Faculty Bibliography

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare, benign, congenital tumor of the dermis and subcutaneous tissue comprised of skeletal muscle and adipose and adnexal elements. Although the majority of cases are an incidental finding in otherwise healthy patients, some have been reported in association with other anomalies. We present a full-term boy evaluated on day 2 of life for two lesions located on the midline of the lower back and right buttock that each appeared clinically as an atrophic, pink plaque. Ultrasound of the midline lesion revealed an underlying lipomyelomeningocele with a tethered cord in the spinal canal. Histopathology of the right buttock cutaneous lesion was consistent with a diagnosis of RMH. Surgical excision was performed on the midline intradural lipoma and the lesion on the buttock was monitored clinically. Repeat biopsy of this site at 1 year of age revealed complete spontaneous regression. This case highlights three interesting features: the association with an occult spinal dysraphism lipomyelomeningocele and tethered cord, the clinical presentation of an atrophic plaque as opposed to the more commonly reported raised lesions, and the phenomenon of spontaneous regression of the lesion. Most importantly, this final feature of regression in our patient suggests that, in the absence of symptoms, clinical observation of RMH lesions is warranted for spontaneous regression for 1 to 2 years provided that no functional deficit is noted and that the cutaneous or deeper lesions are not causing a medical problem.

Learning Objectives: The purpose of this study was to identify trends in postoperative transfusion practice in children undergoing cranial vault reconstruction. We hypothesize that young age is a risk factors for blood product transfusion requirement. Methods: A retrospective chart review was performed for all patients undergoing fronto-orbital advancement or cranial vault reconstruction at a single, medium-sized, academic tertiary pediatric hospital from June 14, 2011 to June 4, 2014. Diagnosis, procedure type, age, postoperative transfusion, hemoglobin level, platelet count, and international normalized ratio (INR) were recorded. Results: 90 patients were included in the analysis. Patient's age in months (mo) and years (yrs) ranged from 2 mo to 16 yrs. 25 patients (28%) were transfused with packed red blood cells (pRBC) and 4 patients (4%) were transfused with fresh frozen plasma (FFP). Median age of the total population was 0.8 yrs. Median age of patients receiving pRBC, FFP, and no transfusions were 0.7, 0.9, and 0.8 yrs, respectively. There may have been a trend toward younger age in patients that received pRBC transfusion when compared to patients receiving no transfusion (median 0.7 vs 0.8, p = 0.12, Wilcoxon rank-sum test). The hemoglobin nadir was 5.2 g/dL and 6 g/dL for patients who were transfused and who were not transfused with pRBCs, respectively. The mean hemoglobin level indicating need for pRBC transfusion was 6.85 + 1.07 g/dL and the mean INR indicating need for FFP transfusion was 1.38 + 0.05. Conclusions: This observational study of pediatric patients undergoing cranial vault reconstruction shows a trend that patients receiving postoperative pRBC transfusions were younger than patients that were not transfused. Further studies are needed to assess what impact age, hemoglobin nadir, and receipt of transfusion in the postoperative period has on short- and long-term postoperative outcomes

BACKGROUND: Activation of the RAS-RAF-MEK-ERK signaling pathway is thought to be the key driver of pediatric low-grade astrocytoma (PLGA) growth. Sorafenib is a multikinase inhibitor targeting BRAF, VEGFR, PDGFR, and c-kit. This multicenter phase II study was conducted to determine the response rate to sorafenib in patients with recurrent or progressive PLGA. METHODS: Key eligibility criteria included age >/=2 years, progressive PLGA evaluable on MRI, and at least one prior chemotherapy treatment. Sorafenib was administered twice daily at 200 mg/m2/dose (maximum of 400 mg/dose) in continuous 28-day cycles. MRI, including 3-dimensional volumetric tumor analysis, was performed every 12 weeks. BRAF molecular testing was performed on tumor tissue when available. RESULTS: Eleven patients, including 3 with neurofibromatosis type 1 (NF1), were evaluable for response; 5 tested positive for BRAF duplication. Nine patients (82%) came off trial due to radiological tumor progression after 2 or 3 cycles, including 3 patients with confirmed BRAF duplication. Median time to progression was 2.8 months (95% CI, 2.1-31.0 months). Enrollment was terminated early due to this rapid and unexpectedly high progression rate. Tumor tissue obtained from 4 patients after termination of the study showed viable pilocytic or pilomyxoid astrocytoma. CONCLUSIONS: Sorafenib produced unexpected and unprecedented acceleration of tumor growth in children with PLGA, irrespective of NF1 or tumor BRAF status. In vitro studies with sorafenib indicate that this effect is likely related to paradoxical ERK activation. Close monitoring for early tumor progression should be included in trials of novel agents that modulate signal transduction.

Evidence suggests that normal pressure hydrocephalus (NPH) is underdiagnosed in day to day radiologic practice, and differentiating NPH from cerebral atrophy due to other neurodegenerative diseases and normal aging remains a challenge. To better characterize NPH, we test the hypothesis that a prediction model based on automated MRI brain tissue segmentation can help differentiate shunt-responsive NPH patients from cerebral atrophy due to Alzheimer disease (AD) and normal aging. Brain segmentation into gray and white matter (GM, WM), and intracranial cerebrospinal fluid was derived from pre-shunt T1-weighted MRI of 15 shunt-responsive NPH patients (9 men, 72.6 +/- 8.0 years-old), 17 AD patients (10 men, 72.1 +/- 11.0 years-old) chosen as a representative of cerebral atrophy in this age group; and 18 matched healthy elderly controls (HC, 7 men, 69.7 +/- 7.0 years old). A multinomial prediction model was generated based on brain tissue volume distributions. GM decrease of 33 % relative to HC characterized AD (P < 0.005). High preoperative ventricular and near normal GM volumes characterized NPH. A multinomial regression model based on gender, GM and ventricular volume had 96.3 % accuracy differentiating NPH from AD and HC. In conclusion, automated MRI brain tissue segmentation differentiates shunt-responsive NPH with high accuracy from atrophy due to AD and normal aging. This method may improve diagnosis of NPH and improve our ability to distinguish normal from pathologic aging.