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Neuroblastoma is the most common extracranial solid tumour in the paediatric population. It is an embryonal tumour of the autonomic nervous system which arises in tissues of the sympathetic nervous system, typically in the adrenal medulla or paraspinal ganglia, and thus can present as mass lesions in the neck, chest, abdomen, or pelvis. The clinical presentation is highly variable. Mainly, the tumour is a mass that causes no symptoms; however, it can range from a primary tumour, a result of local invasion that causes critical illness, to a widely disseminated disease. The case is presented of a 6.5-monthold girl with hard, painless, purple-blue coloured subcutaneous nodules in the right and left subcostal area, which were the first manifestation of disseminated neuroblastoma 4S. The described case indicates that special oncological awareness should be maintained in every paediatric patient with undefined, non-characteristic skin lesions and subcutaneous nodules. [ABSTRACT FROM AUTHOR]

Purpose: Central nervous system (CNS) embryonal tumors are a diverse group of malignant tumors typically affecting pediatric patients that recently have been better defined, and this paper describes evolution of a unique type of embryonal tumor at relapse. Methods: Two pediatric patients with CNS embryonal tumors with EWSR1-PLAGL1 rearrangements treated at Arkansas Children's Hospital with histopathologic and molecular data are described. Results: These two patients at diagnosis were classified as CNS embryonal tumors with EWSR1-PLAGL1 rearrangements based on histologic appearance and molecular data. At relapse both patient's disease was reclassified as atypical teratoid rhabdoid tumor (ATRT) based on loss of INI-1, presence of SMARCB1 alterations, and methylation profiling results. Conclusion: CNS embryonal tumors with EWSR1-PLAGL1 rearrangements acquire or include a population of cells with SMARCB1 alterations that are the component that predominate at relapse, suggesting treatment aimed at this disease component at diagnosis should be considered. [ABSTRACT FROM AUTHOR]

Background: Small round cell tumors (SRCTs) are a group of malignant neoplasms with minimal or no differentiation, characterized by the presence of round cells with high nuclear-cytoplasmic ratio. Although SRCTs can occur in any part of the body, involvement of central nervous system (CNS) is uncommon. Aim: We aimed to study the clinicopathological spectrum of cranial SRCT diagnosed in our institute over a period of four years (2016-2019). Material and Methods: A retrospective review of medical records (2016-2019) with a morphological diagnosis of cranial SRCT was made. Both intra-axial and extra-axial tumors were included. A total of 60 cases were retrieved, and the clinical and histopathological features were studied. Special cytochemical staining and immunohistochemistry were performed, where needed. Results: The mean age at presentation was 18.4 years (range, 1-60 years), with a male-to-female ratio of 2.5:1. The most common site was posterior fossa of brain (n = 28, 47%), followed by dorso-lumbar spine (n = 9, 15%). The most common type of tumor was medulloblastoma (n = 29, 48.3%), followed by Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET) (n = 11, 18.3%), non-Hodgkin lymphoma (NHL) (n = 9, 15%), neuroblastoma (n = 3, 5%), and CNS embryonal tumor, NOS (n = 2, 3.3%). One case each of atypical teratoid rhabdoid tumor (ATRT), rhabdomyosarcoma, pineoblastoma, melanoma, rhabdomyosarcoma, and undifferentiated pleomorphic sarcoma was also documented. Conclusions: SRCTs have a variable age of presentation. Their incidence in CNS is low as compared to other organ systems. On light microscopy, the histopathology of these lesions is overlapping, posing a great diagnostic dilemma for the pathologist. The use of ancillary techniques like immunohistochemistry helps in arriving at the correct diagnosis. Treatment strategy and tumor prognosis also vary along the entire spectrum of SRCT, thus making exact characterization essential for proper management. [ABSTRACT FROM AUTHOR]

Beckwith-Wiedemann syndrome (BWS) is a rare and heterogeneous genetic condition characterized by overgrowth, organomegaly, and increased vulnerability to embryonal tumors. This review investigates the complex genetic and epigenetic pathways underlying Beckwith-Wiedemann syndrome, focusing on the 11p15.5 region on chromosome 11. Abnormalities in the 11p15.5 area, such as imprinting control region dysregulation and CDKN1C gene mutations, contribute to disrupted growth regulation. This content also provides an overview of the incidence and pathophysiology of this syndrome. Clinical manifestations include macrosomia, macroglossia, and abdominal wall abnormalities. The increased risk of embryonal malignancies, such as Wilms tumor and hepatoblastoma, emphasizes the importance of diligent medical observation. Early diagnosis through genetic testing is crucial for tailored management and genetic counseling. This detailed discussion of Beckwith-Wiedemann syndrome sheds light on the molecular complexities of the condition, emphasizing the significance of genetic testing, early detection, and multidisciplinary management for affected infants.

Huangliansu, also known as berberine, is abenzyl tetra isoquinoline alkaloid. Extracted from Coptis chinensis and other plants, it is also a major ingredient of Huanglian Jiedu Decoction, Zuojin Pills and other traditional Chinese medicine prescriptions. It has proved to have a variety of beneficial biological activities for treating infection, inflammation, cardiovascular diseases, gastrointestinal diseases, neurodegeneration, depression and metabolic disorders. Furthermore, it inhibits the proliferation and promotes apoptosis of esophageal cancer, colonic adenocarcinoma, liver cancer, osteosarcoma, breast cancer and other tumor cells through different mechanisms. Also it may act on a variety of cells of pediatric embryonal tumors, such as neuroblastoma, hepatoblastoma and rhabdomyosarcoma. Thus it is a potential antineoplastic drug. Through a literature review, the authors summarized the drug effects of berberine in embryonal tumors to provide references for follow-up studies. [ABSTRACT FROM AUTHOR]

