Laser interstitial thermal therapy for pediatric atypical teratoid/rhabdoid tumor: case report.

Herein, the authors describe the successful use of laser interstitial thermal therapy (LITT) for management of metastatic craniospinal disease for biopsy-proven atypical teratoid/rhabdoid tumor in a 16-month-old boy presenting to their care. Specifically, LITT was administered to lesions of the right insula and left caudate. The patient tolerated 2 stages of LITT to the aforementioned lesions without complication and with evidence of radiographic improvement of lesions at the 2- and 6-month follow-up appointments. To the authors' knowledge, this represents the first such published report of LITT for management of atypical teratoid/rhabdoid tumor.

Surgical decision-making in the management of childhood tumors of the CNS disseminated at presentation.

OBJECTIVE It is relatively unusual for pediatric CNS tumors to be disseminated at presentation, and the literature on the clinical features, management, and outcomes of this specific group is scarce. Surgical management in this population is often challenging, particularly in the presence of hydrocephalus. The authors present their recent experience of treating pediatric CNS tumors that were disseminated at presentation, and they compare these lesions with focal tumors. METHODS The authors performed a retrospective review of prospectively collected data on children presenting to a tertiary center between 2003 and 2016 inclusive. RESULTS Of 361 children with CNS tumors, the authors identified 53 patients with disease dissemination at presentation (male/female ratio 34:19, median age 3.8 years, age range 7 days to 15.6 years) and 308 without dissemination at presentation (male/female ratio 161:147, median age 5.8 years, age range 1 day to 16.9 years). Five tumor groups were studied: medulloblastoma (disseminated n = 29, focal n = 74), other primitive neuroectodermal tumor (n = 8, n = 17), atypical teratoid rhabdoid tumor (n = 8, n = 22), pilocytic astrocytoma (n = 6, n = 138), and ependymoma (n = 2, n = 57). The median follow-up duration in survivors was not significantly different between those with disease dissemination at presentation (64.0 months, range 5.2-152.0 months) and those without it (74.5 months, range 4.7-170.1 months) (p > 0.05). When combining data from all 5 tumor groups, dissemination status at presentation was significantly associated with a higher risk of requiring CSF diversion, a higher surgical complication rate, and a reduced likelihood of achieving gross-total resection of the targeted lesion (all variables p < 0.05). Differences between the 5 tumor groups were evident. No factors that predicted the need for permanent CSF diversion following temporary external ventricular drainage were identified on multivariate analysis, and there was no clear superiority of either ventriculoperitoneal shunt surgery or endoscopic third ventriculostomy as a permanent CSF diversion procedure. CONCLUSIONS Tumor type and dissemination status at initial presentation significantly affect outcomes across a range of measures. The management of hydrocephalus in patients with CNS tumors is challenging, and further prospective studies are required to identify the optimal CSF diversion strategy in this population.

Questioning the need for ICU level of care in pediatric patients following elective uncomplicated craniotomy for brain tumors.

OBJECTIVE The object of this study is to address what factors may necessitate the need for intensive care monitoring after elective uncomplicated craniotomy in pediatric patients who are initially managed in a non-intensive care unit setting postoperatively. METHODS A retrospective chart review was undertaken for all patients who underwent elective craniotomy for brain tumor between April of 2007 and April of 2012 and who were directly admitted to the floor postoperatively. Factors such as age, tumor type, craniotomy location, neurological comorbidities, reason for transfer to intensive care unit (ICU) level of care (if applicable), time between admittance to floor and transfer to ICU level of care, and reason for transfer to ICU level of care were assessed. RESULTS Adjusted logistic regression found 2 significant positive predictors of postoperative transfer to the ICU after initial admission to the floor: primitive neuroectodermal tumor pathology (OR 44.10, 95% CI 1.24-1572.16, p = 0.04), and repeat craniotomy during the same hospitalization (OR 13.97, 95% CI 1.21-160.66, p = 0.03). Conversely, 1 negative factor was found: low-grade glioma pathology (OR 0.05, 95% CI 0.00-0.87, p = 0.04). CONCLUSIONS Select pediatric patients may not require ICU level of care after elective uncomplicated pediatric craniotomy. Additional studies are needed to adequately address which patients would benefit from initial ICU admittance following elective craniotomies for brain tumors.

Short-term mortality following surgical procedures for the diagnosis of pediatric brain tumors: outcome analysis in 5533 children from SEER, 2004-2011.

