OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

Glioma is the most common and lethal intrinsic primary tumor of the brain. Its controversial origins may contribute to its heterogeneity, creating challenges and difficulties in the development of therapies. Among the components constituting tumors, glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation. Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor, in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation. Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states, glial, neural, and immune cell populations in the tumor microenvironment. Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy. Here, we discuss the heterogeneity and relevant functions of tumor cell state, microglia, monocyte-derived macrophages, and neurons in glioma, highlighting their bilateral effects on tumors. Finally, we describe potential therapeutic approaches and targets beyond standard treatments.
Humans ; Glioma/metabolism* ; Neuroglia/metabolism* ; Carcinogenesis/pathology* ; Neural Stem Cells/metabolism* ; Microglia/metabolism* ; Brain Neoplasms/metabolism* ; Tumor Microenvironment

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Adult ; Humans ; Rhabdoid Tumor/surgery* ; Teratoma/pathology* ; Medulloblastoma ; Central Nervous System Neoplasms ; Cerebellar Neoplasms ; Brain Neoplasms/pathology*

OBJECTIVE: To study the clinical features of children with recurrent medulloblastoma (MB) and treatment regimens. METHODS: A retrospective analysis was performed on 101 children with recurrent MB who were admitted to the hospital from August 1, 2011 to July 31, 2017. The children were followed up to July 31, 2020. The Kaplan-Meier method was used for survival analysis. The Cox regression model was used for multivariate regression analysis. RESULTS: Of the 101 children, 95 underwent remission induction therapy, among whom 51 had response, resulting in a response rate of 54%. The median overall survival (OS) time after recurrence was 13 months, and the 1-, 3-, and 5-year OS rates were 50.5%±5.0%, 19.8%±4.0%, and 10%±3.3% respectively. There was no significant difference in the 5-year OS rate between the children with different ages (< 3 years or 3-18 years), sexes, pathological types, or Change stages, between the children with or without radiotherapy before recurrence or re-irradiation after recurrence, and between the children with different times to recurrence (< 12 months or ≥ 12 months after surgery) ( CONCLUSIONS As for the recurrence of MB, although remission induction therapy again can achieve remission, such children still have a short survival time. Only reoperation can significantly prolong survival time, and therefore, early reoperation can be considered to improve the outcome of children with recurrent MB.
Cerebellar Neoplasms/therapy* ; Child ; Humans ; Medulloblastoma/therapy* ; Neoplasm Recurrence, Local ; Retrospective Studies ; Survival Rate

Lhermitte-Duclos disease (LDD) is a type of rare brain tumor located in posterior fossa. A patient with LDD located in the left cerebellum and vermis was admitted by the Department of Neurosurgery, Xiangya Hospital, Central South University. MRI scan showed slightly heterogeneous enhancement at the region close to vermis. The patient underwent partial resection on August 11, 2016 without postoperative chemoradiotherapy. The progress free survival was 11 months and the overall survival was 17 months. What the case reveals is that the partial resection is not beneficial to these patients with LDD as the residual lesion probably recurs in a short term after operation. The pathogenesis, diagnosis and treatment of LDD are explored and summarized in combination with relevant literature.
Cerebellar Neoplasms/surgery* ; Cerebellum ; Hamartoma Syndrome, Multiple/diagnostic imaging* ; Humans ; Magnetic Resonance Imaging ; Neoplasm Recurrence, Local

Primary hypothyroidism commonly occurs after radiotherapy (RT), and coincides with increased circulating thyroid-stimulating hormone (TSH) levels.We tested therefore the protective effect of suppressing TSH with L-thyroxine during RT for medulloblastoma/PNET and Hodgkin lymphoma (HL) in a prospective cohort study. From1998 to 2001, a total of 37 euthyroid children with medulloblastoma/PNET plus 14 with HL, scheduled for craniospinal irradiation and mediastinum/neck radiotherapy, respectively, underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of craniospinal iiradiation. From 14 days before and up to the end of radiotherapy, patients were administered L-thyroxine checking every 3 days TSH to ensure a value < 0.3 μIU/mL. During follow-up, blood tests and ultrasound were repeated; primary hypothyroidism was considered an increased TSH level greater than normal range. Twenty-two/37 patients with medulloblastoma/PNET and all the 14 patients with HL were alive after a median 231 months from radiotherapy with 7/22 and 8/14 having correctly reached TSH levels < 0.3 μIU/mL and well matched for other variables. Twenty years on, hypothyroidism-free survival rates differed significantly, being 60% ± 15% and 15.6% ± 8.2% in TSH-suppressed vs. not-TSH suppressed patients, respectively (P = 0.001). These findings suggest that hypothyroidism could be durably prevented in two populations at risk of late RT sequelae, but it should be confirmed in a larger cohort.
Cerebellar Neoplasms ; Child ; Hodgkin Disease/radiotherapy* ; Humans ; Hypothyroidism/prevention & control* ; Medulloblastoma/radiotherapy* ; Prospective Studies ; Thyrotropin

