Prognostic implications of immune-related eight-gene signature in pediatric brain tumors

Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors (PBT) that may lead to novel therapeutic strategies. Participants of the cohort Pediatric Brain Tumor Atlas: CBTTC (CBTTC cohort), were randomly divided into training and validation cohorts. In the training cohort, Kaplan-Meier analysis and univariate Cox regression model were applied to preliminary screening of prognostic genes. The LASSO Cox regression model was implemented to build a multi-gene signature, which was then validated in the validation and CBTTC cohorts through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. Also, gene set enrichment analysis (GSEA) and immune infiltrating analyses were conducted to understand function annotation and the role of the signature in the tumor microenvironment. An eight-gene signature was built, which was examined by Kaplan-Meier analysis, revealing that a significant overall survival difference was seen, either in the training or validation cohorts. The eight-gene signature was further proven to be independent of other clinic-pathologic parameters via the Cox regression analyses. Moreover, ROC analysis demonstrated that this signature owned a better predictive power of PBT prognosis. Furthermore, GSEA and immune infiltrating analyses showed that the signature had close interactions with immune-related pathways and was closely related to CD8 T cells and monocytes in the tumor environment. Identifying the eight-gene signature (CBX7, JADE2, IGF2BP3, OR2W6P, PRAME, TICRR, KIF4A, and PIMREG) could accurately identify patients' prognosis and the signature had close interactions with the immunodominant tumor environment, which may provide insight into personalized prognosis prediction and new therapies for PBT patients.

Recurrent Pituicytoma in a Pediatric Patient: A Case Report

Pituicytoma is a rare tumor that arises from the glial cells of the neurohypophysis. For a long time, it was believed that pituicytomas only appeared in adults. Currently, at least three cases of this entity occurring in children have been reported in the literature. The aim of the present report is to describe the case of a 5-year-old girl who presented to the emergency department with visual disturbances, and the diagnosis was a recurrent pituicytoma. Therefore, the clinical presentation, the radiological features of the tumor, and the corresponding surgical management are described. Additionally, a brief review of the management of this unusual entity was performed.

O pituicitoma é um tumor raro que surge das células gliais da neurohipófise. Durante muito tempo, acreditou-se que os pituicitomas só aparecessem em adultos. Atualmente, pelo menos três casos desta entidade ocorrendo em crianças foram relatados na literatura. O objetivo do presente artigo é descrever o caso de uma menina de 5 anos que chegou à emergência com distúrbios visuais, e o diagnóstico foi um pituicitoma recorrente. A apresentação clínica, as características radiológicas do tumor, e o correspondente manejo cirúrgico foram, portanto, descritos. Além disso, foi realizada uma breve revisão do tratamento desta entidade incomum.

Clinical Characteristics of Intracranial Germ Cell Tumors in Children / 임상소아혈액종양

BACKGROUND: Intracranial germ cell tumors are higher in the East Asia such as Korea and Japan than any other Western countries. By analyzing common clinical features of intracranial germ cell tumors in children, we will prevent from misdiagnosing and delaying in the establishment of diagnosis. Furthermore, we can choose appropriate therapeutic plans to improve patient's prognosis.METHODS: We retrospectively reviewed the medical records of 68 patients to investigate and analyze clinical characteristics of intracranial germ cell tumors in children.RESULTS: The average age of 68 patients was 14.8 years old, and the male to female ratio in all patients was 3:1. The most common symptom presented by 30 patients was headache regarded as a nonspecific symptom in brain tumors. Sixty four patients were diagnosed by histologic method called biopsy and most of them were come out into germinoma. Thirty five patients were included in low-risk group and 30 patients were in high-risk group. Intracranial germ cell tumors in this study were most commonly located in the pineal gland.CONCLUSION: There are a variety of types in intracranial germ cell tumors, and they have been accurately diagnosed by radiologic, histologic methods and elevated tumor markers. We concluded that it is necessary for early diagnosis to evaluate exhaustively in patients suspected of brain tumors.

