Rosette-Forming Glioneuronal Tumor of the Fourth Ventricle in Children: Case Report and Literature Review.

BACKGROUND: Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a rare World Health Organization (WHO) grade I neoplasm. Gross total resection (GTR) is the treatment of choice, and there is no firm evidence supporting other treatment options when GTR is not feasible. CASE DESCRIPTION: We report a 6-year-old boy who, following an initial subtotal resection of a fourth ventricular RGNT, received an individualized chemotherapy protocol with vincristine, etoposide, and carboplatin for 3 cycles. The tumor was stable for 2 years after the completion of chemotherapy but then began to progress, at which point GTR was successfully performed. In addition, we completed a comprehensive literature review of RGNT cases. To date, a total of 104 cases have been reported, 33 of which are pediatric cases. Recurrence has been reported in only 7 cases of all ages (4 in the pediatric population). Radiotherapy has been used in several cases, but adjuvant chemotherapy has been reported only once following a recurrence. CONCLUSIONS: We report a case of chemotherapy administration as a first-line treatment for a subtotally resected RGNT. Chemotherapy may be considered as an adjuvant therapy option for RGNT when GTR cannot be achieved. Furthermore, increased incidence of recurrence in the pediatric population may suggest that the tumor biology of RGNT in children differs from that in adults.

Pitfalls of Neuroendoscopic Biopsy of Intraventricular Germ Cell Tumors.

OBJECTIVE: A neuroendoscopic biopsy has become common for the diagnosis of ventricular tumors. However, its utility in patients with germ cell tumors (GCTs) has not been well discussed. We examined the usefulness and pitfalls of neuroendoscopic biopsies of intraventricular GCTs at a single institution. METHODS: We retrospectively studied 21 consecutive patients diagnosed with GCTs by a neuroendoscopic biopsy of the ventricular region via the lateral ventricle. We examined the localization of tumors, histologic diagnoses using biopsies, surgical complications, and consistency of the diagnosis at the latest follow-up. RESULTS: Tumor specimens were obtained from a pineal lesion (n = 20), neurohypophysial lesion (n = 5), and lateral ventricular wall lesion (n = 2). In 5 patients, the specimens were obtained from multiple areas. The initial diagnoses were pure germinoma (n = 16), immature teratoma (n = 1), yolk sac tumor (n = 1), and mixed GCT (n = 3). Six of 21 patients needed a second transcranial removal of enhanced residual lesions in the course of the treatment. A discrepancy in the histologic diagnosis between 2 surgeries occurred in 3 patients: All 3 patients had a new diagnosis of teratoma component following transcranial surgery. No postoperative mortality or permanent morbidity related to the neuroendoscopic procedures was noted. CONCLUSION: Neuroendoscopic biopsies are safe and useful for obtaining reliable histologic diagnoses in the management of GCTs. However, for GCTs with mixed histology, biopsies are susceptible to diagnostic errors, especially missing detecting a component of teratoma.

Intraventricular Gliosarcomas: Literature Review and a Case Description.

OBJECTIVE: Gliosarcomas are rare, extremely high-grade, bimorphous malignant tumors of the central nervous system. Intraventricular location is extremely rare, and only a few case reports exist in the literature. The aim of our study is to review clinical, radiologic, and pathologic features of this unique oncological entity and report this rare case of primary cystic intraventricular gliosarcoma (IVGS) with a mural nodule. METHODS: A 23-year-old man had a 6-month history of headache and a single episode of generalized seizure. Examination revealed grade 1 papilledema. Brain magnetic resonance imaging revealed a cystic lesion with a mural nodule located within the occipital horn of the right lateral ventricle, which exhibited an intense enhancement of the nodule with patchy rim enhancement of the wall on gadolinium administration. The patient underwent right parietal craniotomy and gross total excision of the tumor. RESULTS: Postoperative computed tomography of the brain showed evidence of complete tumor excision. The postoperative course of the patient was uneventful. Histopathologic analysis revealed malignant tumor comprising both glial and mesenchymal components suggestive of gliosarcoma. CONCLUSION: Primary IVGS is an extremely rare malignancy, with only 9 cases reported in the literature, and it should be considered in the differential diagnosis of lateral ventricular tumors.

Methotrexate administration directly into the fourth ventricle in children with malignant fourth ventricular brain tumors: a pilot clinical trial.

