Brainstem Ganglioglioma Research Articles

Incidence and survival characteristics of pediatric ganglioglioma from 2004 to 2018, with focus on infratentorial sites.

Ganglioglioma (GG) is a slow-growing glioneuronal neoplasm, most frequently seen in the supratentorial location in older children and associated with epilepsy syndromes. GG is rare in the infratentorial location, hence we embarked upon analyzing the National Cancer Institute's (NCI) Survival, Epidemiology, and End Results (SEER) database to better evaluate GG outcomes by location in comparison to the broader pediatric low-grade glioma (pLGG) population. Pediatric patients diagnosed with GG and pLGG from 2004 to 2018 were included in the study. Their demographic, clinical, and survival characteristics were analyzed using SEER*Stat. This study describes the largest cohort of pediatric GG, including 852 cases from year 2004 to 2018, with focus on infratentorial sites. Patients with brainstem GG or those with subtotally resected disease were identified as having higher risk of death. Our analysis highlights brainstem GG as a high-risk, poor-prognostic subgroup and elaborates on the incidence and survival characteristic of this lesser-known subgroup.

LGG-36. Analysis of BRAF-related mutations in pediatric low-grade glioma

BACKGROUND: Most pediatric low-grade gliomas (pLGGs) are driven by a single genetic event resulting in up-regulation of the RAS/MAPK pathway. BRAF-related mutations are the most freauent molecular alteration in the pathway. To explore BRAF-related mutations in pediatric low-grade glioma is helpful for clinical practice. METHODS: In this study, patients with low-grade glioma aged ≤18 years in Guangdong Sanjiu Brain Hospital were enrolled. All patients accepted the tests of BRAF-related mutations with tumor tissue by next-generation sequencing (NGS). Results: A total of 26 patients diagnosed low-grade glioma and underwent NGS detection were included in this study. The male to female ratio was 6:7, and the median age was 9.5 years. 8 patients had tumors located in the cerebral hemisphere, 6 in the third or fourth ventricle, 5 in the cerebellum, 4 in the optic pathway, and 3 in the brain stem. A total of 14 patients took BRAF-related mutations, such as BRAF-KIAA1549 fusion, BRAF p.V600E mutation and other fusion. BRAF-KIAA1549 fusion was detected in 7 patients with pilocytic astrocytoma or pilomyxoid astrocytoma. BRAF p.V600E mutation was detected in 6 patients, two of whom were pleomorphic xanthoastrocytoma. A rare genetic fusion, BCAS1-BRAF fusion, was detected in 1 patient who had brain stem ganglioglioma. Among the 26 patients, 2 patients without BRAF-related mutations had typical multiple cafe-au-lait macules and were diagnosed as NF1-pLGG. These patients were treated with surgery, radiation, chemotherapy and targeted therapy. Only 2 patients received targeted therapy by Trametinib, Vimofinib and Everolimus after progression of the tumor. However, due to the severity of the disease, they eventually died. CONCLUSIONS: More than half of pLGG patients have BRAF-related mutations, which have the opportunity for targeted therapy. However, the optimal timing of targeted therapy still needs further exploration.

Microsurgical resection of brainstem cervicomedullary ganglioglioma: operative video and technique of creating a surgical pseudoplane for near-total resection.

Cervicomedullary gangliogliomas are rare low-grade neoplasms of the brainstem. They can be challenging lesions to resect due to the eloquent location in the brainstem. In some instances, the absence of a clear surgical plane between the tumor and normal neural tissue can prohibit a complete resection. Therefore, it is important to leave a thin rim of residual tumor at the tumor-brainstem interface in order to avoid irreversible neurological injury. In this operative video, the authors demonstrate the technique to develop a surgical pseudoplane using sharp microdissection for a cervicomedullary brainstem ganglioglioma without a clear interface between the tumor and normal neural tissue. This strategy allowed for radical near-total resection of the tumor, thereby maximizing the extent of removal while preserving neurological function. Postoperatively, the patient had normal neurological function and returned to work without any disability. In summary, due to the lack of a clear surgical dissection plane, a pseudoplane near the surgical interface can be performed using sharp dissection to facilitate radical near-total resection.The video can be found here: https://youtu.be/biD4G1Hh0yk.

BRAF V600E mutation is a significant prognosticator of the tumour regrowth rate in brainstem gangliogliomas

BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma’s clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma’s clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation. The volume of tumours was calculated accurately by using 3D Slicer software. The clinical data of these patients were retrospectively analysed. In tumours with BRAF V600E mutations, the tumour regrowth rate was significantly faster than that of the wild type group (p=0.001). Moreover, the BRAF V600E mutant group had shorter progression-free survival (PFS) compared with wild type (p=0.012). On multivariate analysis, no factor was found to be an independent prognostic factor; however, tumours with faster regrowth rates had a strong trend towards an increased risk for shorter PFS (HR=1.027, p=0.056). No statistical analysis could be performed to evaluate factors affecting overall survival (OS). These data suggest that BRAF V600E can predict the regrowth rate of brainstem gangliogliomas after microsurgery, and a BRAF V600E-targeted therapeutic may be a promising early intervention measure for patients who harbour BRAF V600E mutation after microsurgery.

