Epidemiology, Clinical Presentation, and Prognosis of Pediatric Brain Tumors: Experience of National Center for Children’s Health

Objective Brain tumors have become the most common solid tumors in children. The epidemiology is poorly described in China. This retrospective study aimed to describe the epidemiologic characteristics, clinical presentation, and prognosis in national health center for children. Method From January 2015 to December 2020, 484 cases age 0-18 years old diagnosed with brain tumors and receiving neurosurgery treatment were enrolled into the database. Pathology was based on the World Health Organization 2012 nervous system tumor classification, and tumor behavior were classified on International Classification of Diseases for Oncology, third edition. A descriptive and comparative statistic was performed on clinical manifestation, symptom duration, sex, age, tumor location, tumor behavior, and survival time. Results Among the 484 brain tumors, the median age at diagnosis was 4.62 [2.19, 8.17] years old (4.07 [1.64, 7.13] for benign tumors and 5.36 [2.78, 8.84] for malignant tumors). The overall male to female ratios were 1.33:1, with 1.09:1 and 1.62:1 for benign and malignant tumors respectively. Nausea and vomiting, headache were the most frequent initial symptoms. The median symptoms duration was 4[2, 21] weeks. The three most frequent tumor type were embryonal tumors (22.45%), other astrocytic tumors (20.17%), and diffuse astrocytic tumors (11.02%). Supratentorial tumors comprise 57.38% of all brain tumors. And the most common tumor locations were cerebellum and forth ventricles (38.67%), sellar region (22.87%) and ventricles (10.60%). Male were more common among choroid plexus tumors (63.64%), embryonal tumors (61.11%), ependymal tumors (68.57%), and germ cell tumors (78.13%). Patients were followed for 1 to 82 months. The overall 5-year survival was 77.4%, with 90.0% for benign tumor and 65.3% for malignant tumors. log-rank test found significant different at p <0.001 level. Conclusion Brain tumors presented particularly sexual, age dependent, and regional dependent epidemiological characteristic. Our results were consistent with previous reports, and might reflect the real epidemiology status in China.

Expression of Anaplastic Lymphoma Kinase in Astrocytic Tumors (Histopathological and Immunohistochemical Study)

BACKGROUND: Astrocytic tumors are the most common primary brain tumors. Glioblastoma is the most common astrocytic tumor representing the highest World Health Organization (WHO) grade (WHO grade IV) with poor prognosis and short survival time. Anaplastic lymphoma kinase (ALK) has a role in embryonic central nervous system development. ALK receptor is thought to contribute to nervous system function, repair, and metabolic homeostasis and is expressed in high-grade tumors like anaplastic large cell lymphoma that makes it a potential target for therapeutic intervention. AIM: This work aimed to examine the immunohistochemical expression of ALK in astrocytic tumors and its correlation with age, sex, clinical presentation, location, laterality, recurrence, and WHO grade to implicate possible therapeutic potential. METHODS: This retrospective study was conducted on sixty cases of archived, formalin-fixed, paraffin-embedded tissue blocks that included different subtypes and grades of astrocytic tumors. Immunohistochemistry using ALK monoclonal antibody was performed using a standard avidin-biotin-peroxidase system. RESULTS: Of the sixty cases, 57 (95%) cases were negative for ALK, while three (5%) cases are positive for ALK; all showed the strong intensity of expression. No statistically significant association was found between ALK expression and astrocytic tumors in addition to other clinical variables of the studied tumors. CONCLUSIONS: Most cases of astrocytic tumors showed negative ALK expression apart from three positive cases seen in higher WHO grades, especially gliosarcoma. The high number of negative cases for ALK in our study group suggests that ALK expression is not associated with a prognostic significance toward astrocytic tumors whatever its grade.

Prognostic histopathologic features of canine glial tumors

Gliomas are relatively common tumors in aged dogs (especially brachycephalic breeds), and the dog is proving to be useful as a translational model for humans with brain tumors. Hitherto, there is relatively little prognostic data for canine gliomas and none on outcome related to specific histological features. Histologic sections of tumor biopsies from 33 dogs with glioma treated with surgical resection and immunotherapy and 21 whole brains obtained postmortem were reviewed. Tumors were diagnosed as astrocytic, oligodendroglial, or undefined glioma using Comparative Brain Tumor Consortium criteria. Putative features of malignancy were evaluated, namely, mitotic counts, glomeruloid vascularization, and necrosis. For biopsies, dogs with astrocytic tumors lived longer than those with oligodendroglial or undefined tumor types (median survival 743, 205, and 144 days, respectively). Dogs with low-grade gliomas lived longer than those with high-grade gliomas (median survival 734 and 194 days, respectively). Based on analysis of tumor biopsies, low mitotic counts, absence of glomeruloid vascularization, and absence of necrosis correlated with increased survival (median 293, 223, and 220 days, respectively), whereas high mitotic counts, glomeruloid vascularization, and necrosis correlated with poor survival (median 190, 170, and 154 days, respectively). Mitotic count was the only histological feature in biopsy samples that significantly correlated with survival ( P < .05). Whole-brain analyses for those same histologic features had similar and more robust correlations, and were statistically significant for all features ( P < .05). The small size of biopsy samples may explain differences between biopsy and whole-brain tumor data. These findings will allow more accurate prognosis for gliomas.

