Jeremy Jones

Clofarabine salvage therapy in refractory multifocal histiocytic disorders, including Langerhans cell histiocytosis, juvenile xanthogranuloma and Rosai-Dorfman disease

Existing therapies for recurrent or refractory histiocytoses, including Langerhans cell histiocytosis (LCH), juvenile xanthogranuloma (JXG), and Rosai–Dorfman disease (RDD), have limited effectiveness. We report our experience with using clofarabine as therapy in children with recurrent or refractory histiocytic disorders, including LCH (11 patients), systemic JXG (4 patients), and RDD (3 patients).

Implications of Tumor Location on Subtypes of Medulloblastoma

Medulloblastoma (MB) comprises of four molecular subtypes, Sonic hedgehog (SHH), Wingless (WNT), Groups 3 and 4. WNT‐subtype MBs were found to arise from midline of the brainstem occupying the fourth ventricle while SHH‐subtype occupied the cerebellar hemisphere in a small subset of patients.

Long-term outcome of centrally located low-grade glioma in children

Optimal management of children with centrally located low‐grade glioma (LGG) is unclear. Initial interventions in most children are chemotherapy in younger and radiation therapy (RT) in older children. A better understanding of the inherent risk factors along with the effects of interventions on long‐term outcome can lead to reassessment of the current approaches to minimize long‐term morbidity.

Anaplastic ganglioglioma arising from a Lhermitte-Duclos-like lesion: Case report

The authors report the case of a 7-year-old boy with a history of developmental delay who presented with aggressive behavior. A magnetic resonance (MR) image showed a mass lesion originating from the cerebellar vermis with an atypical folial pattern and contrast enhancement. Histologically, the subtotally resected specimen consisted mostly of neuropil with nodular foci of ganglion cells. Lhermitte-Duclos disease (LDD) was diagnosed in the patient. A retrospective review of the tissue sections showed a nidus of associated astrocytic proliferation, suggesting a diagnosis of ganglioglioma. Five years later, the patient experienced an altered mental state and a facial droop. An MR image revealed a cerebellar mass with cystic areas and an enhancing nodule. The resected tissue specimen consisted primarily of a mixed proliferation of glial and ganglion cells consistent with a ganglioglioma. Two years later, a third craniectomy was performed in the patient for worsening headache and ataxia. Histologically, the tumor showed progressive anaplasia and was most accurately classified as an anaplastic ganglioglioma. Immunohistochemically, most of the tumor cells were immunoreactive for anti-phospho-mammalian target of rapamycin (mTOR) and phospho-S6 ribosomal protein antibodies. In contrast, the subpopulation of neoplastic ganglion cells in the tissue, particularly from the first surgery, did not express phosphatase and tensin homolog deleted from chromosome 10 (PTEN). This immunohistochemical pattern suggests that the large dysplastic ganglion cells (the gangliocytomatous component) forming the greater part of the lesion were associated with activation of the phosphatidylinositol 3-kinase-PTEN/Akt/mTOR signaling pathway, a feature previously reported in LDD. This case represents the first report of an anaplastic ganglioglioma arising in an LDD-like lesion.

Laryngeal ultrasound and pediatric vocal fold nodules

The term vocal fold nodules refers to bilateral thickening of the membranous folds with minimal impairment of the vibratory properties of the mucosa. Nodules are thought to be related to repetitive mechanical stress, associated with voice use patterns. Diagnosis is typically made in the office via either rigid or flexible laryngeal stroboscopy. Depending on the individual child, obtaining an optimal view of the larynx can be difficult if not impossible. Recent advances in high‐frequency ultrasonography allows for transcervical examination of laryngeal structures. The goal of this project was to determine if laryngeal ultrasound (LUS) can be used to identify vocal fold nodules in dysphonic children.

Current Role of Fetal Magnetic Resonance Imaging in Neurologic Anomalies

Magnetic resonance imaging (MRI) is used increasingly to image the fetus when important questions remain unanswered after ultrasonography, which might occur particularly with abnormal amniotic fluid volumes, difficult fetal lie or position, and maternal obesity. Ultrasonography also has limitations due to sound attenuation by bone, such as within the cranium and spine, and therefore MRI has a real advantage in delineating potentially complex neuroanatomical relationships. This article outlines current MRI protocols for evaluation of the fetal neural axis, describes indications for the use of MRI in the fetal brain and spine, and provides examples to illustrate the uses of available fetal sequences.

Utility of whole exome sequencing in evaluation of juvenile motor neuron disease

This case report focuses on identifying novel mutations in juvenile motor neuron disease and emphasizes the significance of whole exome sequencing (WES).

Dramatic clinical and radiographic response to BRAF inhibition in a patient with progressive disseminated optic pathway glioma refractory to MEK inhibition

ABSTRACT While clinical and radiographic responses to agents targeting the mitogen-activated protein kinases (MAPK) pathway have been repor-ted in pediatric low-grade gliomas (LGG), early phase trials indicate refractoriness to these medications in some of these patients. We report a patient with disseminated LGG with the BRAFV600E mutation, which was refractory to selumetinib, a MEK inhibitor, but subsequently showed immediate clinical and radiographic response to dabrafenib, a BRAF inhibitor, with sustained effect for 9 months prior to clinical progression. In LGGs, treatment resistance to one agent targeting the MAPK pathway might not imply refractoriness to other agents targeting this pathway.

CNS Langerhans cell histiocytosis: Common hematopoietic origin for LCH-associated neurodegeneration and mass lesions

Central nervous system Langerhans cell histiocytosis (CNS‐LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH‐ND) of unknown etiology. The goal of this study was to define the mechanisms of pathogenesis that drive CNS‐LCH.

Significant response of pituitary carcinoma to carboplatin, leucovorin and fluorouracil chemotherapy: a pediatric case report and review of the literature

that resulted in complete radiological resolution and clinical improvement in hypercortisolism in an adolescent with Cushing disease and pituitary carcinoma. A 14-year-old female presented in October 2004 with decreased right eye vision, amenorrhea, and headaches. Magnetic resonance imaging (MRI) of the brain revealed a 2 × 2 cm sellar/suprasellar mass involving the optic pathway. Initial biopsy was misinterpreted as a low grade glioma and she was started on vincristine and carboplatin. In January 2005, brain MRI showed an increase in tumor size, a subtotal resection was performed and subsequent referral to our institution. Pathology showed an ACTH positive epithelioid neoplasm with neuroendocrine features consistent with pituitary adenoma. While taking dexamethasone, her random cortisol and ACTH levels were abnormally within normal range: 11.8 μg/dl (normal 3–21 μg/dl) and 17 pg/ ml (normal 5–27 pg/ml), respectively. A 24-h urine free cortisol level was not done. She was cushingoid and had a residual mass involving the right side of the sella, the right suprasellar cistern and the right cavernous sinus inseparable from the right optic pathway. She had no light perception in the right eye and a superotemporal visual field defect with 20/20 acuity in the left eye. In April 2005, she had another partial resection followed by RT (4680 cGy). In August 2006, metastatic tumor was detected in the right frontal lobe, which was completely resected and treated with 5400 cGy RT. In August 2007, she was treated with capecitabine (1 gm bid days 1–14) and temozolomide (200 mg bid days 1–5) for a new metastatic recurrence at the clivus and the suprasellar area associated with rising ACTH levels and worsening hypercortisolism. After 2 cycles, her left eye vision decreased to “light perception only” associated with radiological (Fig. 1) and biochemical progression. She was then started on carboplatin 500 mg/m2 on Day 1 and 5-FU 500 mg/m2 To the Editor,