We hypothesize that chemotherapy can be safely administered directly into the fourth ventricle to treat recurrent malignant brain tumors in children. For the first time in humans, methotrexate was infused into the fourth ventricle in children with recurrent, malignant brain tumors. A catheter was surgically placed into the fourth ventricle and attached to a ventricular access device. Cerebrospinal fluid (CSF) flow was confirmed by CINE MRI postoperatively. Each cycle consisted of 4 consecutive daily methotrexate infusions (2 milligrams). Disease response was monitored with serial MRI scans and CSF cytologic analysis. Trough CSF methotrexate levels were sampled. Five patients (3 with medulloblastoma and 2 with ependymoma) received 18, 18, 12, 9, and 3 cycles, respectively. There were no serious adverse events or new neurological deficits attributed to methotrexate. Two additional enrolled patients were withdrawn prior to planned infusions due to rapid disease progression. Median serum methotrexate level 4 h after infusion was 0.04 µmol/L. Range was 0.02-0.13 µmol/L. Median trough CSF methotrexate level 24 h after infusion was 3.18 µmol/L (range 0.53-212.36 µmol/L). All three patients with medulloblastoma had partial response or stable disease until one patient had progressive disease after cycle 18. Both patients with ependymoma had progressive disease after 9 and 3 cycles, respectively. Low-dose methotrexate can be infused into the fourth ventricle without causing neurological toxicity. Some patients with recurrent medulloblastoma experience a beneficial anti-tumor effect both within the fourth ventricle and at distant sites.

Análisis coste-efectividad de la cirugía del glioma maligno guiada por fluorescencia con ácido 5-aminolevulínico / Cost-effectiveness of 5-aminolevulinic acid-induced fluorescence in malignant glioma surgery

Objetivo: Evaluar el coste-efectividad del ácido 5-aminolevulínico (5-ALA, Gliolan(R)) en pacientes intervenidos quirúrgicamente de glioma maligno, en condiciones de práctica médica habitual en España. Material y métodos: Se determinaron las ratios de coste incremental por resección completa (RC) y de coste incremental por año de vida ajustado por calidad (AVAC) ganado, sobre la base de los datos recogidos en el estudio observacional VISIONA. Resultados. El coste incremental con 5-ALA frente a la cirugía convencional con luz blanca asciende a 4.550 Euros por RC adicional conseguida y a 9.021 Euros por AVAC ganado. Estos resultados se muestran consistentes en un análisis de sensibilidad. Conclusión: La cirugía del glioma maligno guiada por fluorescencia con 5-ALA conlleva un incremento de costes moderado respecto a la práctica quirúrgica actual y muestra una relación coste-efectividad favorable

Objective: This study evaluates the cost-effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan®) in patients undergoing surgery for malignant glioma, in standard clinical practice conditions in Spain. Material and methods: Cost-effectiveness ratios were determined in terms of incremental cost per complete resection (CR) and incremental cost per additional quality-adjusted life year (QALY), based on data collected in the VISIONA observational study. Results: Incremental cost with 5-ALA versus conventional surgery using white light only amounts to Euros 4550 per additional CR achieved and Euros 9021 per QALY gained. A sensitivity analysis shows these results to be robust. Conclusion: Malignant glioma surgery guided by 5-ALA fluorescence entails a moderate increase in hospital costs compared to current surgical practice and can be considered a cost-effective innovation

Use of mTOR inhibitor everolimus in three neonates for treatment of tumors associated with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex is characterized by the growth of benign tumors in multiple organs, caused by the disinhibition of the mammalian target of rapamycin (mTOR) protein. mTOR inhibitors, such as everolimus, are used in patients with tuberous sclerosis complex, mainly to reduce the size of renal angiomyolipomas and subependymal giant cell astrocytomas. There are minimal data available regarding its use during the neonatal period. METHODS: We report clinical and pharmacological data of three neonates treated with the mTOR inhibitor everolimus (two hemodynamically significant cardiac rhabdomyomas and one voluminous subependymal giant cell astrocytoma). RESULTS: Beneficial clinical responses were observed in all three patients and the medication was generally well-tolerated. Optimal dose was 0.1 mg orally once daily and was confirmed with therapeutic drug monitoring. CONCLUSION: Everolimus is a promising pharmacological approach to treat clinically significant inoperable cardiac rhabdomyomas or subependymal giant cell astrocytoma associated with tuberous sclerosis complex during the neonatal period.

Persistent communicating hydrocephalus in adult tuberous sclerosis patients: a possible therapeutic role for everolimus.