Ras, TrkB, and ShcA Protein Expression Patterns in Pediatric Brain Tumors

Numerous papers have reported altered expression patterns of Ras and/or ShcA proteins in different types of cancers. Their level can be potentially associated with oncogenic processes. We analyzed samples of pediatric brain tumors reflecting different groups such as choroid plexus tumors, diffuse astrocytic and oligodendroglial tumors, embryonal tumors, ependymal tumors, and other astrocytic tumors as well as tumor malignancy grade, in order to characterize the expression profile of Ras, TrkB, and three isoforms of ShcA, namely, p66Shc, p52Shc, and p46Shc proteins. The main aim of our study was to evaluate the potential correlation between the type of pediatric brain tumors, tumor malignancy grade, and the expression patterns of the investigated proteins.

IDH-Mutant Astrocytoma With Chromosome 19q13 Deletion Manifesting as an Oligodendroglioma-Like Morphology

Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1 mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1 or IDH2 mutations. These tumors also had chromosome 19q13 deletion, including the CIC gene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest that IDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CIC gene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.

Midline Astrocytic Tumors in Children: A Retrospective Study of 152 Cases

The aim of this study was to analyze the various midline structures having preponderance for astrocytoma, their incidence, clinical features, operative approach, prognosis, and outcomes in children. It is a retrospective analysis of 152 cases with midline astrocytic tumors in children admitted between January 1995 and December 2012 in the Department of Neurosurgery at Sanjay Gandhi Postgraduate Institute of Medical sciences Lucknow, India. The mean age of the cases with midline astrocytic tumors was 9.29 ± 4.56 years. Majority of these tumors occurred in the age group of 6 to 10 years (n = 58, 38.16%), with male to female ratio being 1.66:1. Out of 152 cases, tumors located at midline cerebellum constituted majority of the cases (n = 38, 25%) followed by brain stem (n = 28, 18.42%), thalamic region (n = 24, 15.79%), corpus callosum (n = 18, 11.82%), pineal region (n = 12, 7.89%), optic nerve (n = 12, 7.89%), chiasmo-hypothalamic (n = 10, 6.58%), and septum pellucidum astrocytomas (n = 10, 6.58%). Majority of these tumors were of low-grade type (n = 136, 89.47%), and pilocytic astrocytomas were the commonest subtypes. Out of 152 cases, 136 (89.47%) cases had improved outcomes, 8 (5.26%) remained as they were in preoperative state, and mortality was seen in 8 (5.26%) of the cases at 3 to 77 months (mean 26.70 ± 9.70) of follow-up. Midline structures having preponderance for astrocytomas were midline cerebellum, brain stem, thalamus, corpus callosum, pineal region, optic nerve, chiasmo-hypothalamic, and septum pellucidum. Cerebellum was the commonest site. Most of these astrocytomas were of low grade with pilocytic astrocytoma being the commonest subtype. With meticulous presurgical planning, most of these tumors have good outcome with significant reduction in mortality and morbidity.

NI-10 T2/FLAIR mismatch sign and methionine PET uptake in grade II and III gliomas

Background: Recent study suggests that “T2/FLAIR mismatch” sign is specific MRI finding for isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted gliomas (Grade II and III astrocytic tumors). T2/FLAIR mismatch sign may be useful for predicting the histological type of glioma before surgery. However, it is not known what this finding reflects. Therefore, we examined the correlation between T2/FLAIR mismatch sign and uptake of methionine with positron emission tomography (MET-PET), and molecular classification of glioma. Methods: 74 glioma patients (grade II: 30 cases, grade III: 44 cases) with preoperative MRI and MET-PET who underwent surgical resection during 2000–2019 were included in this study. MR scans were evaluated by 3 independent reviewers to assess presence/absence of T2/FLAIR mismatch sign. The tumor-to-normal (T/N) ratio of methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. We examined the relationship between IDH mutation, 1p/19q codeletion, mismatch, and T/N ratio of MET-PET. Results: Out of the 74 cases, astrocytic tumors (A group: IDH-mutant, 1p19q non-codeleted) were 21 (28%), oligodendroglial tumors (O group: IDH-mutant, 1p19q codeleted) were 19 (26%), and IDH wild tumors (W group) were 34 (46%). The T2/FLAIR mismatch sign was present in 16 cases (22%). The T/N ratio of MET-PET in the tumor with T2/FLAIR mismatch sign was 1.56, which was significantly lower than that in the tumor without mismatch sign (2.01, p=0.016). T2/FLAIR mismatch sign was found in 7 (33%) cases in the A group, 0 (0%) case in the O group and 9 (26%) cases in the W group, and the positive rate was significantly higher in the A group (p=0.013). Conclusions: “T2/FLAIR mismatch” sign was a specific finding for astrocytic tumor, and the cases with positive “T2/FLAIR mismatch” sign had significantly lower MET-PET uptake than that with negative cases.

Molecular and Cellular Mechanisms of Human Astrocytoma Progression: Advances in Knowledge to Reach Therapeutic Horizons

Human astrocytic tumors are primary central nervous system (CNS) tumors that arise either from astrocytes or from precursor cells. A growing number of epidemiological and incidence studies in different countries underlined that, in addition to increasing economic costs for health systems, these cancers are still representing one of the main hurdles in developing a successful therapeutic goal for patients. On the other hand, new-omics technologies are offering customized instruments and more and more advantageous results toward personalized medicine approaches, underlining the concept that each tumor mass undergoes a peculiar transformation process under the control of specific genes’ and proteins’ functional signatures. The main aim of this Special Issue was to collect novel contributions in the wide field of human tumor astrocytic basic and translational research, to suggest further potential therapeutic targets/strategies that might interfere, possibly at the earliest stage of transformation, with the tumor progression, and to increase the molecular-based arsenal to counteract the prognostic poverty of high-grade astrocytic tumors.