Anti-Ma2-associated encephalitis is one of the paraneoplastic limbic and brainstem encephalitis characterized by decreased consciousness, parkinsonism and the limitation of vertical eye movement. It is usually associated with non-small cell lung cancer in male and female or germ cell tumor in male. Herein, we report a case of atypical anti-Ma2-associated encephalitis which presented with axonal sensorimotor polyneuropathy.
Autoantibodies ; Axons ; Brain Stem ; Carcinoma, Non-Small-Cell Lung ; Consciousness ; Encephalitis ; Eye Movements ; Female ; Humans ; Limbic Encephalitis ; Male ; Neoplasms, Germ Cell and Embryonal ; Paraneoplastic Syndromes ; Parkinsonian Disorders ; Polyneuropathies

PURPOSE: The aim is to study the dependence of deformable based auto-segmentation of head and neck organs-at-risks (OAR) on anatomy matching for a single atlas based system and generate an acceptable set of contours. METHODS: A sample of ten patients in neutral neck position and three atlas sets consisting of ten patients each in different head and neck positions were utilized to generate three scenarios representing poor, average and perfect anatomy matching respectively and auto-segmentation was carried out for each scenario. Brainstem, larynx, mandible, cervical oesophagus, oral cavity, pharyngeal muscles, parotids, spinal cord, and trachea were the structures selected for the study. Automatic and oncologist reference contours were compared using the dice similarity index (DSI), Hausdroff distance and variation in the centre of mass (COM). RESULTS: The mean DSI scores for brainstem was good irrespective of the anatomy matching scenarios. The scores for mandible, oral cavity, larynx, parotids, spinal cord, and trachea were unacceptable with poor matching but improved with enhanced bony matching whereas cervical oesophagus and pharyngeal muscles had less than acceptable scores for even perfect matching scenario. HD value and variation in COM decreased with better matching for all the structures. CONCLUSION: Improved anatomy matching resulted in better segmentation. At least a similar setup can help generate an acceptable set of automatic contours in systems employing single atlas method. Automatic contours from average matching scenario were acceptable for most structures. Importance should be given to head and neck position during atlas generation for a single atlas based system.
Brain Stem ; Head and Neck Neoplasms ; Head ; Humans ; Larynx ; Mandible ; Methods ; Mouth ; Neck ; Organs at Risk ; Pharyngeal Muscles ; Radiotherapy ; Spinal Cord ; Trachea

A 74-year-old woman presented with a month-long nausea and vomiting, then she could not take a meal. She had found an asymptomatic 4th ventricular mass 6 year ago as a preoperative work-up for ovarian cancer. And during the yearly follow-up, the mass had grown continuously over 6 years, and caused symptoms in the seventh year. MRI revealed a large ovoid extra-axial mass in the fourth ventricle compressing adjacent medulla and cerebellum. Surgery achieved near total resection since the tumor tightly adhered to the brain stem of 4th ventricle floor. The histological diagnosis was ependymoma (WHO grade II). She transferred rehabilitation facility for mild gait disturbance, hoarseness and swallowing difficulty. Fourth ventricle ependymoma in the elderly is extremely rare and the growth rate has not been reported. Here, we present a rare care of 4th ventricle ependymoma found asymptomatic at elderly but continuously grow to cause local pressure symptoms.
Aged ; Brain Stem ; Cerebellum ; Deglutition ; Diagnosis ; Ependymoma ; Female ; Follow-Up Studies ; Fourth Ventricle ; Gait ; Hoarseness ; Humans ; Magnetic Resonance Imaging ; Meals ; Nausea ; Ovarian Neoplasms ; Rehabilitation ; Vomiting