Clinical Characteristics of Intracranial Germ Cell Tumors in Children / 임상소아혈액종양

BACKGROUND: Intracranial germ cell tumors are higher in the East Asia such as Korea and Japan than any other Western countries. By analyzing common clinical features of intracranial germ cell tumors in children, we will prevent from misdiagnosing and delaying in the establishment of diagnosis. Furthermore, we can choose appropriate therapeutic plans to improve patient's prognosis. METHODS: We retrospectively reviewed the medical records of 68 patients to investigate and analyze clinical characteristics of intracranial germ cell tumors in children. RESULTS: The average age of 68 patients was 14.8 years old, and the male to female ratio in all patients was 3:1. The most common symptom presented by 30 patients was headache regarded as a nonspecific symptom in brain tumors. Sixty four patients were diagnosed by histologic method called biopsy and most of them were come out into germinoma. Thirty five patients were included in low-risk group and 30 patients were in high-risk group. Intracranial germ cell tumors in this study were most commonly located in the pineal gland. CONCLUSION: There are a variety of types in intracranial germ cell tumors, and they have been accurately diagnosed by radiologic, histologic methods and elevated tumor markers. We concluded that it is necessary for early diagnosis to evaluate exhaustively in patients suspected of brain tumors.

Glioblastoma pediátrico: estudo clínico patológico de 12 casos com imunoistoquímica para proteína p53 / Pediatric glioblastoma: a clinicopathological study of 12 cases with p53 protein immunohistochemistry

Glioblastoma é um dos tumores primários mais letais do sistema nervoso central (SNC). Apesar dos significativos progressos, há poucas análises em crianças. Com o objetivo de avaliar localização, idade, sexo, sobrevida e imunoistoquímica para proteína p53, foram coletados casos de glioblastomas pediátricos do "Banco de Tumores do SNC de Curitiba", durante 1987-2003 e do Hospital Municipal Jesus, Rio de Janeiro, de 1970 a 1988. Doze preencheram os critérios de inclusão. A idade variou até 12 anos (média 7), sendo sete do sexo feminino e cinco do masculino. A sobrevida média foi 7,9 meses. Localizavam-se em hemisférios cerebrais (58,4 por cento), mesencéfalo e tronco (33,3 por cento) e um no cerebelo. A imunoistoquímica demonstrou p53 positivo em 9 (75 por cento). Em conclusão, glioblastoma tem comportamento semelhante entre crianças e adultos, sendo nestas menos freqüentes. Acomete hemisférios cerebrais com maior freqüência que estruturas infratentoriais, mostrando alta sensitividade com a imunomarcação para proteína p53, sendo nestes casos mais agressivos, com menor sobrevida.

Glioblastoma is one of the most lethal central nervous system (CNS) primary tumor. Although significant progress, only few analysis have been made in pediatric glioblastoma, which are less common and have worse prognosis than in adults. To evaluate gender, site, age, survival, and immunohistochemistry to p53, we selected cases of pediatric glioblastoma of "CNS Tumors Database in Curitiba", 1987-2003 and of the Hospital Municipal Jesus, Rio de Janeiro, 1970-1988. Twelve tumors were included. The age ranged from up to 12 years (median 7). There were 7 females and 5 males. The median survival was 7.9 months. Location was: cerebral hemispheres (58.4 percent), mesencephalon and brainstem (33.3 percent) and one case in the cerebellum. Immunostained to p53 in 9 (75 percent) cases. In conclusion, glioblastoma behaves similarly in children and adults. It is rare in children, affects both cerebral hemispheres more than brainstem and cerebellum and shows strong immunohistochemistry to p53.

Results of Treatment for Children with Primary Brain Tumors: Long-Term Follow Up Results of a Single Institute

PURPOSE: Brain tumors are the most common solid tumor in children. We retrospectively investigated the clinical characteristics of pediatric brain tumors, such as age, sex, tumor site and survival, as seen in a single institution over the last 15 years. We tried to evaluate the role of chemotherapy on the survival of some brain tumors. METHODS: Three hundred fifty four children with primary brain tumor who were treated at Severance Hospital from Jan. 1985 to Sep. 2001 were enrolled. RESULTS: Pediatric brain tumors were found most frequently in 10-15 years of age group(35.3%) and the ratio of male to female was 1.3 : 1. Supratentorial tumors(52%) were more frequent than infratentorial tumors(48%). Medulloblastoma/primitive neuroectodermal tumor(PNET) was the most common type(24.6%), followed by cerebellar astrocytoma(14.1%). Ten year survival rate of medulloblastoma, cerebellar astrocytoma and cerebral astrocytoma were 59.4%, 79.3% and 71%, respectively. The prognosis for brain stem glioma and glioblastoma multiforme were still grim with a 10 year survival rate of 12.7% and 13.3%, respectively. The addition of chemotherapy for high grade medulloblastoma led to an improved 10 year survival rate of 54.5%, compared with 40% without chemotherapy. CONCLUSION: The combined use of chemotherapy and radiation and surgery improved survival rate of pediatric brain tumors in our study. Chemotherapy for high grade medulloblastoma improved the 10 year survival rate. Further data analysis of the treatment modalities will lead to better comparisons.

