A Case Report of Infant-Type Hemispheric Glioma with a Novel GAB1-ABL2 Kinase Fusion Treated with Dasatinib.

INTRODUCTION: Infant-type hemispheric glioma (IHG) is a rare form of cancer that affects newborns and infants. It is classified as a pediatric-type high-grade glioma and typically harbors receptor tyrosine kinase (RTK) gene fusions. Here, we present the finding of a novel gene fusion IHG treated with a targeted therapy that has yet to be implemented for any other IHG case to date. CASE PRESENTATION: We report the case of a 12-month-old boy with IHG who presented with obstructive hydrocephalus due to a large mass in the right frontal lobe. The patient initially underwent mass resection, but subsequent imaging showed rapid interval progression of the residual tumor. Comprehensive molecular analysis of the tumor tissue revealed a novel GAB1-ABL2 gene fusion, and the patient was started on dasatinib, an ABL kinase inhibitor. Shortly after initiation of dasatinib treatment, there was a significant reduction in tumor size and enhancement, followed by stabilization of disease. DISCUSSION: The patient's robust response to treatment suggests that dasatinib is an effective targeted therapy for IHG harboring a GAB1-ABL2 gene fusion. This finding may inform future investigations into the disease processes of IHG and help guide the diagnosis and treatment of IHG in the absence of previously identified gene fusions, improving clinical management of this vulnerable patient population.

A nine-month-old boy with regression of milestones and severe constipation: an unusual case of a large spinal NTRK1 fusion pilocytic astrocytoma.

INTRODUCTION: Pilocytic astrocytoma, a World Health Organization grade 1 tumor, is the most common brain tumor in children between 5 and 14 years of age and the second most common in children younger than 5 and older than 14. Although classical to the cerebellum and hypothalamic regions, it can also arise in the spinal cord. Larotrectinib, a selective inhibitor of tropomyosin receptor kinase, has been effective in pediatric tumors with NTRK fusion mutations in children as young as 1-month-old. CASE: We share the case of a 9-month-old boy who presented with a 4-month history of regression of his milestones and severe constipation who was found to have a large spinal pilocytic astrocytoma with multiple intracranial periventricular lesions.

PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum.

Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens.

Low-grade glioma: A rare second tumor in retinoblastoma survivors.

Retinoblastoma survivors with a germline RB1 mutation are at elevated risk for secondary (nonocular) malignancy, but their risk for low-grade glioma (LGG) is unknown. We performed a retrospective review of the Memorial Sloan Kettering Cancer Center and the NCI databases that revealed that three of the 837 5-year survivors of hereditary retinoblastoma were diagnosed with an LGG and a fourth patient (but unilateral and without a germline mutation) was identified at another center. Retinoblastoma survivors may be at increased risk for LGG.

Life-Threatening Headaches in Children: Clinical Approach and Therapeutic Options.

Life-threatening headaches in children can present in an apoplectic manner that garners immediate medical attention, or in an insidious, more dangerous form that may go unnoticed for a relatively long period of time. The recognition of certain clinical characteristics that accompany the headache should prompt recognition and referral to an institution equipped with neuroimaging facilities, pediatric neurosurgeons, and neurologists. Thunderclap headaches, which reach a peak within a very short period of time, may be the presenting feature of conditions such as arterial dissection, venous sinus thrombosis, and reversible cerebral vasoconstriction syndrome, which can be addressed by specific pharmacological options instituted in an intensive care setting. On the other hand, subacute to chronic headaches that are accompanied by focal neurological signs, such as abducens nerve palsy, restriction of upward gaze, or papilledema, may be indicative of the need for urgent imaging and neurosurgical referral. [Pediatr Ann. 2018;47(2):e74-e80.].