnosis based on new Word Health Organization (WHO) classification. Despite this, it is associated with worse prognosis than equally graded gliomas. Tumor treating fields (TTFields) treatment is a more recent advancement in glioma treatment delivered through low energy, intermediate frequency (200 kHz) electromagnetic fields, with multi-modal mechanisms of action. It is Food and Drug Administration (FDA) approved for newly diagnosed and recurrent glioblastoma (GBM). The aim of this case report is to present a durable response of GBM associated GC to concurrent TTFields with chemoradiation. CASE DESCRIPTION: We report a 64-year-old male with left parietal GBM, IDH wild type, WHO grade 4 with extensive GC change. After resection of the enhancing lesion, the patient received concurrent tumor-treating fields (TTFields) with radiation and temozolomide, enrolled in SPARE trial (NCT03477110). The patient had a rapid response in the areas of gliomatosis change demonstrated on the magnetic resonance imaging 1 month post-radiation treatment. The response of GC was durable. His glioma recurred 11 months after surgery with new enhancing lesions, treated with radiosurgery. He had further extensive progression of enhancing lesions 13 months after surgery, and received bevacizumab treatment. The patient ultimately passed away 17 months after surgery. Despite progression of enhancing lesions, the GC changes remained controlled. He also had favorable progression-free survival of 11 months and overall survival of 17 months. CONCLUSIONS: This case serves as an example of how combination TTFields with chemoradiation may elicit a durable response of GC in patients with GBM.

Glioblastoma with Gliomatosis Cerebri Growth Pattern Presenting as Rapidly Progressive Dementia.

The differential diagnosis of rapidly progressive dementia includes neurodegenerative, toxic/metabolic, infectious, inflammatory, vascular, and malignant etiologies. This case highlights a patient with rapidly progressive cognitive decline that remained a diagnostic dilemma due to nonspecific symptoms of disorientation that progressed to persistent alteration in mental status over the span of three months. Routine laboratory testing did not help clarify the diagnosis and initial brain imaging showed only subtle abnormalities that were not commensurate with the patient's neurologic examination. As imaging findings evolved over time to reveal a multifocal process, a biopsy was pursued, with histology consistent with infiltrating glioma and molecular testing consistent with glioblastoma. Glioblastoma with gliomatosis cerebri growth pattern should be considered on the differential diagnosis of rapidly progressive dementia in patients with multifocal imaging findings.

T2/FLAIR Hyperintensity in Mesial Temporal Lobe: Challenging Differential Diagnosis.

T2/FLAIR hyperintensity in the mesial temporal lobe is the most common MR finding of herpes simplex encephalitis, but may be observed in other infectious and non-infectious diseases. The former includes herpes human virus 6 encephalitis, Japanese encephalitis, and neurosyphilis, and the latter autoimmune encephalitis, gliomatosis cerebri, bilateral or paradoxical posterior cerebral artery infarction, status epilepticus, and hippocampal sclerosis. Thus, T2/FLAIR hyperintensity in the mesial temporal lobe is not a disease-specific magnetic resonance imaging finding, and these conditions must be differentiated to ensure proper treatment. We review diseases that present with T2/FLAIR hyperintensity in the mesial temporal lobe and provide a helpful flow chart based on clinical and radiologic features.

A rare case of gliomatosis cerebri lurking beneath the shadows of a stroke mimic.

Gliomatosis cerebri (GC) is a diffuse infiltrative neoplastic glial process with a devastating prognosis. Considering its rarity, unpredictable clinical manifestations, and lack of characteristic radiographic features, GC is a difficult diagnosis that is quite often delayed. In this report, we present a case of a 61-year-old man with a history of chronic alcohol abuse and atrial fibrillation who presented with right arm weakness initially presumed to be from an acute ischemic stroke. GC was not diagnosed until six months after initial symptoms and diagnosis was indicated when considering the neurocognitive findings in conjunction with suggestive radiographic findings. The presence of a rapid, expansile lesion in the cortex, corpus callosum, and infratentorial structures with mild parenchymal enlargement, as shown in our case, is more revealing of an invasive entity typical of GC rather than an ischemic process and other pathologies. This case demonstrates the fatal challenges of its prompt recognition and the therapeutic limitations for those patients presenting with advanced symptoms at the time of diagnosis. Recognizing GC in cases with such rapid multilobe clinical features with similar diffusely invasive patterns of growth on imaging can avoid a delay in diagnosis and improve patient quality of life.

Gliomatosis Cerebri Growth Pattern: Association of Differential First-Line Treatment with Overall Survival in WHO Grade II and III Gliomas.

