Norrie disease with a spontaneously shrinking choroid plexus abnormality: a case report.

Background: Norrie disease is a genetic disorder of the retina characterized by impaired retinal vascular development leading to retinal detachment and blindness. Non-retinal manifestations of the disorder include intellectual disability and seizure disorders. However, to date, no association with neurological mass lesions has been described.Materials and methods: Case reporResults: Here, we report a case of a patient with Norrie disease who presented with an enhancing mass of the choroid plexus that spontaneously diminished in size. Conclusion: This report suggests watchful waiting as a reasonable clinical approach to choroid plexus lesions in patients with Norrie disease.

In silico analysis identifies a putative cell-of-origin for BRAF fusion-positive cerebellar pilocytic astrocytoma.

Childhood cancers are increasingly recognized as disorders of cellular development. This study sought to identify the cellular and developmental origins of cerebellar pilocytic astrocytoma, the most common brain tumor of childhood. Using publicly available gene expression data from pilocytic astrocytoma tumors and controlling for driver mutation, a set of developmental-related genes which were overexpressed in cerebellar pilocytic astrocytoma was identified. These genes were then mapped onto several developmental atlases in order to identify normal cells with similar gene expression patterns and the developmental trajectory of those cells was interrogated. Eight known neuro-developmental genes were identified as being expressed in cerebellar pilocytic astrocytoma. Mapping those genes or their orthologs onto mouse neuro-developmental atlases identified overlap in their expression within the ventricular zone of the cerebellar anlage. Further analysis with a single cell RNA-sequencing atlas of the developing mouse cerebellum defined this overlap as occurring in ventricular zone progenitor cells at the division point between GABA-ergic neuronal and glial lineages, a developmental trajectory which closely mirrors that previously described to occur within pilocytic astrocytoma cells. Furthermore, ventricular zone progenitor cells and their progeny exhibited evidence of MAPK pathway activation, the paradigmatic oncogenic cascade known to be active in cerebellar pilocytic astrocytoma. Gene expression from developing human brain atlases recapitulated the same anatomic localizations and developmental trajectories as those found in mice. Taken together, these data suggest this population of ventricular zone progenitor cells as the cell-of-origin for BRAF fusion-positive cerebellar pilocytic astrocytoma.

Atypical Teratoid Rhabdoid Tumor of the Cauda Equina in a Child: Report of a Very Unusual Case.

Atypical teratoid/rhabdoid tumors (AT/RT) are highly aggressive malignant primitive neoplasms that commonly occur in children younger than 2 years of age. The prognosis is generally dismal with a median survival time of <1 year. The majority of AT/RT occur in the posterior fossa and less frequently the supratentorium. Primary pediatric spinal AT/RT are exceedingly rare and only 15 cases have been reported to date. Here we report a very unusual case of primary spinal AT/RT extensively involving the spinal cord from T11 down to the cauda equina. In this patient, the tumor was highly aggressive and resulted in extensive dissemination into the nerve roots and paraspinal soft tissue rapidly resulting in the patient's death 1 month after diagnosis. to the best of our knowledge, this degree of involvement of the spine by a primary AT/RT has not been described before.

Dual diagnoses in 152 patients with Turner syndrome: Knowledge of the second condition may lead to modification of treatment and/or surveillance.

Turner syndrome is a sex chromosome abnormality in which a female has a single X chromosome or structurally deficient second sex chromosome. The phenotypic spectrum is broad, and atypical features prompt discussion of whether the known features of Turner syndrome should be further expanded. With the advent of clinical whole exome sequencing, there has been increased realization that some patients with genetic disorders carry a second genetic disorder, leading us to hypothesize that a "dual diagnosis" may be more common than suspected for Turner syndrome. We report five new patients with Turner syndrome and a co-occurring genetic disorder including one patient with Li-Fraumeni syndrome, Li-Fraumeni and Noonan syndrome, mosaic trisomy 8, pathogenic variant in RERE, and blepharophimosis-ptosis-epicanthanus inversus syndrome. We also undertook an extensive literature review of 147 reports of patients with Turner syndrome and a second genetic condition. A total of 47 patients (31%) had trisomy 21, followed by 36 patients (24%) had one of 11 X-linked disorders. Notably, 80% of the 147 reported patients with a dual diagnosis had mosaicism for Turner syndrome, approximately twice the frequency in the general Turner syndrome population. This article demonstrates the potential for co-occurring syndromes in patients with Turner syndrome, prompting us to recommend a search for an additional genetic disorder in Turner patients with unusual features. Knowledge of the second condition may lead to modification of treatment and/or surveillance. We anticipate that increased awareness and improved diagnostic technologies will lead to the identification of more cases of Turner syndrome with a co-occurring genetic syndrome.

Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation.