Background: There are few assessments evaluating associations between birth defects with neural crest cell developmental origins (BDNCOs) and embryonal tumors, which are characterized by undifferentiated cells having a molecular profile similar to neural crest cells. The effect of BDNCOs on embryonal tumors was estimated to explore potential shared etiologic pathways and genetic origins. Methods: With the use of a multistate, registry‐linkage cohort study, BDNCO–embryonal tumor associations were evaluated by generating hazard ratios (HRs) and 95% confidence intervals (CIs) with Cox regression models. BDNCOs consisted of ear, face, and neck defects, Hirschsprung disease, and a selection of congenital heart defects. Embryonal tumors included neuroblastoma, nephroblastoma, and hepatoblastoma. Potential HR modification (HRM) was investigated by infant sex, maternal race/ethnicity, maternal age, and maternal education. Results: The risk of embryonal tumors among those with BDNCOs was 0.09% (co‐occurring n = 105) compared to 0.03% (95% CI, 0.03%–0.04%) among those without a birth defect. Children with BDNCOs were 4.2 times (95% CI, 3.5–5.1 times) as likely to be diagnosed with an embryonal tumor compared to children born without a birth defect. BDNCOs were strongly associated with hepatoblastoma (HR, 16.1; 95% CI, 11.3–22.9), and the HRs for neuroblastoma (3.1; 95% CI, 2.3–4.2) and nephroblastoma (2.9; 95% CI, 1.9–4.4) were elevated. There was no notable HRM by the aforementioned factors. Conclusions: Children with BDNCOs are more likely to develop embryonal tumors compared to children without a birth defect. Disruptions of shared developmental pathways may contribute to both phenotypes, which could inform future genomic assessments and cancer surveillance strategies of these conditions. Associations between nonchromosomal birth defects of neural crest cell developmental origins and pediatric embryonal tumors were investigated based on potential shared developmental pathways. With the use of data from a multistate, registry‐linkage cohort study, children born with these birth defects were found to be more likely (hazard ratio, 4.2; 95% CI, 3.5–5.1) to be diagnosed with the selected embryonal tumors than children without a birth defect, especially hepatoblastoma (hazard ratio, 16.1; 95% CI, 11.3–22.9). [ABSTRACT FROM AUTHOR]

Nowadays the development of technology in all spheres of science results in expanded and precise diagnostic possibilities in pediatric neurology. The holistic progression leads to establishing an exact diagnosis from the wide spectrum of differential diagnoses presented with symptoms which are not pathognomonic. As it is previously well elaborated in the literature, epilepsies are a broad diagnostic term and only a small proportion of them belong to ocular myoclonus, especially when symptomatic. Materials and methods: We present a case report of a 18-month-old female child presenting several daily unilateral eyelid myoclia followed by shortlasting selflimiting atonic seizures. After excluding ophthalmological causes, detailed neurologic physical examination and electroencephalography were performed. Due to inconclusiveness, imaging diagnostic procedures (CTm,MRim) were also performed. Case report: The first neurological examination takes place at the age of 16 months, with a heteroanamnesis of occasional drooping of the left eyelid, which returns to its normal state spontaneously. On several occasions the previous event is followed with vomiting and a short attention deficit episode. The neurological examination in that particular moment was unremarkable and laboratory findings showed no abnormalities. Electroencephalographic recordings showed epileptogenic activity in the occipital lobe and raised the question of differential diagnosis, considering Panayiotopoulos Syndrome- benign early onset epilepsy. It was continued with further imaging diagnostics - MRIm that revealed the existence of a solid tumor mass with a diameter of 35-40 mm that compresses the pons, mesencephalon, parahippocampal lobe and hippocampus and also involves the basilar artery. The lesion had a suprasellar extension, but no affection of the optic chiasm was visualized. Results and therapy: The patient underwent neurosurgical extirpation of the tumor and pathohistological tissue examination and grading and molecular diagnostic. Embryonal tumor with multilayered rosettes (ETMR), C19MC-altered (WHO grade IV) was the final diagnosis. This embryonal tumour is identified by amplification on the C19MC region on chromosome 19 (19q13. 42). It tends to be diagnosed primarily in children under 4 years old, but is so rare that no incidence statistics are available. Conclusion: In the pediatric neurology department, even subtle neurologic symptoms deserve extensive attention. The challenge in diagnostics is to make a differentiation from the need for extensive and expensive diagnostics when we previously have a high probability direction that indicates a benign condition. The dilemma will always remain open considering the rare situations that may not merit protocol, but they turned out to be life-saving. [ABSTRACT FROM AUTHOR]

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Background: Embryonal tumors are highly malignant cancers of the central nervous system, with a relatively high incidence in infants and young children. Even with intensive multimodal treatment, the prognosis of many types is guarded, and treatment-related toxicity is significant. Recent advances in molecular diagnostics allowed the discovery of novel entities and inter-tumor subgroups, with opportunities for improved risk-stratification and treatment approaches. Summary: Medulloblastomas separate into four distinct subgroups with distinct clinicopathologic characteristics, and data from recent clinical trials for newly diagnosed medulloblastoma support subgroup-specific treatment approaches. Atypical teratoid rhabdoid tumor (ATRT), embryonal tumor with multilayered rosettes (ETMR), and pineoblastoma, as well as other rare embryonal tumors, can be distinguished from histologically similar tumors by virtue of characteristic molecular findings, with DNA methylation analysis providing a strong adjunct in indeterminate cases. Methylation analysis can also allow further subgrouping of ATRT and pineoblastoma. Despite the dire need to improve outcomes for patients with these tumors, their rarity and lack of actionable targets lead to a paucity of clinical trials and novel therapeutics. Key Messages: (1) Embryonal tumors can be accurately diagnosed with pediatric-specific sequencing techniques. (2) Medulloblastoma risk stratification and treatment decisions should take into account molecular subgroups. (3) There is a dire need for a novel collaborative clinical trial design to improve outcomes is rare pediatric embryonal tumors. [ABSTRACT FROM AUTHOR]

