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Neurocutaneous melanocytosis (NCM) is characterized by melanocyte deposition in the leptomeninges and brain parenchyma, primarily occurring in children with large or giant congenital melanocytic nevi (LCMN) or multiple congenital melanocytic nevi. Patients with NCM may develop hydrocephalus and increased intracranial pressure, which can be managed with ventriculoperitoneal (VP) shunting. We present the case of a 16‐month‐old girl who developed peritoneal carcinomatosis and malignant ascites following VP shunting for hydrocephalus secondary to NCM to increase awareness of this rare, but serious, complication of cerebrospinal fluid diversion. [ABSTRACT FROM AUTHOR]

Neuro-oncology is a rapidly evolving subspecialty that involves the management of patients with primary or metastatic central and peripheral nervous system neoplasms, as well as any other disorders or complications affecting the nervous system that result either directly or indirectly from central nervous system or systemic malignancies and related treatment. Neurologists serve a critical role in the multidisciplinary management of these complex patients. As leaders of the Child Neurology Society Special Interest Group in NeuroOncology, we propose ways to provide sufficient exposure, minimize knowledge gaps, and optimize training experiences in neuro-oncology for child neurology residency programs. [ABSTRACT FROM AUTHOR]

Neurocutaneous melanosis (NCM) is the condition of abnormal melanocyte deposition in the leptomeninges and brain parenchyma. Associated with congenital melanocytic nevi, NCM can result in neurologic deficits, hydrocephalus, and rarely, malignant transformation of cells. We present the case of a 16‐year‐old boy with NCM who developed malignant leptomeningeal melanoma following immunosuppression with a TNFα inhibitor. To our knowledge, this is the first reported case of a patient with known NCM undergoing malignant transformation after anti‐TNF therapy for inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

ABSTRACTObjective:Our aim was to outline a procedure for obtaining a rapid autopsy in order to collect high-quality postmortem tissue for genomic analysis.Methods: This report details a bi-institutional collaborative effort to coordinate a rapid autopsy for a pediatric patient who had died at home. We discuss the scientific rationale for offering a rapid autopsy to caregivers of pediatric patients as well as parental perspectives on broaching the subject of autopsy. We then review the logistics and coordination involved with planning a rapid autopsy and the sequence of events needed to maximize tissue quality.Results: We report the successful coordination of a rapid autopsy for a patient who died in a hospice setting at her out-of-state home. The time interval from death to the start of the rapid autopsy procedure was 4.5 hours, despite the logistical considerations demanded by the location of the patient. Tumor aliquots and nonneoplastic tissues were successfully snap frozen for downstream genomic studies.Significance Of Results: Physicians should consider trialing a rapid autopsy program at their institution that could be offered to caregivers of pediatric patients. This case report offers a framework to help clinicians develop their own rapid autopsy programs as well as guidelines to help streamline this process for appropriate candidates going forward. [ABSTRACT FROM AUTHOR]

Medulloblastoma (MB) is rare in adults and treatment guidelines are consequently not well-established. Few modern series have reported long-term follow-up and treatment sequelae. We examined long-term outcomes of adult MB patients at one institution. Records of 29 consecutive patients (18 male, 11 female) aged ≥ 18 years who received radiotherapy (RT) for primary MB from 1990 to 2016 were reviewed. Median age at diagnosis was 28 years (range 18-72 years). Seventeen patients were standard risk and 12 were high risk. Nineteen patients had gross total resection, seven had subtotal resection, and three had biopsy only. Median craniospinal irradiation and boost doses were 36 Gy (range 23.4-39.6 Gy) and 55.8 Gy (range 54-59.4 Gy), respectively. Of 24 patients receiving chemotherapy, 20 received concurrent + adjuvant and 4 received adjuvant only. At median follow-up of 9.0 years (range 1.1-20.5 years), five patients recurred: four in the posterior fossa and one in both the posterior fossa and above the tentorium. Five patients died: two of disease progression and three after possible treatment complications (seizure, lobar pneumonia, and multifactorial sepsis). At last follow-up, 23 patients were alive with no evidence of disease. Long-term effects include executive dysfunction (n = 17), weakness/ataxia (n = 16), and depression/anxiety (n = 13). Kaplan-Meier estimates of 10-year overall survival and failure-free survival are 83% (95% confidence interval [CI] 59-93%) and 79% (CI 55-91%), respectively. Despite encouraging disease control in this cohort, long-term sequelae may limit quality of life. Multimodality pediatric regimens using lower RT doses may be considered to reduce treatment-related morbidity. [ABSTRACT FROM AUTHOR]