INTRODUCTION: Gliomatosis cerebri (GC) is defined by diffuse, widespread glial tumor growth affecting three or more cerebral lobes. Previous studies in gliomas found no distinct histological or molecular GC subtype, yet the presence of GC is associated with worse median overall survival (OS). Here, we explored whether differing therapeutic strategies in first-line treatment could account for this. METHODS: From our University Cancer Center database, 47 patients with histological diagnosis of WHO grade II or III glioma and GC imaging pattern were identified. GC criteria were confirmed by independent review. Patients with WHO grade II or III glioma with non-GC pattern served as control cohort (n = 343). RESULTS: Within the GC patient cohort, lower WHO grade, mutated isocitrate dehydrogenase 1 (IDH1) status, and absence of contrast enhancement were associated with better OS. Compared to the control cohort, patients with GC had significantly shorter OS independent of histological diagnosis or IDH1 mutation status. Patients with GC preferentially received chemotherapy alone (62 vs. 18%), and less frequently radiochemotherapy (21 vs. 27%). OS was significantly shorter in the GC cohort compared to the non-GC cohort both for chemotherapy (3.9 vs. 7.6 years, p = 0.0085) and for combined radiochemotherapy (1.1 vs. 8.4 years, p < 0.0001). However, when only patients who received biopsy plus chemotherapy were analyzed, the differences lost statistical significance (3.5 vs. 6.6 years, p = 0.196). CONCLUSION: We found major differences in the selection of first-line therapies of GC versus non-GC patients. Our results suggest that these differences may partly account for the worse prognosis of GC patients.

Leber's hereditary optic neuropathy with diffuse white matter changes mimicking gliomatosis cerebri: illustrative case.

BACKGROUIND: Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by bilateral severe subacute central vision loss and a mutation in the mitochondrial DNA (mtDNA). The findings on cranial magnetic resonance imaging of patients with LHON vary from subtle to multiple white matter changes. However, they rarely present with diffuse infiltrative white matter changes. OBSERVATIONS: The authors reported a case with diffuse white matter changes mimicking gliomatosis cerebri (GC). The histological findings included only mild glial hyperplasia without immunohistochemical positivity, supporting the diagnosis of glial tumors. Analysis of mtDNA obtained from the blood and brain tissue revealed mutation of m.11778G>A in the NADH dehydrogenase 4 gene, which confirmed the case as LHON. Immunohistochemistry of the brain tissue revealed 8-hydroxy-2'-deoxyguanosine positivity, suggesting the presence of oxidative stress. LESSONS: LHON is extremely difficult to diagnose unless one suspects or knows the disease. The present case brings attention not only to LHON but also to other mtDNA-mutated diseases that need to be considered with diffuse white matter changes or GC.

Canine Gliomatosis Cerebri: Morphologic and Immunohistochemical Characterization Is Supportive of Glial Histogenesis.

Gliomatosis cerebri (GC) is a glioma subtype with diffuse neuroparenchymal infiltration without architectural distortion. GC was first used in human neuropathology and remained controversial until its elimination from the diagnostic lexicon in 2016. GC is currently defined as a diffuse growth pattern of glioma rather than a distinct entity. In this article, we characterize 24 cases of canine GC and classify these neoplasms as diffuse gliomas. Selected cases of canine GC were reviewed and immunolabeled for oligodendrocyte lineage transcription factor 2 (Olig2), glial fibrillary acidic protein (GFAP), and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase). The mean age of affected dogs was 7 years, and 9 were brachycephalic. Gross lesions (8 cases) consisted mainly of parenchymal swelling. Histologically, of the 24 cases, there was widespread infiltration of neoplastic cells with astrocytic (12 cases), oligodendroglial (8 cases), or mixed morphology (4 cases) in the brain (18 cases), spinal cord (4 cases), or both (2 cases). Secondary structures occurred across different tumor grades and were not restricted to high-grade neoplasms. Astrocytic neoplasms had moderate nuclear immunolabeling for Olig2 and robust cytoplasmic immunolabeling for GFAP. Oligodendroglial neoplasms had robust nuclear immunolabeling for Olig2, moderate or absent cytoplasmic immunolabeling for GFAP, and moderate cytoplasmic immunolabeling for CNPase. Tumors with mixed morphology had robust nuclear immunolabeling for Olig2 and variable cytoplasmic immunolabeling for GFAP and CNPase. Morphologic and immunohistochemical features confirmed a glial histogenesis for all tumors and allowed for their classification as diffuse, low- or high-grade astrocytoma; oligodendroglioma; or undefined glioma. Further research is needed to confirm or refute the hypothesis that canine GC represents an infiltrative growth pattern of canine glioma.