OBJECT Thirty-day mortality is increasingly a reference metric regarding surgical outcomes. Recent data estimate a 30-day mortality rate of 1.4-2.7% after craniotomy for tumors in children. No detailed analysis of short-term mortality following a diagnostic neurosurgical procedure (e.g., resection or tissue biopsy) for tumor in the US pediatric population has been conducted. METHODS The Surveillance, Epidemiology and End Results (SEER) data sets identified patients ≤ 21 years who underwent a diagnostic neurosurgical procedure for primary intracranial tumor from 2004 to 2011. One- and two-month mortality was estimated. Standard statistical methods estimated associations between independent variables and mortality. RESULTS A total of 5533 patients met criteria for inclusion. Death occurred within the calendar month of surgery in 64 patients (1.16%) and by the conclusion of the calendar month following surgery in 95 patients (1.72%). Within the first calendar month, patients < 1 year of age (n = 318) had a risk of death of 5.66%, while those from 1 to 21 years (n = 5215) had a risk of 0.88% (p < 0.0001). By the end of the calendar month following surgery, patients < 1 year (n = 318) had a risk of death of 7.23%, while those from 1 to 21 years (n = 5215) had a risk of 1.38% (p < 0.0001). Children < 1 year at diagnosis were more likely to harbor a high-grade lesion than older children (OR 1.9, 95% CI 1.5-2.4). CONCLUSIONS In the SEER data sets, the risk of death within 30 days of a diagnostic neurosurgical procedure for a primary pediatric brain tumor is between 1.16% and 1.72%, consistent with contemporary data from European populations. The risk of mortality in infants is considerably higher, between 5.66% and 7.23%, and they harbor more aggressive lesions.

Malignant brainstem tumors in children, excluding diffuse intrinsic pontine gliomas.

OBJECT Malignant tumors of the brainstem, excluding classic diffuse intrinsic pontine gliomas (DIPGs), are a very rare, heterogeneous group of neoplasms that have been infrequently described in the literature. In this paper, the authors present their experiences with treating these unique cancers. METHODS A retrospective chart review was conducted to identify eligible cases over a 15-year period. All tumors involving the pons were, by consensus, felt not to be DIPGs based on their neuroimaging features. Demographic information, pathological specimens, neuroimaging characteristics, surgical and nonsurgical management plans, and survival data were gathered for analysis. RESULTS Between January 2000 and December 2014, 29 patients were identified. The mean age at diagnosis was 8.4 years (range 2 months to 25 years), and 17 (59%) patients were male. The most common presenting signs and symptoms were cranial neuropathies (n = 24; 83%), hemiparesis (n = 12; 41%), and ataxia or gait disturbance (n = 10; 34%). There were 18 glial and 11 embryonal tumors. Of the glial tumors, 5 were radiation-induced and 1 was a malignant transformation of a previously known low-grade tumor. Surgical intervention consisted of biopsy alone in 12 patients and some degree of resection in another 15 patients. Two tumors were diagnosed postmortem. The median overall survival for all patients was 196 days (range 15 to 3999 days). There are currently 5 (17%) patients who are still alive: 1 with an anaplastic astrocytoma and the remaining with embryonal tumors. CONCLUSIONS In general, malignant non-DIPG tumors of the brainstem carry a poor prognosis. However, maximal cytoreductive surgery may be an option for select patients with focal tumors. Long-term survival is possible in patients with nonmetastatic embryonal tumors after multimodal treatment, most importantly maximal resection.

The supraorbital eyebrow approach in children: clinical outcomes, cosmetic results, and complications.