Introduction/Background: Central nervous system (CNS) tumors in infants are rare, ranging between 1 and 10% of all pediatric CNS tumors. The infratentorial location is a challenge to neuro-oncologist and -surgeons due their subtle clinical presentation, different histopathological types, biological behaviors, and anesthetic-surgery difficulties. Methods: Single center retrospective study of infants diagnosed with posterior fossa tumors between 2010 and 2023. Results: Nineteen patients were included. Mean age 8.8 months; eight males. The most common presenting symptom was torticollis (n-6, 31.6%), followed by vomiting (n-3, 15.8%) and increased head circumference (n-3, 15.8%). Atypical Teratoid Rhabdoid Tumor (AT/RT) was the most common subtype (n-11, 57.9%), followed by Medulloblastoma (MB). Metastatic disease at diagnosis was evident in five cases. Seventeen patients initially underwent correction of hydrocephalus. Regarding surgical resection, one (5.3%) patient underwent biopsy, 13 (68.4%) complete resection, four (21%) partial resection. Only one patient, diagnosed with ependymoma, did not receive chemotherapy after surgery, 14/19 received highdose chemotherapy, eight of these followed by autologous bone marrow transplantation (ABMT). Focal radiotherapy (RT) was performed in four patients with AT/RT and in one ependymoma, following ABMT and complete resection, respectively. Event-free survival at 2 and 5 years was 64.9% and overall survival 63.2% and 54.2% respectively. Conclusion: Despite aggressive histological subtypes, neurosurgical challenges, and limitation of adjuvant therapy, we have shown acceptable survival rates in this challenging group of patients showing the importance of appropriate supportive care, improvement in surgical techniques and a multi-professional approach. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells exhibit unrestrained cell growth and proliferation owing to tumor-specific characteristics such as altered metabolism. Tumor cells vary metabolic pathways to meet their needs for rapid cell growth. In this review, we focus particularly on lipid metabolism in embryonal tumors with deregulated MYCN function, specifically neuroblastoma, retinoblastoma, Wilms tumor, medulloblastoma, and rhabdomyosarcoma. We also discuss whether we can target lipid metabolism to restrict tumor cell growth and proliferation. Tumor cells reprogram their metabolism, including glucose, glutamine, nucleotide, lipid, and amino acids to meet their enhanced energy demands, redox balance, and requirement of biosynthetic substrates for uncontrolled cell proliferation. Altered lipid metabolism in cancer provides lipids for rapid membrane biogenesis, generates the energy required for unrestricted cell proliferation, and some of the lipids act as signaling pathway mediators. In this review, we focus on the role of lipid metabolism in embryonal neoplasms with MYCN dysregulation. We specifically review lipid metabolic reactions in neuroblastoma, retinoblastoma, medulloblastoma, Wilms tumor, and rhabdomyosarcoma and the possibility of targeting lipid metabolism. Additionally, the regulation of lipid metabolism by the MYCN oncogene is discussed. [ABSTRACT FROM AUTHOR]

Introduction/Background: Central nervous system (CNS) tumors in infants are rare, ranging between 1 and 10% of all pediatric CNS tumors. The infratentorial location is a challenge to neuro-oncologist and -surgeons due their subtle clinical presentation, different histopathological types, biological behaviors, and anesthetic-surgery difficulties. Methods: Single center retrospective study of infants diagnosed with posterior fossa tumors between 2010 and 2023. Results: Nineteen patients were included. Mean age 8.8 months; eight males. The most common presenting symptom was torticollis (n-6, 31.6%), followed by vomiting (n-3, 15.8%) and increased head circumference (n-3, 15.8%). Atypical Teratoid Rhabdoid Tumor (AT/RT) was the most common subtype (n-11, 57.9%), followed by Medulloblastoma (MB). Metastatic disease at diagnosis was evident in five cases. Seventeen patients initially underwent correction of hydrocephalus. Regarding surgical resection, one (5.3%) patient underwent biopsy, 13 (68.4%) complete resection, four (21%) partial resection. Only one patient, diagnosed with ependymoma, did not receive chemotherapy after surgery, 14/19 received high-dose chemotherapy, eight of these followed by autologous bone marrow transplantation (ABMT). Focal radiotherapy (RT) was performed in four patients with AT/RT and in one ependymoma, following ABMT and complete resection, respectively. Event-free survival at 2 and 5 years was 64.9% and overall survival 63.2% and 54.2% respectively. Conclusion: Despite aggressive histological subtypes, neurosurgical challenges, and limitation of adjuvant therapy, we have shown acceptable survival rates in this challenging group of patients showing the importance of appropriate supportive care, improvement in surgical techniques and a multi-professional approach.

New groups of high-grade neuroepithelial tumours (HGNET) have emerged from the reclassification of central nervous system (CNS) embryonal tumours that have recognised CNS HGNET with BCOR alteration (CNS HGNET-BCOR). We report a two-year, nine-month-old Omani boy who presented to the Royal Hospital, Muscat, Oman, in 2015 with subacute head tilting and neck pain. A well-defined cerebellar lesion was found and he was treated with standard chemoradiotherapy. After a relapse at the age of five years, molecular testing revealed a BCOR alteration. He was treated with further surgery and high-dose chemotherapy; unfortunately, he relapsed and died three years after he was diagnosed.

