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Ependymoma is a tumor of the brain or spinal cord. The two most common and aggressive molecular groups of ependymoma are the supratentorial ZFTA-fusion associated and the posterior fossa ependymoma group A. In both groups, tumors occur mainly in young children and frequently recur after treatment. Although molecular mechanisms underlying these diseases have recently been uncovered, they remain difficult to target and innovative therapeutic approaches are urgently needed. Here, we use genome-wide chromosome conformation capture (Hi-C), complemented with CTCF and H3K27ac ChIP-seq, as well as gene expression and DNA methylation analysis in primary and relapsed ependymoma tumors, to identify chromosomal conformations and regulatory mechanisms associated with aberrant gene expression. In particular, we observe the formation of new topologically associating domains ('neo-TADs') caused by structural variants, group-specific 3D chromatin loops, and the replacement of CTCF insulators by DNA hyper-methylation. Through inhibition experiments, we validate that genes implicated by these 3D genome conformations are essential for the survival of patient-derived ependymoma models in a group-specific manner. Thus, this study extends our ability to reveal tumor-dependency genes by 3D genome conformations even in tumors that lack targetable genetic alterations.

The first few months after birth, when a child begins to interact with the environment, are critical to human brain development. The human frontal lobe is important for social behavior and executive function; it has increased in size and complexity relative to other species, but the processes that have contributed to this expansion are unknown. Our studies of postmortem infant human brains revealed a collection of neurons that migrate and integrate widely into the frontal lobe during infancy. Chains of young neurons move tangentially close to the walls of the lateral ventricles and along blood vessels. These cells then individually disperse long distances to reach cortical tissue, where they differentiate and contribute to inhibitory circuits. Late-arriving interneurons could contribute to developmental plasticity, and the disruption of their postnatal migration or differentiation may underlie neurodevelopmental disorders.

Rates and characteristics of intracerebral cavernous malformations after cranial radiation therapy remain poorly understood. Herein we report on intracerebral cavernous malformations detected on follow-up imaging in pediatric cancer patients who received cranial radiation therapy at age ≤18 years from 1980 to 2009. Through chart reviews (n = 362) and phone interviews (n = 104) of a retrospective cohort, we identified 10 patients with intracerebral cavernous malformations. The median latency time for detection of intracerebral cavernous malformations after cranial radiation therapy was 12 years (range 1-24 years) at a median age of 21.4 years (interquartile range = 15-28). The cumulative incidence was 3% (95% confidence interval 1%-8%) at 10 years post cranial radiation therapy and 14% (95% confidence interval 7%-26%) at 15 years. Three patients underwent surgical resection. Two surgical specimens were pathologically similar to sporadically occurring intracerebral cavernous malformations; one was consistent with capillary telangiectasia. Intracerebral cavernous malformations are common after cranial radiation therapy and can show a spectrum of histologic features.

Central nervous system (CNS) tumors are now the most common type of solid tumor in individuals aged 0–19 years, with an incidence rate in the United States around 5 per 100,000, accounting for about 1 out of 4 childhood cancers. Pediatric pathologists encounter brain tumor cases with varying frequency, but many of these encounters begin in the context of intraoperative consultation or "frozen section." This review provides an overview of the technical aspects of intraoperative consultation specific to, or more helpful in, CNS tumors, emphasizing helpful cytologic and histologic features of the more commonly encountered pediatric CNS tumors, and illustrating some common diagnostic pitfalls and how these may be avoided. [ABSTRACT FROM AUTHOR]

Since the 1990s, the sheer number of defined central nervous system (CNS) embryonal tumor entities has continuously increased, with the trend accelerating in the most recent editions of the World Health Organization (WHO) Classification of Tumours of the CNS. The introduction of increasingly specific tumor groups is an effort to create more internally homogeneous categories, to allow more precise prognostication, and potentially to develop targeted therapies. However, these ever-smaller categories within an already rare group of tumors pose a challenge for pediatric pathologists. In this article we review the current categorization of non-medulloblastoma CNS embryonal tumors (including atypical teratoid/rhabdoid tumor, cribriform neuroepithelial tumor, embryonal tumor with multilayered rosettes, CNS neuroblastoma, FOXR2 -activated, and CNS tumor with BCOR internal tandem duplication) and provide an overview of available ancillary techniques to characterize these tumors. We provide a practical approach to workup and development of an integrated diagnosis for CNS embryonal tumors. [ABSTRACT FROM AUTHOR]

Tumor classification in neuropathology is a dynamic and complex topic, with many changes emerging in the past 5 years, up to and including the 2021 publication of the 5th edition of the World Health Organization Classification of Tumours of the Central Nervous System (CNS). For pediatric pathologists who will encounter brain tumors with varying frequency, it is important to understand the principles of these classification updates, particularly the inclusion of molecular genetic features and development of a layered, or integrated, diagnosis. This issue of Perspectives in Pediatric Pathology is dedicated to the examination of pediatric brain tumors, and features articles on intraoperative diagnosis and updated information on molecular-based classification for pediatric glial, glioneuronal, ependymal, and embryonal tumors of the CNS. [ABSTRACT FROM AUTHOR]

This research letter discusses a case series of pediatric brain tumors with a specific genetic fusion called MN1::BEND2. The study found that these tumors did not exhibit the typical features of astroblastoma, a type of brain tumor. However, the tumors did show DNA methylation profiles consistent with astroblastoma. The study emphasizes the need for further investigation and optimal treatment for these types of tumors. It also highlights the importance of accurate diagnosis and the need for more research on the clinical responses and long-term outcomes of pediatric patients with MN1-altered tumors. [Extracted from the article]