OBJECT: The supraorbital eyebrow approach utilizes an eyebrow skin incision to fashion a supraorbital craniotomy for exposure of the subfrontal corridor. This provides anterolateral access to surgical lesions in the anterior cranial fossa, parasellar regions, brainstem, and medial temporal lobe. With use of the endoscope, further areas can be accessed. This approach has been applied effectively in adults, but questions remain about its use in children-specifically with regard to adequate working space, effectiveness for achieving the desired results, cosmesis, and complications. METHODS: The authors conducted a retrospective review of more than 450 cases involving patients of all ages who had undergone a supraorbital eyebrow approach performed by the senior author (C.T.) from 1995 to 2013. Only cases involving patients younger than 18 years with a minimum follow-up of 6 weeks were included in this study. All inpatient and outpatient records were retrospectively reviewed and clinical/operative outcomes, cosmetic results, and complications were recorded. In the present article, the authors briefly describe the surgical approach and highlight any differences in applying it in children. RESULTS: Fifty-four pediatric patients who had undergone a supraorbital eyebrow approach met inclusion criteria. The pathological conditions consisted mostly of tumors or other resectable lesions. In a total of 51 resectable lesions, 44 surgeries resulted in a gross-total (100%) resection and 7 cases resulted in subtotal (50%-99%) resection. The endoscope assisted and expanded visualization or provided access to areas not reached by standard microscopic visualization in all cases. Cosmetic outcomes were excellent. In all cases, the incisional scar was barely visible at 6 weeks. In 3 cases a minor bone defect was observed on the forehead. Given the small size of the frontal sinus in children, no frontal sinus breaches occurred. Additionally, no CSF leak or wound infection was identified. CONCLUSIONS: The supraorbital eyebrow approach is extremely effective in achieving desired results in properly selected cases in patients of all pediatric age ranges, from infants to teenagers. There is sufficient working space for the endoscope and all instruments, allowing for endoscopic assistance and bimanual surgical technique. Cosmetic results are excellent, and complications related to the approach are minimal.

Radiological features of infantile glioblastoma and desmoplastic infantile tumors: British Columbia's Children's Hospital experience.

OBJECT Two of the more common infantile brain tumors, glioblastoma multiforme (GBM) and desmoplastic infantile tumors (DITs), can be difficult to distinguish on MRI. Both tumors occur in the supratentorial compartment and both have solid and cystic components. Differentiating between the 2 on MRI studies could assist the surgeon in discussions with family and child management. The authors report on their institutional experience with both tumors, focusing on radio-graphic features, especially the diffusion studies, which might be useful in distinguishing between infantile GBM and DIT. METHODS A retrospective review was undertaken of all infantile brain tumors treated at British Columbia's Children's Hospital between 1982 and 2012, and cases of GBM and DIT were recorded. Only cases that had imaging were included in the study. A literature review was completed to identify reported cases of infantile GBM and DIT. Only reports that described or included radiological studies (particularly MRI) of the tumors were included. Certain radiographic features of the tumors were reviewed, including location, size, consistency, pattern of enhancement, and features on MR diffusion studies. RESULTS Of 70 cases of infantile brain tumors, 2 GBM cases and 3 DIT cases (all 3 of which were desmoplastic infantile gangliogliomas [DIGs]) met the inclusion criteria. The radiological studies obtained in all 5 cases were reviewed by a neuroradiologist. All 5 patients had supratentorial tumors with cystic-solid consistency. Diffusion MRI studies showed restricted diffusion in the 2 GBM cases, but no evidence of restricted diffusion in the DIG tumors. The GBM tumors were heterogeneously enhancing, and the DIG tumors showed avid and homogeneous enhancement. The literature review revealed 29 cases of infantile GBM and 32 cases of DIG/DIT that met the inclusion criteria. The tumors were large in both groups. The tumors were cystic-solid in consistency in 10 of 30 (33%) of GBM cases and 28 of 32 (87.5%) of DIT cases. The contrast enhancement was heterogeneous in 9 of 30 (30%) GBM cases, and it was homogeneous and avid in 27 of 32 (84%) of DIT cases. Diffusion studies were recorded in 2 published infantile GBM cases, and in both of them diffusion was restricted. The authors only found 1 report that discussed DIG tumor features on MR diffusion studies, but the interpretation was difficult and unclear. CONCLUSIONS Magnetic resonance imaging, especially diffusion-weighted imaging, may be a useful aid in distinguishing between infantile GBM and DIT tumors, with infantile GBM demonstrating restricted diffusion.

Neoadjuvant chemotherapy for brain tumors in infants and young children.