Disseminated glioneuronal tumors of childhood are rare. We present a retrospective IRB-approved review of the clinical course and frequency of BRAF mutations in disseminated glioneuronal tumors at two institutions. Defining features of our cohort include diffuse leptomeningeal-spread, often with a discrete spinal cord nodule and oligodendroglioma-like histologic features. Patients were identified through a pathology database search of all cases with disseminated low-grade neoplasms with an oligodendroglioma-like component. De-identified clinical information was collected by chart review and all imaging was reviewed. We retrieved the results of targeted genomic analyses for alterations in BRAF. Ten patients (aged 2-14 years) were identified from the Dana-Farber/Boston Children's Hospital and the Royal Children's Hospital, Melbourne pathology databases. Nine patients received chemotherapy. Eight patients are alive, although three have had episodes of progressive disease. We identified genomic alterations affecting the MAPK pathway in six patients. One patient had a germline RAF1 mutation and a clinical diagnosis of cardio-facio-cutaneous syndrome. BRAF duplications were identified in four and BRAF V600E mutation was identified in one. These data support the presence of targetable genomic alterations in this disease.

Transcriptome Analysis of Minimal Residual Disease in Subtypes of Pediatric B Cell Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related death in children and adolescents. Minimal residual disease (MRD) is a strong, independent prognostic factor. The objective of this study was to identify molecular signatures distinguishing patients with positive MRD from those with negative MRD in different subtypes of ALL, and to identify molecular networks and biological pathways deregulated in response to positive MRD at day 46. We compared gene expression levels between patients with positive MRD and negative MRD in each subtype to identify differentially expressed genes. Hierarchical clustering was applied to determine their functional relationships. We identified subtype-specific gene signatures distinguishing patients with positive MRD from those with negative MRD. We identified the genes involved in cell cycle, apoptosis, transport, and DNA repair. We also identified molecular networks and biological pathways dysregulated in response to positive MRD, including Granzyme B, B-cell receptor, and PI3K signaling pathways.

Brief neurocognitive screening in youth with brain tumours: A preliminary investigation of the Lebby-Asbell Neurocognitive Screening Examination (LANSE).

PRIMARY OBJECTIVE: It is well-documented that survivors of paediatric brain tumour are at risk for neurocognitive deficits resulting in an increased interest in neurocognitive assessment for these youth. Given the scarcity of well-validated brief assessments for this purpose, this study examines the reliability and validity of a brief neurocognitive screening measure. RESEARCH DESIGN: Cross-sectional data on youth (aged 6-17.9) administered a brief neurocognitive screening device and broader neurocognitive batteries was collected via chart review to evaluate the reliability and validity of a brief neurocognitive screening device. METHODS AND PROCEDURES: Fifty-one youth with brain tumours and 26 youth with traumatic brain injury (TBI) were administered The Lebby-Asbell Neurocognitive Screening Examination (LANSE) during clinic visits. A sub-set of children were administered a more comprehensive neurocognitive evaluation and scores from the LANSE and these evaluations were compared to assess preliminary validity. MAIN OUTCOME AND RESULTS: Most LANSE sub-scales demonstrated adequate reliability and preliminary validity with some exceptions. Comparison of youth with brain tumours to those with a TBI revealed a similar pattern of potential neurocognitive impairment across several cognitive domains. CONCLUSIONS: This study demonstrates the preliminary reliability and validity of a brief neurocognitive screening examination for youth with brain tumours.

Newly Identified Characteristics and Suggestions for Diagnosis and Treatment of Diffuse Leptomeningeal Glioneuronal/Neuroepithelial Tumors: A Case Report and Review of the Literature.

Diffuse leptomeningeal glioneuronal tumor is unique for communicating hydrocephalus, diffuse leptomeningeal enhancement, cystic changes, absence of tumor cells in cerebral spinal fluid, and a cell population of both glial and neuronal copositivity. It has likely been misdiagnosed as mixed glioneuronal tumors, oligodendrogliomas, and neuroepithelial tumors. Children with signs of this tumor are often worked up for infection, rheumatologic disease, or disseminated primary malignancy, resulting in unnecessary testing and treatment. We describe a 14-year-old female with recurrent headaches, hydrocephalus, and diffuse leptomeningeal enhancement discovered to be neoplastic 1 year after initial presentation, owing to extensive and unrevealing infectious and immunologic workups. Biopsies revealed atypical cells with markers of both glial and neuronal cells, positivity for OLIG-2, and focal p53 positivity. Great response was seen with temozolomide and craniospinal irradiation. Additionally, we postulate additional diagnostic indicators that may aid in earlier diagnosis and treatment decisions.

Gastric metastasis from an alveolar soft part sarcoma in a child: case report and review of the literature.