Simple Summary: Lateralized overgrowth may be isolated or accompany syndromes. Recently, international BWS consensus proposed that the patients with isolated lateralized overgrowth and epigenetic change related to this syndrome should be evaluated within the Beckwith–Wiedemann spectrum. The risk of cancer is high in patients with lateralized overgrowth, some patients also may be admitted presenting with a tumor. The aim of this study was to classify patients with lateralized overgrowth into isolated, atypical, and classic phenotypes according to consensus scoring, to investigate epigenetic alterations on chromosome 11p15.5, and to raise awareness for early detection and prevention of cancer. The Beckwith–Wiedemann spectrum (BWSp) ranges from isolated lateralized overgrowth (ILO) to classic phenotypes. In this broad clinical spectrum, an epigenetic alteration on chromosome 11p15.5 can be detected. The risk for embryonal tumors is high, especially in patients with lateralized overgrowth (LO). The aim of this study is to investigate epigenetic alterations in 11p15.5 and tumor risk in 87 children with LO. The methylation level of 11p15.5 was examined in the blood of all patients and in skin samples or buccal swabs from 40 patients with negative blood tests; 63.2% of patients were compatible with the ILO phenotype, 18.4% were atypical, and 18.4% were classic. The molecular diagnosis rate was 81.2% for the atypical and classic phenotypes, and 10.9% for the ILO phenotype. In patients with epigenetic alterations, LO was statistically significantly more severe than in test negatives. Tumors developed in six (6.9%) of the total 87 patients with LO; four belonged to the atypical or classical phenotype (12.5%) and two to ILO (3.5%). Three of the four patients with atypical/classical phenotypes had pUPD11, one had IC1-GOM alteration, and two ILO patients were negative. We conclude that LO patients should be monitored for tumor risk even if their epigenetic tests are negative. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals treated for brain tumors in childhood are at high risk of cognitive and other late complications. The aim of this nationwide registry study was to explore further education following the nine years of compulsory school in Sweden in teenagers and young adults treated for childhood brain tumors. Individuals treated for embryonal tumors, low grade astrocytomas, optic pathway gliomas, craniopharyngiomas, and neuronal and mixed neuronal–glial tumors, were analyzed separately. All individuals treated for brain tumors were compared to about five times as many matched controls without cancer diagnoses or treatments. Our results demonstrate significant differences between cases and controls regarding attendance in high school, folk high school, and university. Individuals treated for embryonal tumors or optic pathway gliomas attended post-compulsory education less frequently than other analyzed diagnoses. There was a positive correlation between parental education levels and attendance in high school and university for both cases and controls. The risk of late complications after a brain tumor in childhood is high. Both the tumor itself and the treatments give rise to sequelae that affect daily life activities. In this registry study, we explored post-compulsory education, i.e., further education following the nine compulsory years in school, in 452 cases born 1988–1996 and diagnosed with a brain tumor before their fifteenth birthday. They were compared with 2188 individual controls who were not treated for cancer. Significantly fewer teenagers and young adults treated for brain tumors in childhood attended high school or university compared with controls, especially individuals treated for embryonal tumors or optic pathway gliomas. A significantly larger proportion of subjects treated for embryonal tumors and craniopharyngiomas attended folk high schools, a type of post-compulsory school with a more accessible learning environment. For both cases and controls, we observed a positive correlation between parental education levels and attendance in high school and university. In our previous studies we have shown that children treated for brain tumors, as a group, tend to perform worse during their last year of compulsory school compared with their peers, and the current study confirms that these differences remain over time. [ABSTRACT FROM AUTHOR]

Introduction: 177Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A. Methods: SST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by an experienced pathologist (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (<10%), 2 (10-50%), 3 (51-80%), or 4 (>80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (Range: 0-12). Results: A total of 120 tumor samples from 114 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean ± SD: 7.5 ± 3.6 [n=38]) and meningioma (5.7 ± 3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3 ± 0.6 [n=3]), ETMR (1.0 ± 0 [n=3]), ependymoma (grades I-III; 0.2 ± 0.7 [n=27]), and high-grade glioma (grades IIIIV; 0.4 ± 0.7 [n=23]). Pineoblastoma (3.8 ± 1.5 [n=4]) and other embryonal tumors (2.0 ± 4.0 [n=7]) exhibited intermediate, variable expression. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.5 ± 3.1) than SHH (5.0 ± 3.3) molecular subgroups (p=0.033). In a subset of paired primary and recurrent specimens from four patients, SST2A IHC scores remained largely unchanged. Discussion: High membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors. [ABSTRACT FROM AUTHOR]