The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. Twenty-three patients (median age 10 years, range 4–18 years) with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblastoma [n = 2], ependymoma [n = 3]), neuroblastoma (n = 8), Wilms tumor (n = 1), and Ewing sarcoma (n = 1) were treated. Only one DLT occurred (grade 4 hyperuricemia at dose level 4). The most common grade 3 or 4 toxicity at least possibly related to perifosine was neutropenia (8.7%), with the remaining grade 3 or 4 toxicities (fatigue, hyperglycemia, fever, hyperuricemia, and catheter-related infection) occurring in one patient each. Pharmacokinetics was dose-saturable at doses above 50 mg/m2/day with significant inter-patient variability, consistent with findings reported in adult studies. One patient with DIPG (dose level 5) and 4 of 5 patients with high-grade glioma (dose levels 2 and 3) experienced stable disease for two months. Five subjects with neuroblastoma (dose levels 1 through 4) achieved stable disease which was prolonged (≥11 months) in three. No objective responses were noted. In conclusion, the use of perifosine was safe and feasible in patients with recurrent/refractory pediatric CNS and solid tumors. An MTD was not defined by the 5 dose levels investigated. Our RP2D is 50 mg/m2/day. [ABSTRACT FROM AUTHOR]

Neurologists are often consulted for diagnosis and management of neurologic complications in patients undergoing therapy for cancer. Pediatric patients with cancer, often undergoing the same types of therapy as adults with cancer, may experience different adverse events. The set of neurologic complications in children differs from that in adults and the neurologist must take into account the continuing growth and development of the patient as well as significant differences in primary diagnosis across the population. Correctly recognizing complications and initiating prompt treatment may reduce pain and prevent further progression and permanent deficits. Herein, we review the most recent literature on the neurological complications of cancer therapy organized by frequency in the pediatric population. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to investigate the utility and clinical impact of second-opinion interpretations of outside neuroimaging studies by oncologic neuroradiologists at a National Cancer Institute-designated cancer center.Methods: We performed a retrospective analysis of initial outside and second-opinion radiology reports from 300 computed tomography and magnetic resonance imaging studies and identified cases with discrepancies between the two reports. An adult neuro-oncologist, pediatric neuro-oncologist, and head and neck surgeon reviewed each pair of discrepant reports based on their area of expertise, patient age, and the type of study performed. The clinicians were blinded to the origin of each report and recorded whether the differences in the reports would have led to a change in patient management and/or disease staging. Histopathologic analysis, clinical assessment, and/or minimum 3-month imaging follow-up served as the reference standards to establish which of the 2 reports was correct.Results: Among the 283 cases that met our study criteria, there were 55 neuroimaging studies with disagreements (19%) between the initial outside report and second-opinion interpretation. Patient management and/or disease stage would have been altered in 42 of 283 cases (15%) based on report differences as determined by the 2 neuro-oncologists and the surgeon participating in the study. Sufficient follow-up was available in 35 of 42 cases (83%). The second-opinion interpretation was correct 100% of the time (35/35).Conclusion: Second-opinion interpretations of neuroimaging studies by subspecialized oncologic neuroradiologists provide added value by reducing error and optimizing the care of cancer patients. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2708-2714. