Faculty Bibliography

OBJECT: Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading. optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. METHODS: Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M and one with M3 stages). At surgery, 47% of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71%) had an isolated local relapse, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression-free survival (PFS) and overall survival rates were 50 +/- 10% and 64 +/- 9%, respectively. CONCLUSIONS: Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (< or = 1.5 cm2 compared with > 1.5 cm2, p < 0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy

OBJECTIVE: Tenascin-C (TN) is an extracellular matrix glycoprotein with a characteristic six-armed structure. The aim of this study was to determine whether the concentration of TN in the cyst fluid of brain tumors can be used as a marker for angiogenesis and glioma grade. METHODS: We investigated the expression of TN in the cyst wall and cyst fluid of human brain tumors by immunohistochemistry, immunoprecipitation, and immunoblotting. The tumors included 12 astrocytomas (5 glioblastoma multiforme tumors, 1 anaplastic astrocytoma, 1 low-grade astrocytoma, 4 juvenile pilocytic astrocytomas, and 1 mixed glioma), 2 dysembryoplastic neuroepithelial tumors, 3 craniopharyngiomas, 2 ependymomas, 2 metastatic carcinomas, 3 arachnoid cysts, 1 glial ependymal cyst, and 1 inflammatory cyst. RESULTS: We detected no expression of TN in the cyst fluids of the ependymomas, craniopharyngiomas, and nonpilocytic low-grade astrocytoma. By contrast, TN was detected in the cyst fluids of all the other tumors. Results of quantitative immunoblotting using a PhosphorImager unit (Molecular Dynamics, Sunnyvale, CA) revealed that, on average, a 5-fold higher signal was observed in the glioblastoma multiforme tumors as compared with the anaplastic astrocytoma, and a 10-fold higher signal as compared with the mixed glioma, juvenile pilocytic astrocytomas, and dysembryoplastic neuroepithelial tumors. Results of TN immunohistochemistry in the astrocytomas correlated with glioma grade, with stronger staining of the hyperplastic vessels and tumor cells being observed in higher grade gliomas. No TN immunoreactivity was detected in the walls of the ependymomas, arachnoid cysts, and glial ependymal cyst that lack hyperplastic vessels, and minimal TN immunoreactivity was observed in the perivascular gliotic rim of the craniopharyngiomas. No TN was detected in the cyst fluid of these cystic processes. CONCLUSION: The presence of TN in and around the hyperplastic vessels and tumor cells present in the cyst walls of astrocytomas and its deposition in the intratumoral cyst fluid in which angiogenic factors have been detected further suggests a role for TN as an angiogenic modulator. These preliminary results suggest that immunodetection of TN in the tumor cyst fluid may indicate tumor type and grade

Craniosynostosis is often associated with restrictive cranial vault deformities, diminished intracranial volume, and intracranial hypertension. Advances in imaging techniques have provided a method of intracranial volume analysis that has demonstrated a more complicated relationship between craniofacial abnormalities and elevated intracranial pressures. Studies have confirmed a decrease in intracranial volume in the presence of craniosynostosis, but this association is not found in every patient. We report an unusual case of elevated intracranial pressure in a patient with the clinical stigmata of Crouzon's syndrome but with patent cranial vault sutures