This study evaluates the diagnostic utility of OLIG2 immunohistochemistry for distinguishing between pediatric high-grade gliomas (pHGG) and embryonal tumors (ETs) of the CNS. Utilizing a retrospective pediatric cohort (1990-2021) of 56 CNS tumors, classified initially as primitive neuroectodermal tumors or CNS ET, we reclassified the cases based on WHO CNS5 criteria after comprehensive review and additional molecular testing that included next-generation sequencing and DNA methylation profiling. Our results indicate that OLIG2 immunopositivity was negative or minimal in a significant subset of pHGG cases (6 out of 11). At the same time, it showed diffuse expression in all cases of CNS neuroblastomas with FOXR2 activation (5/5), demonstrating its limited specificity in differentiating between pHGG and ET. Variable OLIG2 expression in other ETs, ATRT, and ETMR suggests the broader diagnostic implications of the marker. Furthermore, incidental findings of OLIG2 positivity in cases traditionally expected to be negative, such as medulloblastoma and ependymoma, introduce an additional layer of complexity. Together, these findings highlight the challenges of relying solely on OLIG2 immunostaining for accurate tumor classification in pediatric CNS neoplasms and underscore the importance of an integrated diagnostic approach., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Abstract Background Brain tumors in the first years of life are frequently encountered recently with the advancement in neuroimaging, neurosurgery and neuroanethesia where early diagnosis of these lesions became available even before birth. Their management is challenging where the surgery is technically demanding, radiotherapy is omitted in this age because of its late sequelae and chemotherapy role may be beneficial, but it is limited also by its side effects and neurotoxicity. The aim of this article is to review the current literature about the brain tumors in the first two years of life, their diagnosis and treatment. Main body Brain tumors in the first two years of life encompass mainly fetal/congenital tumors and infantile tumors. They account for 1.4–18% of cases of pediatric brain tumor, and most of them are diagnosed in the first year of life. The main histopathologies diagnosed are glial tumors, choroid plexus tumors, medulloblastoma and other embryonal tumors, teratoma and ependymoma. They are mainly supratentorial. Large head and bulging fontanelles are the main presenting symptoms and signs secondary to increased intracranial pressure secondary to large tumors or associated hydrocephalus. Prenatal and postnatal ultrasonography represents the initial imaging step in the diagnosis that should be complemented by MRI and CT brain. The main and first line of treatment of infantile brain tumors is surgical excision as the prognosis is directly related to the extent of resection besides surgery offers specimens for histopathological diagnosis and adjuvant chemotherapy is given for residual irresectable cases and malignant tumors with the main aim to delay radiotherapy beyond the age of three years. Conclusion Brain tumors in the first two years of life are a challenging group of different histopathological entities with underlying specific molecular characterization and genetic predispositions. They have aggressive behavior and general poor prognosis with limited options of management. Individualized multidisciplinary management for each case is needed, and future studies for therapeutic medications targeting underlying molecular biology may improve their outcome.

Introduction177Lu-DOTATATE, a radionuclide therapy that binds somatostatin type-2A receptors (SST2A), has demonstrated efficacy in neuroendocrine tumors and evidence of central nervous system (CNS) penetration, supporting potential expansion within pediatric neuro-oncology. Understanding the prevalence of SST2A expression across pediatric CNS tumors is essential to identify patients who may benefit from somatostatin receptor-targeted therapy and to further elucidate the oncogenic role of SST2A.MethodsSST2A immunohistochemistry (IHC) was performed on tumor specimens and interpreted by an experienced pathologist (blinded), utilizing semi-quantitative scoring of membranous expression within viable tumor. Immunoreactive cell percentage was visually scored as 0 (none), 1 (80%). Staining intensity was scored as 0 (none), 1 (weak), 2 (moderate), or 3 (strong). Combined scores for each specimen were calculated by multiplying percent immunoreactivity and staining intensity values (Range: 0-12).ResultsA total of 120 tumor samples from 114 patients were analyzed. Significant differences in SST2A IHC scores were observed across histopathologic diagnoses, with consistently high scores in medulloblastoma (mean ± SD: 7.5 ± 3.6 [n=38]) and meningioma (5.7 ± 3.4 [n=15]), compared to minimal or absent expression in ATRT (0.3 ± 0.6 [n=3]), ETMR (1.0 ± 0 [n=3]), ependymoma (grades I-III; 0.2 ± 0.7 [n=27]), and high-grade glioma (grades III-IV; 0.4 ± 0.7 [n=23]). Pineoblastoma (3.8 ± 1.5 [n=4]) and other embryonal tumors (2.0 ± 4.0 [n=7]) exhibited intermediate, variable expression. Among medulloblastomas, SST2A IHC scores were higher in non-SHH (8.5 ± 3.1) than SHH (5.0 ± 3.3) molecular subgroups (p=0.033). In a subset of paired primary and recurrent specimens from four patients, SST2A IHC scores remained largely unchanged.DiscussionHigh membranous SST2A expression was demonstrated in medulloblastoma, meningioma, and some rarer embryonal tumors with potential diagnostic, biologic, and therapeutic implications. Somatostatin receptor-targeted therapy such as 177Lu-DOTATATE deserves further investigation in these highly SST2A-expressing pediatric CNS tumors.

Introduction. Medulloblastomas are embryonic tumors that arise exclusively in the posterior fossa and have the potential for leptomeningeal spread. Due to the aggressive nature of the tumor and age-related features of the posterior cranial fossa in children, treatment with medulloblastoma is associated with significant complications and high mortality. The purpose of our study was to evaluate the results of surgical treatment of children with medulloblastoma treated in our center. Materials and methods. The study included the outcomes of surgical treatment of 71 patients with a verified diagnosis of “Medulloblastoma” who underwent surgical treatment on the basis of JSC “National Centre for Neurosurgery” from 2015 to 2020. Results. The average age of patients was 6.1 ± 3.3 years (1 month – 16 years). In most cases, the clinical features were presented by hypertension-hydrocephalus syndrome (94.36%). The mortality rate within 1 year was 15.49%. The number of deaths in patients with desmoplastic/nodular medulloblastomas was lower (7.31%) than in children with large-cell/anaplastic medulloblastoma (50%). Total tumor resection was associated with lower mortality (5.26%) than partial removal (15.78%). Conclusion. With a maximally safe resection and following chemoradiotherapy, the prognosis of medulloblastoma is favorable. However, improvements are required in stratifying the risk of medulloblastoma and profiling individual therapy for each child based on the molecular type in order to increase survival rates and decrease relapses. [ABSTRACT FROM AUTHOR]