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Nevocytes (NC) and mastocytes (MC) have different progenitors but share stem cell factor as regulator/ activator of NC and for differentiation/proliferation of MC. Both cell types express stem cell factor receptor CD 117. We hypothesize that large/giant congenital melanocytic nevi (L/GCMN) may associate with MC hyperplasia. Forty-nine L/GCMN were examined, 12 samples from uninvolved skin of L/GCMN patients and 6 control skin samples studied with Giemsa and immunohistochemistry for CD117 and MC-tryptase. Picrosirius red (PR) was used to assess fibrosis. Digital images were used to count MC/mm2 using ImageJ software. Western blot (WB) for MC-tryptase in 12 GCMN and 12 nonnevus samples was performed. Analysis of variance (Tukey) and Pearson statistical tests were applied. Increased MCs were observed in nevus tissue (75.1 ± 35.3 MCs/mm2) and in uninvolved skin (53.74 ± 27.7 MC/ mm2). P = 0.109 from patients with L/GCMN, compared with controls from individuals without L/ GCMN (28.74 ± 8.4 MC/mm2); P = 0.001 supported by results of WB analysis for tryptase. A positive trend toward correlation of MC numbers with fibrosis, assessed by PR staining fell short of statistical significance (r = 0.245; P = 0.086); no difference in fibrosis was found between nevus and non-nevus skin from patients with L/ GCMN (P = 0.136). We found a higher density of MC, both in normal-appearing skin and nevus areas of L/ GCMN patients, compared with control skin samples from individuals without nevi. Given the abnormal wound healing and allergic reactions described in L/GCMN patients, these findings suggest a potential role for MC in the biology of L/GCMN, making them a potential target for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Phantosmia is an infrequently reported and poorly understood qualitative olfactory disorder characterized by the perception of a frequently unpleasant odor in the absence of an odorant stimulus. Peripheral phantosmia is hypothesized to involve abnormally active olfactory receptor neurons while central phantosmia is theorized to be the result of hyperactive neurons in the cortex. The authors present a case report that describes 2 patients with incomparable tumors and radiation fields who both experienced phantosmia featuring a halitosis-like odor during their courses of radiation therapy. Both the 6-year-old with diffuse intrinsic pontine glioma and the 15-year-old with World Health Organization grade II-III astrocytoma in the bifrontal lobes experienced significant distress and decreased quality of life during treatment because of the phantosmia, which resolved after completion of radiation therapy. To the best of the authors’ knowledge, these are the first descriptions of phantosmia during focal or whole-brain radiation therapy. [ABSTRACT FROM AUTHOR]

To test the efficacy and safety of corticotropin-based immunotherapies in pediatric opsoclonus-myoclonus syndrome, 74 children received corticotropin alone or with intravenous immunoglobulin (groups 1 and 2, active controls); or both with rituximab (group 3) or cyclophosphamide (group 4); or with rituximab plus chemotherapy (group 5) or steroid sparers (group 6). There was 65% improvement in motor severity score across groups (P < .0001), but treatment combinations were more effective than corticotropin alone (P = .0009). Groups 3, 4, and 5 responded better than group 1; groups 3 and 5 responded better than group 2. The response frequency to corticotropin was higher than to prior corticosteroids (P < .0001). Fifty-five percent had adverse events (corticosteroid excess), more so with multiagents (P = .03); and 10% had serious adverse events. This study demonstrates greater efficacy of corticotropin-based multimodal therapy compared with conventional therapy, greater response to corticotropin than corticosteroid-based therapy, and overall tolerability. [ABSTRACT FROM AUTHOR]

Meningiomas are among the most common brain tumors in adults. They are most commonly located over the cerebral convexities and are infrequently found in an intraventricular location. Ionizing cranial radiation is a risk factor for late occurrence of meningiomas within the radiation field. While pathologic grading of meningiomas is straightforward, significant variability often exists between pathologists in applying standard grading criteria. This has implications for prognosis. Radiation-induced meningiomas may also have predilection to recur. The authors describe a case of an intraventricular meningioma occurring 23 years after cranial irradiation for childhood acute lymphoblastic leukemia. [ABSTRACT FROM PUBLISHER]