Predictive factors for overall survival in surgical cases of gliomatosis cerebri from the National Cancer Database.

Gliomatosis Cerebri (GC) is a rare, aggressive, diffusely infiltrating cerebral tumor. Prognostic indicators and management strategies are currently poorly characterized. The National Cancer Database was queried for patients with histologically confirmed GC between 2004 and 2016. Demographic, tumor, and treatment characteristics were collected, including the Charlson/Deyo score, a comorbidity index adapted from the Charleston Comorbidity Index. Allowable values for the Charlson/Deyo score are 0 (no recorded comorbidities), 1, 2, and 3+ (most severe). Factors associated with overall survival were identified via bivariate log-rank tests and multivariate stepwise Cox proportional hazards models. The query returned 108 GC patients. The median age was 60.0 years, males were predominantly affected (63%), and most patients were white (86%). While 12% of cases achieved near/gross total resection and 27% of cases achieved partial resection, most surgeries were for biopsy (61%). Treatments included radiation therapy in 64% and chemotherapy in 63% of patients. The median overall survival was 15.1 (95% confidence interval [CI] = 11.1-24.8) months. On bivariate analysis, chemotherapy improved overall survival (p = 0.01) while radiation therapy (p = 0.07) and extent of resection (p = 0.48) did not. On multivariate analysis, older patients (hazard ratio [HR] = 1.07, CI = 1.03-1.11, p < 0.01) and Charlson/Deyo scores of ≥1 versus 0 (HR = 3.47, CI = 1.40-8.60, p < 0.01) had significantly increased mortality risk following surgery. In particular, the Charlson/Deyo score is a novel prognostic factor for GC that may guide clinical and surgical decision-making for this rare, rapidly fatal tumor. Further prospective studies are warranted to clarify the effects of chemotherapy versus radiation as treatment modalities for GC.

Gliomatosis cerebri mimicking diffuse demyelinating disease: Case Report.

Gliomatosis Cerebri (GC) is a rareand rapidly progressive pattern of growth of diffusely infiltrating gliomas with limited treatment options. Imaging findings are usually nonspecific and can mimic other neurologic disorders, including demyelination, encephalitis, and multicentric/multifocal glioma. In this report, we describe a case of a 53-year-old female who presented with left hemiparesis, global headache, and gait ataxia with imaging features initially thought to represent demyelinating disease. A combination of conventional and advanced imaging findings with brain biopsy was utilized to make the diagnosis of GC. In patients with widespread abnormalities on brain imaging, GC should strongly be considered when cortical expansion, involvement of the septum pellucidum and elevated myoinositol levels are observed and the clinical and laboratory findings are atypical for demyelination or infection. Considering GC in such cases can facilitate early biopsy with prompt diagnosis and avoid delay in appropriate treatment.

Gliomatosis cerebri and Rasmussen's encephalitis: Two different entities causing refractory epilepsy. Comparison through two clinical cases.

BACKGROUND AND IMPORTANCE: Rasmussen's Encephalitis (RE) is a chronic and progressive childhood disease caused by an inflammatory disorder that affects a cerebral hemisphere. On the other hand, Gliomatosis Cerebri (GC) is a rare primary neoplastic glial process with a diffuse and infiltrative growth. CLINICAL PRESENTATION: We present two clinical cases with a history of continuous focal epilepsy refractory to antiepileptic drugs. They share similar clinical and radiologic features, but a different histopathological diagnosis. A brain biopsy was needed to distinguish GC from a RE. CONCLUSION: The debut of a drug-resistant epilepsy with focal seizures and an ipsilateral progressive hemiparesis suggests the diagnosis of RE. However, there are other entities such as GC, which, despite its rarity, should be considered in the differential diagnosis. So, in some cases, histological diagnosis is needed.

Mortal consequences of a cooperative action between Takotsubo syndrome and increased intracranial pressure.