Simple Summary: Embryonal tumors include a heterogeneous group of tumors that need multimodal and multidisciplinary treatments in which craniospinal irradiation (CSI) plays a major role, with a known impact on the acute toxicity and future quality of life of patients. Neutropenia represents one of the most common acute hematological side effects and is responsible for infections and treatment delays that can affect the effectiveness of therapy. To better describe hematological acute toxicity during proton beam radiation treatment, we retrospectively examined 20 subsequent pediatric patients affected by high-risk embryonal tumors subjected to CSI with dual-phase proton therapy after a chemotherapy regimen. Our data suggest that the dual-phase technique is safe and feasible in this setting of pediatric patients with a significant baseline hematological toxicity. Despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with proton therapy, and, therefore, no treatment was discontinued or delayed. Background: Embryonal tumors represent a heterogeneous entity of brain tumors that need a multidisciplinary treatment including cranio-spinal irradiation (CSI), with a known impact on the acute toxicity. Proton therapy (PT) boasts a reduction in acute hematological toxicity. Methods: We retrospectively examined 20 pediatric patients affected by high-risk medulloblastoma and other rare embryonal brain tumors subjected to CSI with PT from September 2016 to April 2020. Before CSI, all patients received induction chemotherapy, and three patients additionally received two high-dose courses with thiotepa, followed by an autologous haemopoietic stem cell transplantation. We recorded the total white blood cell count, absolute neutrophil count, platelets, and hemoglobin levels for all patients during PT. Results: Leucocytes and neutrophils decreased directly after the beginning of treatment, reaching a complete recovery at the end of treatment. Hemoglobin values remained constant over the treatment course. The median platelet value decreased until reaching a plateau around halfway through therapy, followed by a slow increase. No cases of febrile neutropenia or severe infections were reported. No treatment discontinuation due to hematological toxicity was necessary. Conclusions: CSI with PT was proven to be safe in this setting of pediatric patients. Our study showed that despite all patients having undergone chemotherapy prior to irradiation, no serious hematological toxicity was reported at the end of the treatment with PT, and, therefore, no treatment was discontinued or delayed. [ABSTRACT FROM AUTHOR]

Primary brain tumors are the most common solid neoplasms in children and a leading cause of mortality in this population. MRI plays a central role in the diagnosis, characterization, treatment planning, and disease surveillance of intracranial tumors. The purpose of this review is to provide an overview of imaging methodology, including conventional and advanced MRI techniques, and illustrate the MRI appearances of common pediatric brain tumors. [ABSTRACT FROM AUTHOR]

Background Occurrences of suprasellar central nervous system (CNS) embryonal tumors in adults are extremely rare. Hemorrhagic onset is further uncommon, with only anecdotic cases reported in the literature. The authors describe the case of a 57-year-old man affected by a suprasellar CNS embryonal tumor, with hemorrhagic onset and a unique diffusion pattern along the optic pathways. Material and Methods A 57-year-old man presenting with acute visual acuity worsening and left homonymous hemianopia was referred to our hospital. Neuroradiologic studies demonstrated an infiltrating, high-grade lesion involving the optic chiasm and right retrochiasmatic pathways with a hemorrhagic area in the ipsilateral pulvinar. Results The patient underwent microsurgical biopsy. Pathologic assessment confirmed the diagnosis of CNS embryonal tumor, not otherwise specified (NOS) according to the 2016 World Health Organization (WHO) classification of CNS tumors. The patient was referred to a multimodal adjuvant treatment; he eventually died 4 months after surgery. Competent literature has been systematically reviewed in the light of the relevant changes made in the last version of the WHO classification. Conclusion Embryonal tumors should be considered in the differential diagnosis for sellar and suprasellar space-occupying lesions, despite the rarity of the disease and the uncommon features at time of presentation. As per our knowledge, this is the first case ever described of hemorrhagic suprasellar embryonal tumor with a diffusion pattern along white matter fibers. Histogenesis, biomolecular and neuroradiologic features, and classification of embryonal tumors are an open field of research, with considerable implications for the definition of better diagnostic pitfalls and therapeutic regimens. [ABSTRACT FROM AUTHOR]

Background: Pediatric malignancies are one of the most common causes of childhood morbidity and mortality. The prevalence of different malignancies in the pediatric age group varies from one place to another. The present study was done to find out the occurrence of childhood malignancies in the southern region of West Bengal to compare the patterns of different malignancies with other established epidemiological studies and to search for the specific causes for apparently increased occurrence of childhood malignancies. Methods: A prospective study was conducted for 7 years in which patients with pediatric malignancies were included in the study. The clinicopathological features of each case were analyzed. Results: A total number of 247 cases were included in the study among which 162 were males (65.59%). Children below the age of 5 years accounted for 90 cases (36.58%). Hematological malignancies were found in 122 cases (49.39%), and the rest constituted nonhematological malignancies (125, 50.61%). The most common malignant disorder noted was acute leukemia, constituting about 33.37% of cases (82 cases). The highest occurrence (37.9%) of malignancies was encountered in 5–10 years of age, and the next common (31.7%) was between the age group of 2 and 5 years. The most common malignancies noted in these age groups were acute leukemia, retinoblastoma, Wilm's tumor, and neuroblastoma. Conclusion: Lympho-hematogeneous malignancies were the most common followed by embryonal tumors. Although the occurrence of hematological malignancies was comparable to the similar studies of the developed countries, the corresponding figures of central nervous system tumors were considerably less.