Subependymal giant cell tumor (SGCT) is a benign intraventricular tumor, usually located near the foramen of Monro. It is almost always associated with tuberous sclerosis complex (TSC). SGCTs may obstruct cerebrospinal fluid (CSF) pathways. Rarely, they may secrete a protein-rich exudate, causing communicating hydrocephalus. Surgery is indicated for symptomatic lesions or growing asymptomatic lesions. The operative approach to SGCT has shifted from simple shunt placement to a more aggressive approach, leading to early attempts at gross total resection. Recently, the mTOR inhibitor everolimus has been approved for treating SGCT. In this article, we present two cases of recurrent shunt malfunctions in adult TSC patients with protein-secreting SGCTs. We describe the complexity of treating such patients with an emphasis on the role mTOR inhibitors may have in their management. We also review the literature on surgical management of SGCT-related hydrocephalus.

[A case of intraventricular dissemination arising from hepatocelullar carcinoma effectively treated with intrathecal administration of methotrexate].

A 78-year-old man with hepatocellular carcinoma was admitted to our hospital for vertigo after transcatheter arterial chemoembolization. Contrast-enhanced magnetic resonance imaging revealed metastasis in the cerebellar vermis. Although the cerebellar metastasis decreased in size after cyberknife radiotherapy, multiple enhancing nodules appeared in the cerebral ventricles. A diagnosis of intraventricular dissemination from the cerebellar metastatic lesion originating from the hepatocellular carcinoma was made. Six intrathecal administrations of 20 mg of methotrexate through lumbar puncture resulted in a dramatic decrease in the intraventricular dissemination. Although intraventricular dissemination recurred 4 months later, these lesions disappeared after an additional 8 administrations of intrathecal methotrexate. Intraventricular dissemination arising from hepatocellular carcinoma is rare. Here we report a case that was successfully treated by intrathecal chemotherapy with methotrexate.

Microdialysis measurement of intratumoral temozolomide concentration after cediranib, a pan-VEGF receptor tyrosine kinase inhibitor, in a U87 glioma model.

BACKGROUND: Combining anti-angiogenesis agents with cytotoxic agents for the treatment of malignant gliomas may affect the cytotoxic drug distribution by normalizing the blood-brain barrier (BBB). This study examines the intratumoral concentration of temozolomide (TMZ) in the presence and absence of the pan-VEGF receptor tyrosine kinase inhibitor, cediranib. METHODS: Seven nude rats bearing U87 intracerebral gliomas had a microdialysis probe centered within the tumor. Ten-days after tumor implantation, TMZ (50 mg/kg) was given orally. The extracellular fluid (ECF) concentrations of TMZ within the tumor were assessed via microdialysis for 6 h following TMZ administration. Cediranib (6 mg/kg) was then given orally, and 12 h later, TMZ was re-administered with subsequent microdialysis collection. A subset of animals also underwent functional MRI to assess angiogenesis in vivo at post-inoculation days 12 and 21, before and after the cediranib treatment. RESULTS: After dosing of oral TMZ only, ECF-TMZ mean-C(max) and area under the concentration curve(AUC(0-∞)) within the tumor were 0.59 µg/mL and 1.82 µg h/mL, respectively. Post-cediranib, ECF-TMZ mean-C(max) and AUC(0-∞) were 0.83 µg/mL and 3.72 ± 0.61 µg h/mL within the tumor, respectively. This represented a 1.4-fold (p = 0.3) and 2.0-fold (p = 0.06) increase in the ECF-TMZ C(max) and AUC(0-∞), respectively, after cediranib administration. In vivo MRI measurements of the various vascular parameters were consistent with a BBB "normalization" profile following cediranib treatment. CONCLUSIONS: In the U87 intracerebral glioma model, within the first day of administration of cediranib, the intratumoral concentrations of TMZ in tumor ECF were slightly, but not statistically significantly, increased when compared to the treatment of TMZ alone with radiographic evidence of a normalized BBB.

Effective everolimus treatment of inoperable, life-threatening subependymal giant cell astrocytoma and intractable epilepsy in a patient with tuberous sclerosis complex.

We present successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with tuberous sclerosis complex. The patient underwent several partial tumor resections complicated by intraoperative cardiac arrest. The tumor has been regrowing and produced severe clinical symptoms. Everolimus treatment resulted in marked tumor regression, significant improvement in patient's ambulation and cessation of seizures. Moreover, the therapy was well tolerated. These findings indicate that everolimus treatment should be considered as a therapeutic option alternative to surgery in patients with tuberous sclerosis complex.

Diffuse central neurocytoma with craniospinal dissemination.