An elderly patient with head injury was registered to the emergency room. Because the patient arrived to the hospital unconscious, her cranial, cerebrovascular, and cardiac function was studied. The cardiac function measurements were (i) heart rate, (ii) blood pressure, (iii) oxygen saturation level, (iv) electrocardiogram (ECG), (v) coronary angiogram, (vi) chest computerized tomography (CT), and (vii) echocardiogram. The head damage was studied by cerebral CT and magnetic resonance imaging (MRI). The serum ischemia and inflammatory biomarkers were analysed. For the immediate treatment, the patient received cardiovascular system supporting medication. The cardiac diagnostic results were (i) the ECG suggested an elevation in the left ventricular systolic function, (ii) the blood test showed neutrophilia, increased creatine and increased troponin I kinase values, and (iii) the coronary angiogram and ECG analysis demonstrated a lack of a myocardial infarction but identified apical akinesia. The patient did not have previous symptoms of cardiovascular disease. The brain imaging demonstrated (iv) an acute ischemia in the left occipital area and (v) increased intracranial pressure. Brain MRI indicated (vi) aqueductal stenosis and (vii) multiple gliomatotic foci demonstrating hydrocephalus caused by gliomatosis cerebri. A chest CT indicated (viii) chronic obstructive pulmonary disease (COPD). One week later, the patient died because of cardiac arrest. The diagnosis was Takotsubo syndrome enforced by gliomatosis cerebri and COPD. To our knowledge, this is the first reported case in which the cardiac dysfunction of the patient is associated with gliomatosis cerebri-derived hydrocephalus and increased intracranial pressure that together with COPD may have enhanced the negative clinical outcome.

Gliomatosis cerebri (GC) or GC-like? A picture to be reconsidered in neuro-oncology based on large retrospective analysis of GC series.

INTRODUCTION: Gliomatosis cerebri (GC), defined until 2016 as a distinct astrocytic glioma entity, has been removed from the 2016 World Health Organization classification of tumors of the central nervous system. However, its identity is still debated. MATERIALS AND METHODS: We retrospectively present 122 patients, including a subgroup with histology confirmation (n = 75, cohort b). RESULTS: Radiological features showed extension limited to 3 lobes in 31%; bilateral, midline, and basal ganglia and subtentorial involvement in 95%, 52%, 84%, and 60%, respectively; and contrast enhancement in 59.5%. Perioperative mortality occurred in 4%. Histology concluded for grades II, III, and IV, respectively, in 31%, 35%, and 22% (not specified in 12%). Thirty-one percent had isocitrate dehydrogenase (IDH) 1 mutation. Treatments included radiotherapy in 51.2% and chemotherapy in 74.5%. Median overall survival was 17 months. Negative prognostic factors for survival were older age, poorer Karnofsky Performance Scale (KPS), subtentorial, midline and disseminated disease, and lack of chemotherapy, at univariate analysis. At multivariate analysis, KPS ≥ 80, chemotherapy, and subtentorial and disseminated disease remained prognostic (p < 0.0001). For cohort b, same prognostic factors were confirmed, except for midline location, at univariate analysis; at multivariate analysis, only KPS ≥ 80 and chemotherapy remained prognostic (p < 0.0001). CONCLUSION: We described clinical, neuroimaging, management, and histomolecular features of one of the largest GC series. We identified KPS ≥ 80, radiological pattern as subtentorial localization and dissemination, and chemotherapy as prognostic factors, at multivariate analysis. Planning prospective study, associated to focused genetic assays, could help to clarify if GC has specific features that may result in the identification as a separate entity from other gliomas.

Adult H3K27M-mutant diffuse midline glioma with gliomatosis cerebri growth pattern: Case report and review of the literature.

INTRODUCTION: H3K27M-mutant diffuse midline glioma is a recently classified unique entity predominantly affecting pediatric patients and rarely adults. The clinicopathologic features in adults remain poorly characterized. PRESENTATION OF CASE: A 36-year-old man presented with subacute progressive cognitive and visual deterioration, and hydrocephalus requiring ventricular shunting. MRI revealed a diffusely infiltrating lesion with a gliomatosis cerebri growth pattern, multiple foci of contrast enhancement, and diffuse leptomeningeal involvement. Suboccipital craniotomy with exploration of the posterior fossa revealed a subtle capsular lesion infiltrating into the choroid plexus. Although histologically low-grade, the tumor was found to have an H3K27 M mutation establishing the diagnosis. DISCUSSION: In spite of diverse clinicopathologic characteristics, H3K27M-mutant diffuse midline gliomas are incurable, WHO grade IV lesions with poor prognosis. We discuss our case in the context of a review of published reports of H3K27-mutant diffuse midline gliomas in adults. Findings late in the disease course may mimic inflammatory or infectious pathologies radiographically, and low-grade infiltrative neoplasms histologically. CONCLUSION: The diverse clinical, radiographic and molecular features of H3K27M-mutant diffuse midline gliomas in adults remain to be completely characterized. A high index of suspicion is required to avoid missing the diagnosis. Early biopsy and detailed molecular characterization are critical for accurate diagnosis and patient counseling.