The etiology of craniosynostosis remains unknown. The beta group of transforming growth factors (TGF-beta) and insulin-like growth factors (IGF-I and IGF-II) are known to induce new bone formation and, when added exogenously, cause accelerated closure of calvarial defects. The possible roles of these bone growth factors in premature cranial suture fusion in humans have not been explored. We analyzed a total of 20 cranial suture biopsy samples (10 synostotic and 10 normal) from 10 infants with single-suture craniosynostosis undergoing cranial vault remodeling. Using isoform-specific antibodies for TGF-beta 1, -beta 2, and -beta 3 and IGF-I, we demonstrated immunoreactivity of these growth factors were present in human cranial sutures; the TGF-beta 2 isoform was the most intensely immunoreactive. Most importantly, the TGF-beta isoforms and IGF-I showed more intense immunoreactivity in the actively fusing craniosynostotic sutures compared with the control patent sutures. Specifically, the TGF-beta isoforms and IGF-I were intensely localized in the osteoblasts synthesizing new bone at the suture margin. It is noteworthy that although the patent sutures were less immunoreactive for TGF-beta isoforms than fused sutures, there was a distinct pattern of the TGF-beta 3 isoform that was immunolocalized to the margin of the normal patent sutures. This suggests a possible role for TGF-beta 3 in maintaining cranial suture patency. The increased immunoreactivity of both TGF-beta 2 and IGF-I in the actively fusing sutures compared with the patent control sutures indicates that these growth factors may play a role in the biology underlying premature suture closure. To our knowledge, this is the first study showing the presence of TGF-beta 1, -beta 2, and -beta 3 and IGF-I in prematurely fusing human cranial sutures. In the future, manipulating the local expression of these growth factors at the suture site may enable plastic surgeons to modulate premature suture fusion

OBJECTIVE:The optimal surgical management of arachnoid cysts remains controversial. The cerebellopontine angle (CPA) is a rare location for arachnoid cysts, and only 28 cases of arachnoid cysts occurring in the CPA have been reported in the literature. We discuss the diagnosis, radiographic imaging, and surgical management of CPA arachnoid cysts. METHODS:Five patients (three male and two female patients) with a mean age of 5.6 years have been operated on at our institution since 1980. Magnetic resonance imaging allows for the accurate diagnosis of these arachnoid cysts, which can present with only discrete symptoms, such as headache or ataxia. All five arachnoid cysts compressed the cerebellum or brain stem. One patient had associated hydrocephalus. Three patients presented with refractory headaches associated with nausea and vomiting. The remaining two patients presented with cerebellar signs. No patient had an initial cranial neuropathy. RESULTS:All patients underwent a retrosigmoid suboccipital craniotomy and microsurgical resection and fenestration of the cyst walls. One patient underwent two procedures. A cystoperitoneal shunt was inserted at the first operation. After the shunting procedure, the patient's condition deteriorated; however, after the microsurgical resection and fenestration, his symptoms improved. With a mean 5.2-year follow-up, there has been no evidence of clinical or radiographic recurrence. CONCLUSION/CONCLUSIONS:Although CPA arachnoid cysts represent a small number of total arachnoid cysts, the CPA is the second most common location for arachnoid cysts to occur. CPA cysts are congenital lesions found in children who present with subtle signs or symptoms. The definitive treatment for these arachnoid cysts is a retrosigmoid suboccipital craniotomy and microsurgical resection and fenestration of the cyst walls.

We present an unusual case of a craniopharyngioma with a visual field deficit related to optic tract compression by the anterior cerebral artery. The presentation and management of this case are described. Previous cases of visual field deficits associated with craniopharyngiomas are reviewed

Radical surgery is the most important treatment modality for ependymoma. The benefit of adjuvant radiotherapy and/or chemotherapy following a gross total resection of a low grade intracranial ependymoma is uncertain. Since 1990 we elected to defer adjuvant therapy in 7 pediatric patients with a median age of 7 years (range 3-16 years) who had a radical resection of an intracranial ependymoma and no evidence of central nervous system metastases. The primary tumor site was the cerebral hemisphere (6) and the cerebellum (1). A gross total resection was radiologically confirmed in 5 of the 7 patients. Two of the patients had a blood clot in the resection site on the postoperative magnetic resonance imaging scan. All patients are alive after a median follow-up of 44 months and the median progression-free survival is 38+ months. Five of the patients remain in continuous remission. The 2 patients with postoperative blood clots developed subclinical local recurrences, 10 and 11 months, respectively, after diagnosis. They remain in remission for 13+ and 27+ months after subsequent radical surgical procedures. Involved field radiotherapy was administered to 1 patient. After a limited period of follow-up, radical surgery alone appears to be sufficient for the majority of children with low grade ependymomas diagnosed at > 3 years of age when postoperative imaging confirms a gross total resection. This is more likely to occur in supratentorial ependymomas arising in older children