Intracranial Germinoma in Two Caucasian American Siblings With Autism Spectrum Disorder.

Intracranial germ cell tumors (IGCTs) comprise 3% to 5% of all pediatric brain tumors in the West, with a significantly higher prevalence in Asia. Although these tumors are histologically diverse, repeated somatic variants have been demonstrated. Chromosomal aneuploidies, such as Klinefelter and Down syndromes, are associated with IGCTs, but no familial germline tumor syndromes are currently known. Here, we report the novel case of 2 American siblings with underlying autism spectrum disorder who developed intracranial germinoma within months of each other, in the absence of external risk factors. Extensive genetic testing was performed, including karyotyping, chromosomal microarray, and whole exome and whole genome sequencing, and did not identify any variants accounting for the phenotypes. Despite the absence of overlapping variants, a recent retrospective review demonstrated a threefold greater prevalence of autism spectrum disorder in patients with intracranial germinoma compared with national prevalence. This report highlights the complexity of tumor development, as well as the need for further research regarding IGCTs in a neurodivergent population.

Central Nervous System Tumor With BCL6 Corepressor Internal Tandem Duplication: Treatment Course of a Long-term Survivor.

Central nervous system (CNS) tumor with BCL6 corepressor (BCOR) internal tandem duplication (ITD) is a newly described CNS tumor, characterized by in-frame ITDs of the BCOR gene. There is no standard practice regarding the management of this tumor. We report the clinical course of a 6-year-old boy who presented to the hospital with worsening headaches. Computed tomography scan showed a large right-sided parietal supratentorial mass and brain magnetic resonance imaging confirmed a 6×8×6.7 cm lobulated, solid but heterogeneous mass in the right parieto-occipital region. While initial pathology suggested a WHO grade 3 anaplastic meningioma, additional investigation with molecular analysis confirmed the diagnosis of high-grade neuroepithelial tumor with BCOR exon 15 ITD. This diagnosis was renamed CNS tumor with BCOR ITD in the 2021 WHO CNS tumor classification. The patient received 54 Gy of focal radiation and has no evidence of disease recurrence after 48 months from the end of treatment. As this is a newly discovered entity with only a few previous reports in the scientific literature, this report presents a unique treatment for this CNS tumor compared with those previously described.

Juvenile Xanthogranuloma of the Pancreas in a Pediatric Patient Mimicking Pancreatic Neoplasm With High CA 19-9: Case Report and Literature Review.

Juvenile xanthogranuloma (JXG) is a rare, non-Langerhans cell histiocytosis. It is usually a benign and self-limiting condition. The most common sites are skin and soft tissue. Pancreatic involvement is extremely rare. We present an unusual case of a 13-month-old female child with JXG of the pancreas and elevated cancer antigen 19-9. JXG should always be considered as a differential diagnosis for pediatric patients presenting with a pancreatic mass, solid and/or cystic in nature. Therefore, avoiding unnecessary invasive diagnostic procedures.

Ongoing Response in a Multiply Relapsed Metastatic Posterior Fossa Ependymoma A After Vorinostat and Concomitant Irradiation.

Posterior fossa ependymomas A confer the worst prognosis among all subtypes. They demonstrate distinct epigenetic changes, which can be targeted with epigenetic modifiers like histone deacetylase inhibitors (Vorinostat). We describe a 3-year-old male diagnosed with a posterior fossa ependymoma who had a number of recurrences requiring multimodal therapy. Molecular analysis demonstrated a BCL-6 corepressor mutation, and methylation profiling matched with posterior fossa ependymomas A. He received craniospinal irradiation and focal boost with Vorinostat. Serial imaging after irradiation revealed a progressively decreasing tumor burden with nearly complete resolution of disease at 15 months. Histone deacetylase inhibitors demonstrate promise in treatment of carefully selected cases of ependymoma.

Nivolumab in the Treatment of Recurrent or Refractory Pediatric Brain Tumors: A Single Institutional Experience.

Successful use of immune checkpoint inhibitors in a variety of cancers has generated interest in using this approach in pediatric brain tumors. We performed a retrospective review of 10 consecutive children (6 boys, 4 girls; ages, 2 to 17 y), with recurrent or refractory pediatric brain tumors (5 high-grade glioma, 1 low-grade glioma, pineoblastoma, medulloblastoma, ependymoma, and CNS embryonal tumor, NOS) treated at Rady Children's Hospital San Diego from 2015 to 2017 with the immune checkpoint inhibitor nivolumab (3 mg/kg every 2 wk). Eight of 10 patients received prior chemotherapy and 9 radiation therapy. Nine patients had radiographic disease progression (median, 2.5 doses). Median time to progression was 5.5 weeks (1.6 to 24 wk). Three patients (2 with high-grade glioma, 1 with CNS embryonal tumor NOS) showed a partial response to treatment at the primary tumor site and 2 of 3 had progression of metastatic disease. Grade 2 toxicities were observed without dose limiting side effects. Tumor mutation burden (TMB) was low to intermediate (median, 1.3; range, 0 to 6.3). Median survival for PD-L1 positive patients was 13.7 weeks versus 4.2 weeks for PD-L1 negative patients (ρ=0.08) nivolumab was well tolerated in our series of pediatric recurrent brain tumors with some transient partial responses in patients with positive PD-L1 expression and higher TMB. Our findings suggest that the use of immune checkpoint inhibitors in pediatric brain tumor patients should be limited to those with elevated PD-L1 expression and TMB.

Single-agent bevacizumab in the treatment of recurrent or refractory pediatric low-grade glioma: A single institutional experience.

INTRODUCTION: Bevacizumab-based therapy has been demonstrated to be effective in the treatment of refractory or recurrent pediatric low-grade glioma (LGG); however its efficacy as a single agent is less understood. METHODS: We report our experience with single-agent bevacizumab for the treatment of recurrent or refractory LGG treated with either standard 2 week dosing (10 mg/kg/dose every 2 weeks) or with a standard 2 week dosing followed by an increased interval dosing (10 mg/kg/dose every 4 weeks). RESULTS: From 2012 to 2017, 15 patients (five males and 10 females) with recurrent/refractory LGG (nine suprasellar, three thalamic, two brainstem, and one intramedullary spinal cord) were treated with a total of 156 doses of bevacizumab (115 every 2 week dosing, 41 every 4 week dosing, median 10 doses). Patients were refractory to a median of one nonsurgical therapy (range 0-3) prior to treatment with bevacizumab. Twelve of 15 demonstrated radiographic response (three complete, nine partial, and three stable disease). Significant clinical responses including improved visual fields (four), cranial neuropathy (three3), strength (seven), and gait (two) were observed. Bevacizumab was discontinued in 12 patients (resolution, one; disease stability, seven; progression, two; toxicity, one; and other, one) and three patients continue to receive monthly bevacizumab. Eleven patients eventually had radiographic progression (median 5 months, range 0.5-31) without clinical progression, and four of five receiving bevacizumab rechallenge had lpartial response. CONCLUSION: Single-agent bevacizumab is efficacious in the management of recurrent or refractory pediatric LGG with radiographic and clinical responses similar to those reported for bevacizumab-based therapies.