Central neurocytomas (CN) are benign central nervous system (CNS) tumors of neuroglial origin that represent 0.25 to 0.5% of all intracranial tumors in adults and an even smaller proportion of pediatric CNS tumors. These tumors characteristically occur in the subependymal layer of the lateral ventricle near the foramen of Monro and appear as sharply demarcated, solitary lesions. Surgical resection is considered curative, as the reported recurrence rate is less than 5% for patients with localized disease. In this report, we describe the case of a three-year-old boy with a diffuse CN with craniospinal dissemination identified at the time of diagnosis. Given the extensive nature of the disease, surgical resection was not indicated and he underwent a chemotherapeutic regimen of vincristine and carboplatin. At 18 months followup, the patient has completed 6 of 8 total cycles of vincristine and carboplatin and serial imaging shows stable disease within the craniospinal axis.

Pediatric cerebellar pilomyxoid-spectrum astrocytomas.

OBJECT: Pediatric cerebellar astrocytomas with pilomyxoid features include classic pilomyxoid astrocytomas (PMAs) and intermediate pilomyxoid tumors (IPTs). Since the original description of PMA in 1999, most reports in the literature have described PMAs arising from the hypothalamic/chiasmatic region. To the authors' knowledge, PMAs arising from the posterior fossa have not been discussed in the neurosurgical literature. Intermediate pilomyxoid tumors, or tumors with pathological features of both pilocytic astrocytoma (PA) and PMA, have only recently been described. In this article, the authors present 2 cases that fall within the spectrum of pediatric cerebellar PMA-including a classic PMA and an intermediate pilomyxoid tumor. The authors compare the radiological presentation, surgical results, and postoperative course to findings in a cohort of 15 patients with cerebellar PAs. METHODS: Between 2003 and 2010, 2 patients with pilomyxoid-spectrum astrocytomas underwent treatment at Vanderbilt Children's Hospital. One was a 22-month-old girl who presented with progressive gait disturbance and falls. The other was a 4-year-old girl who presented with ataxia and generalized weakness. In a retrospective review of pediatric cerebellar neoplasms resected by the senior author during this period, these tumors comprised 4% of cerebellar neoplasms and approximately 10% of cerebellar glial neoplasms. RESULTS: Both patients were treated with midline suboccipital craniotomy for resection. In both cases, tumor invasion anteriorly into the brainstem prevented gross-total resection. the patient in Case 1 was placed on chemotherapy following pathological diagnosis and later developed definitive evidence of leptomeningeal dissemination (LD) 3 years after the operation. The patient in Case 2 was placed on chemotherapy after exhibiting progressive evidence of local recurrence (findings were negative for LD) 12 months following resection. CONCLUSIONS: Pediatric patients with cerebellar pilomyxoid-spectrum astrocytomas appear to suffer higher rates of local recurrence and LD than pediatric patients with cerebellar PAs.

Occlusion of surgical opening of the ventricular system with fibrinogen-coated collagen fleece: a case collection study.

BACKGROUND: Implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafer for malignant glioma is not recommended in the case of surgical opening of the ventricular system during microsurgical tumor resection because the wafer material may dislocate from the resection cavity into the ventricular system and cause obstructive hydrocephalus. TachoSil is an adhesive collagen fleece used in different surgical disciplines that provides an air- and liquid-tight seal closing communications between the ventricular system and the resection cavity after tumor removal. METHODS: Occlusion of ventricular defects with TachoSil after microsurgical glioma resection was performed in two patients with newly diagnosed and seven patients with recurrent malignant glioma prior to BCNU wafer implantation into the resection cavity. Early postoperative cranial computed tomography (CCT)/MRI and follow-up MRI at 3 months' intervals were performed with a median follow-up of 10.4 months. RESULTS: The collagen fleece was identified as a linear structure hypodense/hypointense to white matter on postoperative CT/MRI separating the resection cavity from the ventricular lumen in all cases. In no case did early CCT/MRI or follow-up MRI reveal wafer material within the ventricular system. In no case did signs of obstructive hydrocephalus occur. CONCLUSION: Sealing of the ventricular system using a fibrinogen-coated collagen fleece effectively separates the resection cavity from the ventricular system and allows implantation of BCNU wafers into the resection cavity. No morphological evidence for wafer material dislocation into the ventricular system or obstruction of CSF pathways was found in nine patients who received 41 follow-up MRI over 10.4 months of follow-up.

Subarachnoid dissemination of intraventricular tumors following simultaneous endoscopic biopsy and third ventriculostomy.

