TULIPs decorate the three-dimensional genome of PFA ependymoma.

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues.

Pediatric Myxopapillary Ependymomas: A Clinicopathologic Evaluation.

Myxopapillary ependymomas (MPEs) have an indolent clinical course, corresponding to World Health Organization Grade I. A total of 13 pediatric MPEs have been reported in the literature with "anaplastic features," including elevated proliferative activity (≥5 mitoses/10 high-power fields), necrosis, and microvascular proliferation. No consensus exists regarding the prognostic significance of such features.

Clinical Outcomes of May-Thurner Syndrome in Pediatric Patients: A Single Institutional Experience.

 May-Thurner syndrome (MTS) is a vascular anatomic variant resulting in compression of the left common iliac vein by the right common iliac artery, affecting approximately 22% of the population. In adults, following acute deep vein thrombosis (DVT) of the iliofemoral veins, the incidence of postthrombotic syndrome (PTS) and recurrent DVT are high if treated with anticoagulation alone, warranting adjunctive treatment with thrombolysis and stent placement. However, there is paucity of literature documenting the course of treatment and associated outcomes in pediatric patients with MTS.

Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma.

Over the past decade, wingless-activated (WNT) medulloblastoma has been identified as a candidate for therapy de-escalation based on excellent survival; however, a paucity of relapses has precluded additional analyses of markers of relapse. To address this gap in knowledge, an international cohort of 93 molecularly confirmed WNT MB was assembled, where 5-year progression-free survival is 0.84 (95%, 0.

Recurrent noncoding U1 snRNA mutations drive cryptic splicing in SHH medulloblastoma.

In cancer, recurrent somatic single-nucleotide variants-which are rare in most paediatric cancers-are confined largely to protein-coding genes. Here we report highly recurrent hotspot mutations (r.3A>G) of U1 spliceosomal small nuclear RNAs (snRNAs) in about 50% of Sonic hedgehog (SHH) medulloblastomas.

Desmoplastic Infantile Ganglioglioma: A MAPK Pathway-Driven and Microglia/Macrophage-Rich Neuroepithelial Tumor.

MAPK pathway activation has been recurrently observed in desmoplastic infantile ganglioglioma/astrocytoma (DIG/DIA) with reported disproportionally low mutation allele frequencies relative to the apparent high tumor content, suggesting that MAPK pathway alterations may be subclonal. We sought to expand the number of molecularly profiled cases and investigate if tumor cell composition could account for the observed low mutation allele frequencies. Molecular (targeted neuro-oncology next-generation sequencing/RNA sequencing and OncoScan microarray) and immunohistochemical (CD68-PGM1/CD163/CD14/CD11c/lysozyme/CD3/CD20/CD34/PD-L1) studies were performed in 7 DIG.

Case-based review: atypical teratoid/rhabdoid tumor.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare CNS cancer that typically occurs in children younger than 3 years of age. Histologically, AT/RTs are embryonal tumors that contain a rhabdoid component as well as areas with primitive neuroectodermal, mesenchymal, and epithelial features. Compared to other CNS tumors of childhood, AT/RTs are characterized by their rapid growth, short symptomatic prodrome, and large size upon presentation, often leading to brain compression and intracranial hypertension requiring urgent intervention.

EBV-PTLD, Adenovirus, and CMV in Pediatric Allogeneic Transplants With Alemtuzumab as Part of Pretransplant Conditioning: A Retrospective Single Center Study.

The risk of viral infections and reactivation occurring in the setting of pediatric allogeneic hematopoietic stem cell transplantation is a concern in the pediatric patient, especially with the use of Alemtuzumab (Campath) as a conditioning agent. The purpose of this study was to determine the incidence of Epstein-Barr virus posttransplant lymphoproliferative disorder (EBV-PTLD), cytomegalovirus (CMV), and adenovirus among pediatric recipients of alemtuzumab at our institution. We found that EBV-PTLD occurred in 2.

Anaplastic astrocytoma with piloid features, a novel molecular class of IDH wildtype glioma with recurrent MAPK pathway, CDKN2A/B and ATRX alterations.

Tumors with histological features of pilocytic astrocytoma (PA), but with increased mitotic activity and additional high-grade features (particularly microvascular proliferation and palisading necrosis) have often been designated anaplastic pilocytic astrocytomas. The status of these tumors as a separate entity has not yet been conclusively demonstrated and molecular features have only been partially characterized. We performed DNA methylation profiling of 102 histologically defined anaplastic pilocytic astrocytomas.

Cross-Cultural Medical Care Training and Education: a National Survey of Pediatric Hematology/Oncology Fellows-in-Training and Fellowship Program Directors.

Pediatric hematologists/oncologists face complex situations such as breaking bad news, treatment/clinical trials discussions, and end-of-life/hospice care. With increasing diversity in patient and physician populations, cultural competency and sensitivity training covering different aspects of pediatric hematology/oncology (PDHO) care can help improve health care delivery and reduce disparities. Though it is considered a required component of fellowship training, there is no clearly defined curriculum meant specifically for PDHO fellows-in-training (PDHO-F).

Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas.

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown. Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510).

Optimal radiotherapy target volumes in intracranial nongerminomatous germ cell tumors: Long-term institutional experience with chemotherapy, surgery, and dose- and field-adapted radiotherapy.

Purpose: To evaluate patterns of failure after multimodality treatment of nongerminomatous germ cell tumors (NGGCTs).

Materials And Methods: We retrospectively reviewed records of 34 patients diagnosed with primary intracranial NGGCT between 1988 and 2014.

Results: Thirty-four patients received induction chemotherapy followed by radiation with or without surgery.

Intertumoral Heterogeneity within Medulloblastoma Subgroups.

While molecular subgrouping has revolutionized medulloblastoma classification, the extent of heterogeneity within subgroups is unknown. Similarity network fusion (SNF) applied to genome-wide DNA methylation and gene expression data across 763 primary samples identifies very homogeneous clusters of patients, supporting the presence of medulloblastoma subtypes. After integration of somatic copy-number alterations, and clinical features specific to each cluster, we identify 12 different subtypes of medulloblastoma.

Cross-Cultural Care Training for Pediatric Hematology/Oncology Fellows.

Introduction: Physicians are entrusted with the medical care of culturally and socially diverse patient populations. In addition, pediatric hematologists/oncologists are faced with the challenge of taking care of children with life-threatening and complex conditions. We implemented a cross-cultural care training curriculum for our pediatric hematology/oncology fellows with the goal of preparing them to handle complex clinical situations while navigating different social and cultural belief systems.

Recurrent copy number alterations in low-grade and anaplastic pleomorphic xanthoastrocytoma with and without BRAF V600E mutation.

Pleomorphic xanthoastrocytoma (PXA) is a rare localized glioma characterized by frequent BRAF V600E mutation and CDKN2A/B deletion. We explored the association of copy-number variants (CNVs) with BRAF mutations, tumor grade, and patient survival in a cohort of 41 PXA patients using OncoScan chromosomal microarray. Primary resection specimens were available in 38 cases, including 24 PXA and 14 anaplastic PXA (A-PXA), 23 BRAF V600E mutant tumors (61%).

Molecular Modeling and Functional Analysis of Exome Sequencing-Derived Variants of Unknown Significance Identify a Novel, Constitutively Active FGFR2 Mutant in Cholangiocarcinoma.

Purpose: Genomic testing has increased the quantity of information available to oncologists. Unfortunately, many identified sequence alterations are variants of unknown significance (VUSs), which thus limit the clinician's ability to use these findings to inform treatment. We applied a combination of in silico prediction and molecular modeling tools and laboratory techniques to rapidly define actionable VUSs.

Lemierre Syndrome: A Retrospective Study of the Role of Anticoagulation and Thrombosis Outcomes.

Lemierre syndrome (LS) is a multisystemic infection beginning in the oropharynx and leading to thrombosis of the internal jugular vein (IJV) with septic emboli and potential thrombotic extension to the central nervous system. Although patient outcomes have improved with early initiation of antimicrobial therapies, there is no consensus regarding the role of anticoagulation in LS. To better define the role of anticoagulation therapy in LS and determine whether anticoagulation improves thrombosis outcomes, we conducted a retrospective chart review of pediatric and adult patients diagnosed with LS and managed at our institution from January 1998 to December 2014.

Measuring pediatric hematology-oncology fellows' skills in humanism and professionalism: A novel assessment instrument.

Background: Educators in pediatric hematology-oncology lack rigorously developed instruments to assess fellows' skills in humanism and professionalism.

Procedure: We developed a novel 15-item self-assessment instrument to address this gap in fellowship training. Fellows (N = 122) were asked to assess their skills in five domains: balancing competing demands of fellowship, caring for the dying patient, confronting depression and burnout, responding to challenging relationships with patients, and practicing humanistic medicine.

A retrospective review of pediatric antiphospholipid syndrome and thrombosis outcomes.

: Pediatric antiphospholipid syndrome (APS) is characterized by vascular thromboses and multisystem involvement associated with persistently positive antiphospholipid antibodies testing. There is limited literature regarding risk factors for development of thrombosis and long-term thrombotic outcomes in pediatric APS. The objective of our study was to review our institutional experience with pediatric APS and thrombosis outcomes.

Neonatal renal vein thrombosis: role of anticoagulation and thrombolysis--an institutional review.

Neonatal renal vein thrombosis (NRVT) is a rare thromboembolic complication in the neonatal period, and sequelae from renal dysfunction can cause significant morbidity. The authors retrospectively reviewed 10 patients with NRVT treated at their institution. The majority of the cohort were male (n = 9), preterm (n = 6), and had unilateral NRVT (n = 6).