Background: Liquid biopsy assays that detect cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) are a promising tool for disease monitoring in pediatric patients with primary central nervous system (CNS) tumors. As a compliment to tissue-derived molecular analyses, CSF liquid biopsy has the potential to transform risk stratification, prognostication, and precision medicine approaches., Methods: In this pilot study, we evaluated a clinical pipeline to determine feasibility and sensitivity of low-pass whole genome sequencing (LP-WGS) of CSF-derived cfDNA from patients with CNS embryonal tumors. Thirty-two longitudinal CSF samples collected from 17 patients with molecularly characterized medulloblastoma (12), embryonal tumor with multilayered rosettes (2), CNS embryonal tumor, not elsewhere classified (NEC) (2), and atypical teratoid/rhabdoid tumor (1) were analyzed., Results: Adequate CSF-derived cfDNA for LP-WGS analysis was obtained in 94% of samples (30/32). Copy number variants compatible with neoplasia were detected in 90% (27/30) and included key alterations, such as isodicentric ch17, monosomy 6, and MYCN amplification, among others. Compared to tissue specimens, LP-WGS detected additional aberrations in CSF not previously identified in corresponding primary tumor specimens, suggesting a more comprehensive profile of tumor heterogeneity or evolution of cfDNA profiles over time. Among the 12 CSF samples obtained at initial staging, only 2 (17%) were cytologically positive, compared to 11 (92%) that were copy number positive by LP-WGS., Conclusions: LP-WGS of CSF-derived cfDNA is feasible using a clinical platform, with greater sensitivity for tumor detection compared to conventional CSF cytologic analysis at initial staging. Large prospective studies are needed to further evaluate LP-WGS as a predictive biomarker., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Background: Brain tumors in the first years of life are frequently encountered recently with the advancement in neuroimaging, neurosurgery and neuroanethesia where early diagnosis of these lesions became available even before birth. Their management is challenging where the surgery is technically demanding, radiotherapy is omitted in this age because of its late sequelae and chemotherapy role may be beneficial, but it is limited also by its side effects and neurotoxicity. The aim of this article is to review the current literature about the brain tumors in the first two years of life, their diagnosis and treatment. Main body: Brain tumors in the first two years of life encompass mainly fetal/congenital tumors and infantile tumors. They account for 1.4–18% of cases of pediatric brain tumor, and most of them are diagnosed in the first year of life. The main histopathologies diagnosed are glial tumors, choroid plexus tumors, medulloblastoma and other embryonal tumors, teratoma and ependymoma. They are mainly supratentorial. Large head and bulging fontanelles are the main presenting symptoms and signs secondary to increased intracranial pressure secondary to large tumors or associated hydrocephalus. Prenatal and postnatal ultrasonography represents the initial imaging step in the diagnosis that should be complemented by MRI and CT brain. The main and first line of treatment of infantile brain tumors is surgical excision as the prognosis is directly related to the extent of resection besides surgery offers specimens for histopathological diagnosis and adjuvant chemotherapy is given for residual irresectable cases and malignant tumors with the main aim to delay radiotherapy beyond the age of three years. Conclusion: Brain tumors in the first two years of life are a challenging group of different histopathological entities with underlying specific molecular characterization and genetic predispositions. They have aggressive behavior and general poor prognosis with limited options of management. Individualized multidisciplinary management for each case is needed, and future studies for therapeutic medications targeting underlying molecular biology may improve their outcome. [ABSTRACT FROM AUTHOR]

Beckwith-Wiedemann Syndrome (BWS) is a rare genetic disorder characterized by overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycemia, predisposition to embryonal tumor, lateralized overgrowth, and leg length discrepancy (LLD), which can affect normal posture and gait. Aim of this study was to evaluate the effects of guided growth (temporary epiphysiodesis technique) as LLD management in BWS patients. Between 2007 and 2021, 22 BWS patients (15 F, 7 M) with a mean age of 7.9 years (2.9–14.4) and a mean LLD at first surgery of 3.65 cm (2–10), underwent temporary proximal tibial (PTE) and distal femur epiphysiodesis (DFE). In 18 patients the first surgical procedure was PTE, in one, DFE, and in 3 cases, PTE and DFE at the same time, respectively. Eleven patients reached equality of leg length after a mean follow-up of 7.7 years (3.7–13.0) and mean age of 13.3 years (12.7–27.5); 10 patients underwent 3 surgical procedures, one 7 procedures. Fifteen patients had no complications. No severe complications, infection, articular stiffness, or neuro-vascular lesions occurred in remaining patients; complications included secondary varus or valgus axial deviation in a total of 6 patients, and two screw breakages in two patients. Guided growth as a minimally invasive procedure seems efficient for LLD treatment with low complication rate in BWS patients. [ABSTRACT FROM AUTHOR]

Background: Germinoma is a rare lesion found commonly in the pineal and suprasellar regions of the brain. Clinical presentation mainly involves the location and size of the tumor and the patient age. Endocrine abnormalities are the most common symptom. Case presentation: The patient was a 26-year-old Iranian female who suffered from germinoma for a long time and was referred to Loghman Hakim Hospital for amenorrhea, polyuria, and polydipsia. Despite diagnostic challenges, she was finally diagnosed with suprasellar germinoma after endoscopic transsphenoidal surgery, followed by radiotherapy and medical interventions to complement the surgery. Conclusion: It is important to be able to diagnose the patient's problem at an early stage based on their history, hormonal profile, laboratory results and radiological view. [ABSTRACT FROM AUTHOR]