OBJECT: Endoscopic biopsy with concomitant third ventriculostomy (ETV) is a well-established diagnostic and therapeutic maneuver in patients presenting with noncommunicating hydrocephalus resulting from a tumor of the pineal region or posterior third ventricle. Fenestration of the floor of the third ventricle theoretically provides a conduit for the subarachnoid dissemination of an intraventricular tumor. The aim of this study was to ascertain the rate of leptomeningeal dissemination following this surgical procedure. METHODS: The authors conducted a review of all patients for whom an ETV and simultaneous endoscopic biopsy procedure or tumor resection had been performed at their institutions between 1995 and 2008. Patients were divided into high or low risk groups by leptomeningeal metastatic potential based on pathology. All available postoperative clinical and radiographic data, including MR imaging of the brain and spinal cord, as well as CSF sampling were evaluated when available. A review of the literature was then conducted to establish rates of distant leptomeningeal dissemination for comparative purposes. RESULTS: Thirty-two patients satisfied the criteria for study inclusion. Pathology revealed that 22 had a high risk for leptomeningeal dissemination. New leptomeningeal disease (1 yolk sac tumor and 1 pineoblastoma) occurred in 2 patients. The median clinical and brain MR imaging follow-ups overall were 34 (range 2-103 months) and 38 months (range 1-94 months), respectively. Follow-up MR imaging of the spine was performed in 12 patients (median 7 months postoperation), and CSF was analyzed in 15 patients (median 1 month postoperation). A Kaplan-Meier survival analysis predicted a 2-year metastasis-free survival of 94.7% for high-risk patients. Baseline rates of dissemination when ETV was not performed were in general between 8 and 24% for various high-risk pathologies according to a literature review. CONCLUSIONS: The rate of leptomeningeal metastasis of tumors in this biopsy and ETV study was not increased when compared with rates from large series in the literature.

Intrathecal chemotherapy delivered by a lumbar-thecal catheter in metastatic medulloblastoma: a case illustration.

BACKGROUND: Medulloblastoma is the most common malignant brain tumour in children. Despite recent advances, the prognosis in high risk patients remains poor. Further improvement in survival is dependent upon the development of strategies to attack the tumour more effectively, but with less toxicity. Intrathecal chemotherapy, is an ideal but currently underused method of directly targeting residual tumour within the area of resection and the leptomeningeal disease commonly associated with this tumour. METHOD: We describe the case of a 12 yr old child with metastatic medulloblastoma, who received intrathecal topotecan via a spinal catheter. CONCLUSION: This method represents a simple, safe and effective method of delivering an even and widespread distribution of drug within the cerebrospinal fluid (CSF) of the neuroaxis. With new agents being identified and others in the early stages of development, intrathecal chemotherapy may emerge as an important therapeutic option to consider when faced with such challenging cases.

Acute transient encephalopathy following paclitaxel treatment in an adolescent with a recurrent suprasellar germinoma.

Paclitaxel is an antineoplastic agent that is used in the treatment of a variety of solid tumors. Dose-limiting side effects of myelosuppression and peripheral neuropathy are well known. Paclitaxel has minimal penetration of the blood-brain barrier and central nervous system side effects are rare. However, transient encephalopathy following paclitaxel infusion has been described in adults but not in children. We present the case of a 14-year-old female with a recurrent suprasellar germinoma who developed an acute encephalopathy 4-6 hr following paclitaxel infusion.

Recurrent intracranial germinoma along the endoscopic ventriculostomy tract. Case report.

The authors report a case of a recurrent intracranial germinoma along the site of an endoscopic third ventriculostomy (ETV) after complete local tumor control using 3D conformal radiation therapy. A 13-year-old girl presented with sudden left upward gaze limitation for 4 days. A pineal region tumor and obstructive hydrocephalus were noted on magnetic resonance (MR) images. An ETV and tumor biopsy procedure were performed, which revealed the lesion to be a germinoma. The patient's visual symptoms and hydrocephalus disappeared postoperatively. Chemotherapy using cisplatin, etoposide, vincristine, and cyclophosphamide was initiated on postoperative Day 10. An MR image obtained 10 weeks after surgery and 2 weeks after chemotherapy revealed a significant (> 50%) reduction of the lesion. Radiation therapy was administered at 50.4 Gy to the target and 36 Gy to the periphery. Ten months after surgery, an MR image revealed further shrinkage of the tumor mass. One year after surgery, follow-up MR imaging demonstrated a small mass lesion at the entry site of the ETV, measuring 1.0 x 1.4 x 1.5 cm. An operation was performed to remove the small lesion, and pathological findings revealed it to be of the same histology as the primary tumor.