The authors report a child with alveolar soft part sarcoma who developed significant anemia due to gastrointestinal blood loss. Evaluation revealed the source of bleeding as a gastric metastasis, which was successfully removed. A brief review of gastrointestinal involvement by alveolar soft part sarcoma is discussed.

Osteosarcoma tumor thrombus: a case report with a review of the literature.

Tumor thrombus arising from osteosarcoma is rare. We report the case of a 20-year-old man with proximal humerus osteosarcoma, accompanied by an extensive intravascular tumor thrombus extending into the heart. Our review of the literature found 14 previous reports on osteosarcoma with tumor thrombus. The combination of positron emission tomography and computed tomography is very useful in differentiating tumor thrombus from vascular thrombus, thereby avoiding unnecessary anticoagulation therapy. This same imaging combination can also be used to evaluate the response to treatment. Surgical resection of the tumor thrombus is highly recommended. The effect of tumor thrombus on survival is still unknown.

A rare case of peripheral neuropathy from relapse of acute lymphoblastic leukemia to the brachial plexus.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. ALL frequently involves the central nervous system and testicles, but has also been reported to metastasize to the liver and lung. We report a case of a 4-year-old African-American male with a previous history of ALL and hematopoietic stem cell transplant who presented with decreased arm movement and abdominal pain with relapse of primary disease into the brachial plexus and pancreas.

Angioedema associated with dihydropyridine calcium-channel blockers in a child with Burkitt lymphoma.

PURPOSE: A case of severe macroglossia and angioedema in a child with Burkitt lymphoma who was treated with two dihydropyridine calcium-channel blockers is reported. SUMMARY: An eight-year-old white boy arrived at the pediatric emergency department with complaints of abdominal pain and distention after an episode of mild abdominal trauma. Physical examination results were significant for diffuse abdominal tenderness and distention, with a large palpable mass in the right quadrants. Computed tomography revealed a large abdominal mass, and a biopsy confirmed a diagnosis of Burkitt lymphoma. Before initiation of chemotherapy, the child developed tumor lysis syndrome, with subsequent renal failure and cardiorespiratory compromise. Once the patient was stabilized and sedated on mechanical ventilation, tumor-directed chemotherapy was initiated, and rapid tumor regression ensued. To control episodes of hypertension, nicardipine was initiated and titrated to achieve the blood pressure goals. Three days after initiation of nicardipine therapy, the child developed facial swelling and significant, protruding macroglossia. Eight days after nicardipine initiation, a tracheotomy was required due to upper airway obstruction; at that time, the patient was converted to amlodipine administered via nasogastric tube for continued blood pressure control. The boy's macroglossia persisted for another 18 days, until a multi-disciplinary drug therapy review resulted in the discontinuation of amlodipine. Within one week of the withdrawal of amlodipine, the child's macroglossia was completely resolved. CONCLUSION: An eight-year-old boy with Burkitt lymphoma developed severe macroglossia and angioedema when treated with nicardipine. The reaction persisted throughout treatment with amlodipine and resolved quickly after amlodipine was withdrawn.

Small molecule inhibitors in children with malignant gliomas.

Pediatric high grade gliomas (HGG) remain difficult to cure despite recent advances in imaging, neurosurgery, and radiation. Current treatment modalities have demonstrated only modest survival benefit. Research utilizing molecular biologic techniques reveals that the phenotype of HGG is complex and results from dysregulation of numerous inter-related cellular pathways. Knowledge of potential molecular targets along dysregulated pathways has led to the development of novel and highly specific targeted therapies, which include small molecule inhibitors. This article will review small molecule inhibition of cellular pathways involved in gliomagenesis, challenges to small molecule therapy, and future directions in the use of this therapy.

Effect of noscapine and vincristine combination on demyelination and cell proliferation in vitro.

Peripheral neuropathy is a common, dose-limiting side effect of vincristine, a frontline therapy for acute lymphoblastic leukemia. Combination chemotherapy that reduces the neurotoxicity without compromising the efficacy of vincristine would improve patient outcomes. We performed in vitro studies using a combination of microtubule-binding antimitotics, noscapine and vincristine. In cell cultures containing neurons, astrocytes, and oligodendrocytes, vincristine caused demyelination as shown by transmission electron microscopy. A combination of vincristine and noscapine protected against demyelination. Human acute lymphoblastic and acute myelogenous leukemia cell lines CCRF-CEM and HL-60, respectively, were used to determine the antiproliferative effect of this novel drug combination. Vincristine and noscapine decreased cell proliferation with IC(50) concentrations of 1 nM and 20 microM, respectively. Analysis of dose-effect relationships using isobolograms and combination indices demonstrated that noscapine acts synergistically with vincristine. Thus, noscapine is a promising candidate for use with vincristine to decrease neurotoxicity and enhance antineoplastic effectiveness.