[Clinicopathological characteristics and prognosis of diffuse midline gliomas with histone H3K27M mutation: an analysis of 30 cases].

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients' clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P=0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline (P>0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs (P>0.05). Conclusions: DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.

A Cascaded Deep Convolutional Neural Network for Joint Segmentation and Genotype Prediction of Brainstem Gliomas.

GOAL: Automatic segmentation of brainstem gliomas and prediction of genotype (H3 K27M) mutation status based on magnetic resonance (MR) images are crucial but challenging tasks for computer-aided diagnosis in neurosurgery. In this paper, we present a novel cascaded deep convolutional neural network (CNN) to address these two challenging tasks simultaneously. METHODS: Our novel segmentation task contains two feature-fusion modules: the Gaussian-pyramid multiscale input features-fusion technique and the brainstem-region feature enhancement. The aim is to resolve very difficult problems in brainstem glioma segmentation. Our prediction model combines CNN features and support-vector-machine classifier to automatically predict genotypes without region-of-interest labeled-MR images and is learned jointly with the segmentation task. First, Gaussian-pyramid multiscale input feature fusion is added to our glioma-segmentation task to solve the problems of size variety and weak brainstem-gliomas boundaries. Second, the two feature-fusion modules provide both local and global contexts to retain higher frequency details for sharper tumor boundaries, handling the problem of the large variation of tumor shape, and volume resolution. RESULTS AND CONCLUSION: Experiments demonstrate that our cascaded CNN method achieves not only a good tumor segmentation result with a high Dice similarity coefficient of 77.03%, but also a competitive genotype prediction result with an average accuracy of 94.85% upon fivefold cross-validation.

Progression of atypical extraventricular neurocytoma to anaplastic ganglioglioma.

We report a childhood case of thalamic atypical extraventricular neurocytoma that progressed to highly anaplastic ganglioglioma after 8 years of dormancy after subtotal resection and chemotherapy. The neurocytoma displayed immunoreactivity only for synaptophysin, ß-catenin, S100, and CD56. The ganglioglioma acquired strong immunoreactivity for chromogranin, glial fibrillary acidic protein, neuron-specific enolase, and p53 and showed a very high proliferation rate approaching 50% in some areas. Tumor transformation was associated with overexpression of components of the sonic hedgehog and Wnt developmental signaling pathways, which are known to regulate tumor-initiating cells in malignant brain neoplasms.

Morphologic characteristics and immunohistochemical profile of diffuse intrinsic pontine gliomas.

Tumors of the central nervous system are the second most common malignancy in children. In particular, diffuse intrinsic pontine gliomas (DIPGs) are aggressive tumors with poor prognosis and account for 10% to 25% of pediatric brain tumors. The majority of DIPGs are astrocytic, infiltrative, and localized to the pons. Studies have shown median survival times of less than a year, with 90% of children dying within 2 years. We built multitissue arrays with 24 postmortem DIPG samples and analyzed the morphology and expression of several proteins (p53, EGFR, GFAP, MIB1, BMI1, ß-catenin, p16, Nanog, Nestin, OCT4, OLIG2, SOX2) with the goal of identifying potential treatment targets and improving our understanding of the biology of these tumors. The majority of DIPGs were high-grade gliomas (22), with 18 cases having features of glioblastoma (World Health Organization [WHO] grade IV) and 4 cases with high-grade features consistent with anaplastic astrocytoma (WHO grade III). One case was low grade (WHO grade II), and 1 case showed intermediate features between a grade II and grade III glioma (low mitotic rate but increased cellularity and cell atypia), being difficult to grade precisely. The majority of the tumors were positive for GFAP (24/24), MIB1 (23/24), OLIG2 (22/24), p16 (20/24), p53 (20/24), SOX2 (19/24), EGFR (16/24), and BMI1 (9/24). Our results suggest that dysregulation of EGFR and p53 may play an important role in the development of DIPGs. The majority of DIPGs express stem cell markers such as SOX2 and OLIG2, consistent with a role for tumor stem cells in the origin and maintenance of these tumors. Targeted therapies against these proteins could be beneficial in treatment.

[Corpus callosum tumor as the presenting symptom of neurofibromatosis type 1 in a patient and literature review]. / Tumor del cuerpo calloso como presentación de neurofibromatosis tipo 1 en un paciente y revisión de la bibliografía.

INTRODUCTION: Neurofibromatosis type 1 (NF1) is one of the most frequent neurocutaneous syndromes. NF1 can be associated with intracranial tumors in any location, but only rarely in the corpus callosum. AIMS: To describe a case of NF1 presenting as a tumor of the corpus callosum and to carry out a review of the incidence of the tumors of corpus callosum in our series and in the literature. CASE REPORT: We present a child who was studied since 3 years of age because of complete NF1 clinical diagnostic criteria (without genetic study). He was studied by MR and magnetic resonance spectroscopy (MRS). MR study showed neurofibromatosis bright objects distributed over several regions of the cerebral hemispheres and cerebellum, a possible brain stem tumor (bulbar zone) and the splenium of the corpus callosum. The MRS of the brain stem tumor showed changes consistent with a low grade glial tumor. The patient was followed until 19-years of age without demonstrating any changes in the clinical features or the tumor size in both locations Only six cases of corpus callosum tumor in patients with NF1 have been published to date. CONCLUSIONS: We present a new case with tumor of the corpus callosum and NF1. The imaging characteristics and the clinical course were in favour of the benign nature of this type of tumor.

Malignant pilocytic astrocytoma in the medulla oblongata: case report.

A 27-year-old woman visited our hospital with chief complaints of abducens nerve palsy and cerebellar symptoms. On computerized tomographic scanning and magnetic resonance imaging, a tumor with strong enhancement was found on the dorsal side of the medulla oblongata. A tumor was excised by suboccipital craniotomy and C1 laminectomy. Histologically, many Rosenthal fibers together with pilocytic tumor cells were found in some regions, but a very high Ki-67 labeling rate accompanied by cells with nuclei of irregular size and giant cells was observed in other regions. The tumor was diagnosed as malignant pilocytic astrocytoma originating from pilocytic astrocytoma by transformation. The biological behavior of pilocytic astrocytoma is obscure in several respects. We report our experience of a case of malignant pilocytic astrocytoma that developed in the brain stem and progressed extremely rapidly.