OBJECT: Because of their large size and high vascularity, complete removal of brain tumors in infants and young children is often difficult. In most cases the degree of resection is associated with prognosis. Neoadjuvant chemotherapy may facilitate resection by reducing the vascularity of the tumor. The authors evaluated the effectiveness of neoadjuvant chemotherapy in the management of these tumors. METHODS: The authors performed a retrospective review of infants and young children who underwent tumor removal after neoadjuvant chemotherapy. RESULTS: Nine consecutive patients underwent resection after neoadjuvant chemotherapy during the period February 2004 to December 2012. The mean age at diagnosis was 18 months (range 2-50 months). The average largest tumor diameter was 71 mm (range 30-130 mm) at initial surgery. Five patients underwent partial resection, and 4 underwent biopsy as the initial surgery. The histopathological diagnoses were ependymoma in 2 patients, anaplastic ependymoma in 1, primitive neuroectodermal tumor (PNET) in 2, choroid plexus carcinoma in 1, atypical teratoid/rhabdoid tumor (AT/RT) in 1, glioblastoma in 1, and embryonal tumor with abundant neuropil and true rosettes in 1. After 2-4 courses of multiagent chemotherapy (mainly with vincristine, cyclophosphamide, etoposide, and cisplatin), the second-look surgery was performed. In 1 patient with a PNET, intratumoral hemorrhage was observed after 2 courses of chemotherapy. The mean interval between the initial and the second-look surgery was 3 months. The tumor volume was reduced to varying degrees in 5 patients (56%) after chemotherapy. Intraoperatively, the vascularity of the tumor was considerably reduced, and the tumor was more circumscribed in all cases. Gross-total resection was achieved in 8 patients (89%) and neartotal resection in 1 (11%). Histopathological examination demonstrated fibrotic tissue circumscribing the tumor in 6 of 9 cases (67%). The average blood loss was 20% of the estimated blood volume, and 3 patients (33%) required a blood transfusion. There was no surgical mortality. One patient had transient dysphasia postoperatively. The mean follow-up period was 28 months. At the last follow-up, 2 patients (22%) had died (1 died of tumor progression and 1 of sepsis), and 4 patients (44%) had no tumor recurrence. CONCLUSIONS: Neoadjuvant chemotherapy for brain tumors in infants and young children was effective in reduction of tumor vascularity and clarification of the tumor-brain interface, which significantly facilitated maximal tumor resection.

Embryonal tumor with multilayered rosettes of the fourth ventricle: case report.

Embryonal tumor with multilayered rosettes (ETMR) is a recently described pathological entity. These primitive central nervous system tumors harbor amplification of the 19q13.42 locus and resultant overexpression of the LIN28A protein. Although the WHO currently recognizes 3 distinct histopathological entities-embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma-recent studies indicate that these tumors have a common molecular profile and clinical course and that they are now classified as a single entity. Here the authors present a case of ETMR located in the fourth ventricle in a 12-month-old boy. The histopathology featured areas of neuropil-like stroma and highly cellular foci with characteristic multilayered rosettes. The authors discuss the clinical, radiological, and histopathological findings in this case and compare them with data in previously published cases in the literature. A review of studies assessing the molecular mechanisms underlying these tumors is also presented.

The pathological spectrum of solid CNS metastases in the pediatric population.

OBJECT: Collectively, metastatic tumors are the most common malignancy encountered in the adult central nervous system (CNS), arising most often from lung, breast, skin, and gastrointestinal tract carcinomas. Limited information is available in the literature regarding solid nonhematopoietic CNS metastases in children. The authors carried out a retrospective study of pediatric metastatic neoplasms to the CNS treated in a 30-year period to characterize their frequency, common histological subtypes, and sites of origin. METHODS: The archival pathology files were searched (1981-2011) for metastatic tumors to the CNS in patients 21 years of age and younger. Pathology material was reviewed, tumors were classified by site of origin and histological subtype, and survival was evaluated. RESULTS: The authors identified 26 patients with solid nonhematopoietic CNS metastases out of 1135 pediatric CNS tumors diagnosed from 1981 to 2011. Patients ranged in age from 1.5 to 20.3 years and were equally divided between sexes. Most CNS metastases were supratentorial (85%) and solitary (65%). The mean interval from primary malignant diagnosis to CNS metastasis was 27 months. Sites of origin included kidney/adrenal, bone/soft tissue, gonads, head and neck, lung, and liver. Mean survival after CNS involvement was 36.6 months. Overall 1-year and 5-year survival rates were 52% and 16%, respectively. CONCLUSIONS: In neuropathology practice, nonhematopoietic pediatric CNS metastases are far less common than are nonhematopoietic adult CNS metastases, accounting for approximately 2% of all pediatric CNS tumors. The most common tumors to exhibit CNS metastasis are of kidney/adrenal origin, followed by those from bone/soft tissue. As expected, prognosis is dismal, despite aggressive therapy.

Ependymoblastoma with cystic change in a child.