Beckwith‐Wiedemann syndrome (BWS) is a genomic imprinting disorder, characterized by macroglossia, abdominal wall defects, lateralized overgrowth, and predisposition to embryonal tumors. It is caused by the defect of imprinted genes on chromosome 11p15.5, regulated by imprinting control (IC) domains, IC1, and IC2. Rarely, CDKN1C and chromosomal changes can be detected. The aim of this study is to retrospectively evaluate 55 patients with BWS using the new diagnostic criteria developed by the BWS consensus, and to investigate (epi)genetic changes and follow‐up findings in classic and atypical phenotypes. Loss of methylation in IC2 region (IC2‐LoM), 11p15.5 paternal uniparental disomy (pUPD11), and methylation gain in IC1 region (IC1‐GoM) are detected in 31, eight, and five patients, respectively. Eleven patients have had no molecular defects. Thirty‐five patients are classified as classical and 20 as atypical phenotype. Patients with classical phenotype are more frequent in the IC2‐LoM (25/31), while patients with atypical phenotype are common in the pUPD11 group (5/8). Malignant tumors have developed in six patients (10.9%); three of these patients have IC1‐GoM, two pUPD11, one IC2‐LoM genotype, and four an atypical phenotype. We observed that the face was round in the infantile period and elongated as the child grew‐up, developing prognathism and becoming asymmetrical if hemi‐macroglossia was present in the classical phenotype. These findings were mild in the atypical phenotype. These results support the importance of using the new diagnostic criteria to facilitate the diagnosis of patients with atypical phenotype who have higher tumors risk. This study also provides important information about facial gestalt. [ABSTRACT FROM AUTHOR]

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Background/Aim: Proteus syndrome is a sporadic disease that is particularly noticeable due to the disproportional growth of body segments. The disease is a genetic mosaic. The mutations can arise from any of the germ layers, an explanation of the very variable phenotype. The aim of this report is to communicate the diagnosis and management of an unusual case of Proteus Syndrome with special attention to oral and craniofacial findings. Case Report: A 15-year-old patient was referred for surgical treatment of pronounced skull malformations and correction of oral mucosal hyperplasia. Treatment caused significant improvement in facial appearance and oral soft tissue conditions. Conclusion: Surgical measures adapted to the local findings and symptoms can often relieve severe disfigurement of the patient. [ABSTRACT FROM AUTHOR]

A subset of pediatric tumors affects very young children and are thought to arise during fetal life. A common theme is that these embryonal tumors hijack developmental programs, causing a block in differentiation and, as a consequence, unrestricted proliferation. Embryonal tumors, therefore typically maintain an embryonic gene signature not found in their differentiated progeny. Still, the processes underpinning malignant transformation remain largely unknown, which is hampering therapeutic innovation. To gain more insight into these processes, in vitro and in vivo research models are indispensable. However, embryonic development is an extremely dynamic process with continuously changing cellular identities, making it challenging to define cells-of-origin. This is crucial for the development of representative models, as targeting the wrong cell or targeting a cell within an incorrect developmental time window can result in completely different phenotypes. Recent innovations in in vitro cell models may provide more versatile platforms to study embryonal tumors in a scalable manner. In this review, we outline different in vitro models that can be explored to study embryonal tumorigenesis and for therapy development.

Primary brain tumors are the most common solid neoplasms in children and a leading cause of mortality in this population. MRI plays a central role in the diagnosis, characterization, treatment planning, and disease surveillance of intracranial tumors. The purpose of this review is to provide an overview of imaging methodology, including conventional and advanced MRI techniques, and illustrate the MRI appearances of common pediatric brain tumors.

Copyright of Orvosképzés is the property of Semmelweis Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Though the central nervous system tumor comprises ~2% of all the tumors, an overall increase has been observed especially in less developed countries. This increase in the incidence may be due to exposure of population to various risk factors or improved diagnosis with advancement in the ancillary studies. This study aims to provide a single centre histopathological spectrum of this type of tumor.Materials and Methods: A retrospective cross sectional study on a series of cases was performed in the Department of Pathology, Annapurna Neurological Institute & Allied Science , Maitighar , Kathmandu, Nepal from April 2013 to Jan 2016. Data were analyzed using SPSS version 21.0.Results: A total of 221 brain and CNS tumors (125 females and 96 males) were studied. The mean age at diagnosis was 43.77 years. The most common tumor was meningioma(67 cases, 30.3%), followed by astrocytic tumor (57 cases, 25.7%) and pituitary adenoma(30 cases,13.6%). The frequency of WHO grade I, II,III and IV tumor were 94 cases (55%), 34 cases (19.9%),10 cases (5.8%), and 33 cases (19.3%) respectively. The astrocytic tumor was most frequent tumor in children (7/20 caes, 37 %).Conclusion: This study showed the most common CNS tumor to be meningioma followed by astrocytic tumors and pituitary adenoma. The spectrum of CNS tumor in children showed divergent histologic pattern according to the age. In age group 0-10 years embryonal tumors were common whereas ages group of 12-years showed propensity towards astrocytoma as in adults.

Introduction: ETMRs are highly lethal, pediatric embryonal brain tumors, previously classified as various histologic diagnoses including supratentorial primitive neuroectodermal tumors (sPNET) and CNS PNET. With recognition that these tumors harbor recurrent amplification of a novel oncogenic miRNA cluster on chr19, C19MC, ETMRs were designated as a distinct biological and molecular entity with a spectrum of histologic and clinical manifestations. Methods: We reviewed published literature describing clinical presentation, the genetic and epigenetic drivers of oncogenesis, and recent therapeutic strategies adopted to combat these aggressive tumors. Results: As a consequence of C19MC amplification, ETMRs upregulate several oncogenic and pluripotency proteins, including LIN28A, DNMT3B and MYCN, that confer a unique epigenetic signature reminiscent of nascent embryonic stem cells. In this review, we focus on the dysregulation of miRNAs in ETMR, the major pathogenic mechanism identified in this disease. Conclusion: Despite the use of multi-modal therapeutic regimens, ETMR patients have dismal survival. Understanding the unique biology of these tumors has provided new insights towards novel therapeutic targets. [ABSTRACT FROM AUTHOR]