Posterior Fossa Tumors in Children

The authors reviewed retrospectively the records of 27 cases of posterior fossa tumor in patients below the age of 60 among the 387 brain tumor cases admitted to Kyungpook University Hospital during the last 10 years. The posterior fossa tumors were 34.2% of the total 79 cases of pediatric brain tumors. The most frequently involved age group was 6~8 years. Headache(40.7%) and vomiting(37.0%) were the most common initial presenting symptoms. Cerebellar signs, Cranial nerve palsy and motor weakness were found in 66.7%, 9.6% and 11.1% of the cases respectively. Cerebellar midline was the most frequently involved site(63.0%). In order of frequency, the pathological diagnoses were medulloblastoma, ependymoma, primitive neuroectodermal tumor(PNET), and astrocytoma. Hydrocephalus was noted in 70.4%, and shunt surgery was done in 28.6%. Surgery followed by radiation therapy was used in most of the cases.

A Clinical Analysis of Brain Tumors in Children

The authors performed a clinical analysis of 80 cases of pediatric brain tumors which were verified by surgical operation during 10 years from Sept. 1978 to Aug. 1987 in the Department of Neurosurgery, Korea University, Seoul, Korea. These tumors were divided according to modified WHO classification. The results were as follows: 1) The male to female ratio was 1.42:1. 2) The most common pediatric brain tumor was gliomas(48.7%), and followed by medulloblastome(17.5%), germ cell tumor(7.5%), craniopharyngioma(6.2%), meningioma(5.0%). 3) Supratentorial tumors(57.5%) were more frequent than infratentorial tumors(42.5%). 4) Headache and vomiting were the most common presenting symptoms and papilledema was the most common sign. 5) Hydrocephalus was developed at supratentorial(58.7%) and infratentorial(73.5%) region. 6) Postoperative mortality was 7%.

A Clinical Analysis of Brain Tumors in Children

The authors performed a clinical analysis of 80 cases of pediatric brain tumors which were verified by surgical operation during 10 years from Sept. 1978 to Aug. 1987 in the Department of Neurosurgery, Korea University, Seoul, Korea. These tumors were divided according to modified WHO classification. The results were as follows: 1) The male to female ratio was 1.42:1. 2) The most common pediatric brain tumor was gliomas(48.7%), and followed by medulloblastome(17.5%), germ cell tumor(7.5%), craniopharyngioma(6.2%), meningioma(5.0%). 3) Supratentorial tumors(57.5%) were more frequent than infratentorial tumors(42.5%). 4) Headache and vomiting were the most common presenting symptoms and papilledema was the most common sign. 5) Hydrocephalus was developed at supratentorial(58.7%) and infratentorial(73.5%) region. 6) Postoperative mortality was 7%.

Pediatric Cerebellopontine Angle Tumors

From 1957 to Jun 1987, authors experienced 8 cases of pediatric brain tumor located in the cerebellopontine angle(CPA) which were operated upon at the Department of Neurosurgery of Seoul National University Hospital. The proportion of the pediatric CPA tumors in the total pediatric brain tumors was 4% (8/197), and that in the pediatric posterior fossa tumors was 8% (8/100). The pathologic diagnoses of the 8 cases were ependymoma (2 cases), medulloblastoma (2 cases), astrocytoma ( 1 case), primitive neuroectodermal tumor (1 case), trigeminal schwannoma (1 case) and Masson's hemangioendothelioma (1 case). The proportion of CPA location in the posterior fossa ependymomas was 13% (2/16), and those of the posterior fossa medulloblastomas and astrocytomas were 4% (2/50 and 1/28, respectively). The initial presentations were symptoms of increased intracranial pressure in 5 cases, and those of cranial nerve dysfunction in 3 cases. On admission, all of 8 cases showed signs of increased intracranial pressure and among the cranial nerve dysfunctions, facial nerve dysfunction was most common (5 cases). It seemed that it was due to close relationship between these tumors and fourth ventricle, and the patients' age which was too young to complain of subtle subjective sensory dysfunctions. The operative findings showed medial displacement and compression of the cerebellum, brain stem and cranial nerves, enlargement of surrounding subarachnoid space or arachnoid cyst formation, tumor growth into the cranial nerve canals, and encasement of nerves or vessels by the tumor. The sites of origin were lateral recess of fourth ventricle in 4 cases (2 ependymomas and 2 medulloblastomas), and surrounding brain tissue in the other 2 glioma cases. And a representative case was presented.