Ependymoblastoma is a rare and devastating primitive neuroectodermal tumor with ependymal differentiation. This tumor occurs very early in life and shows rapid growth and a diffuse infiltration through the leptomeningeal space. This neoplasm is characterized by uniform neuroepithelial cells, multilayered ependymal rosettes, perivascular pseudorosettes, and numerous mitotic figures. In this article, the authors report on a 4-year-old girl who was diagnosed as having an ependymoblastoma with cystic change. After a series of laboratory and imaging examinations, the left frontal solid-cystic lesion was surgically excised. Histological examinations confirmed the diagnosis of ependymoblastoma. The patient's intracranial hypertension symptoms were alleviated, and postoperative chemotherapy was performed. At the 6-month follow-up visit, MRI demonstrated evidence of relapse, and the girl died of tumor recurrence 14 months after surgery. Databases (PubMed, MEDLINE, Embase, and Web of Science) were searched for relevant articles published from 1970 to 2012; 71 eligible cases of ependymoblastoma were obtained, and 42 provided complete clinical details. Prognosis of children with ependymoblastoma is poor, and data on clinical behavior and optimal treatment strategies are lacking, but sustained remissions have been achieved after multimodal treatment according to existing literature. In this report, the clinical and histopathological features and therapeutic options of this tumor are discussed in the light of the published data. Further studies, especially those examining multimodality therapy, are needed to improve survival of children with this rare malignant CNS tumor.

Initial diagnosis of the congenital disorder of glycosylation PMM2-CDG (CDG1a) in a 4-year-old girl after neurosurgical intervention for cerebral hemorrhage.

The congenital disorder of glycosylation characterized by a deficiency of phosphomannomutase 2 (PMM2-CDG) is the most common variant of congenital disorders of glycosylation. Besides typical clinical features, such as dysmorphism and abnormal body fat distribution, coagulation abnormities often lead to thromboembolic and hemorrhagic events in these patients. However, only 2 cases of intracerebral bleeding in patients with PMM2-CDG have been described so far. A 4-year-old girl who initially presented with symptoms resulting from raised intracranial pressure underwent acute neurosurgical intervention for intracranial hemorrhage. The differential diagnoses after MRI included arteriovenous malformation and intraparenchymal brain tumor. However, clinical investigations promoted the diagnosis of PMM2-CDG, which was supported further by neuropathological findings and finally confirmed by isoelectric focusing and mutational analysis. No major complications or neurological deficits were evident after surgery, and the patient was able to attend an integrated kindergarten. Unexplained intracranial hemorrhage should raise suspicion of a metabolic disorder and should be discussed with specialists to rule out an orphan disease such as PMM2-CDG.

Cerebrospinal fluid disturbances after 381 consecutive craniotomies for intracranial tumors in pediatric patients.

OBJECT: The aim of this study was to investigate the incidence of CSF disturbances before and after intracranial surgery for pediatric brain tumors in a large, contemporary, single-institution consecutive series. METHODS: All pediatric patients (those < 18 years old), from a well-defined population of 3.0 million inhabitants, who underwent craniotomies for intracranial tumors at Oslo University Hospital in Rikshospitalet between 2000 and 2010 were included. The patients were identified from the authors' prospectively collected database. A thorough review of all medical charts was performed to validate all the database data. RESULTS: Included in the study were 381 consecutive craniotomies, performed on 302 patients (50.1% male, 49.9% female). The mean age of the patients in the study was 8.63 years (range 0-17.98 years). The follow-up rate was 100%. Primary craniotomies were performed in 282 cases (74%), while 99 cases (26%) were secondary craniotomies. Tumors were located supratentorially in 249 cases (65.3%), in the posterior fossa in 105 (27.6%), and in the brainstem/diencephalon in 27 (7.1%). The surgical approach was supratentorial in 260 cases (68.2%) and infratentorial in 121 (31.8%). Preoperative hydrocephalus was found in 124 cases (32.5%), and 71 (86.6%) of 82 achieved complete cure with tumor resection only. New-onset postoperative hydrocephalus was observed in 9 (3.5%) of 257 cases. The rate of postoperative CSF leaks was 6.3%. CONCLUSIONS: Preoperative hydrocephalus was found in 32.5% of pediatric patients with brain tumors treated using craniotomies. Tumor resection alone cured preoperative hydrocephalus in 86.6% of cases and the incidence of new-onset hydrocephalus after craniotomy was only 3.5%.