Clinical features and microsurgical treatment of brainstem gangliogliomas

Objective To analyze the clinical and imaging features, microsurgical strategy and prognosis of brainstem gangliogliomas. Methods We retrospectively analyzed a cohort of 25 brainstem gangliogliomas treated at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from May 2008 to September 2015. The clinical manifestation, imaging features, microsurgical methods and prognosis were reviewed. Results The median age of 25 patients was 22 (range: 5-45) years, median history was 12 (range: 1-384) months and the preoperative Karnofsky Performace Status (KPS) scores ranged from 20 to 100. On the enhanced sagittal MRI, 17 (68%) tumors were characterized by a unique patchy appearance. On the enhanced axial MRI, 11 tumors (44%) demonstrated acrescent sign. Among all patients, total resection was achieved in 7 cases, near total resection in 5 cases, subtotal resection in 8 cases, partial resection in 4 cases and biopsy in 1 case. No operative death occurred. The follow-up time ranged from 3 to 97 months, with an average follow-up of (50.5 ± 27.7) months. There were 3 cases developing severe postoperative complications and 3 death cases observed during the follow-up. The median PFS of non-infiltrating group (53.0 months) was longer than that of infiltrating group (21.5 months) (P<0.05). Tumor recurrence occurred in 8 cases in a short period of time postoperatively but did not present with symptom aggravation. Conclusions Most brainstem gangliogliomas seem to have some unique MRI characteristics. Microsurgical resection might be preferred. Tumors located outside the brainstem could be fully removed, while those infiltrating the brainstem should not be resected with risks. Postoperative short-term tumor recurrence without clinical symptom deterioration could be closely monitored. Key words: Brain stem neoplasm; Ganglioglioma; Signs and symptoms; Microsurgery; Prognosis

A Phase II Study of Antineoplastons A10 and AS2-1 in Children with Brain Tumors. Final Report (Protocol BT-10)

Despite dramatic progress over the last 50 years in the treatment of many childhood cancers, primary brain tumors remain the leading cause of death in pediatric oncology. This phase II study evaluated the efficacy and safety of Antineoplastons A10 and AS2-1 given in combination (ANP). Thirty-four patients, with a median age of 10.4 years, were enrolled in the study. Thirty-two patients (94.1%), were Caucasians while 21 (61.8%) were female and 13 were male (38.2%). Twenty-four patients (70.6%) suffered from a brainstem glioma (BSG) or high-grade tumor. Ten patients (29.4%) suffered from a low-grade tumor. A distinct sub-group of three patients with low grade tumors had a ganglioglioma (GG). Eighty-two percent of patients had failed standard treatment. Daily ANP was administered by IV infusion, every four hours, until an objective response (OR) was documented, and then for an additional eight months. The median doses of A10 and AS2-1 were 11.64 g/kg/d and 0.45 g/kg/d, respectively. A complete response (CR) was documented in two patients (5.9%), a partial response (PR) in four patients (11.8%), and stable disease (SD) in six patients (17.6%). Objective responses were observed in diffuse intrinsic pontine glioma (DIPG), thalamic pilocytic astrocytoma with brainstem involvement, ganglioglioma and pilocytic astrocytoma. Six-month progression-free survival (PFS) was 35.3%. Overall survival (OS) at two and five years was 37.6% and 34.5%, respectively. Two patients experienced grade 4 hypernatremia while three experienced grade 3 hypokalemia. In this group of patients, ANP showed good efficacy and an acceptable toxicity profile.

LG-44OCCURRENCE OF BRAF V600E MUTATION IN A PEDIATRIC BRAINSTEM GANGLIOGLIOMA WITH NEAR EXCLUSIVE GLIAL COMPONENT IN THE ORIGINAL BIOPSY

LG-44. OCCURRENCE OF BRAF V600E MUTATION IN A PEDIATRIC BRAINSTEM GANGLIOGLIOMA WITH NEAR EXCLUSIVE GLIAL COMPONENT IN THE ORIGINAL BIOPSY Alex Feldman, David Kelly, Alyssa Reddy, Jeffrey Blount, and Rong Li; University of Alabama at Birmingham, Birmingham, AL, USA A five-year-old male who initially presented with apneic episodes and morbid obesity underwent imaging studies, which revealed a dorsally exophytic medullary tumor in 2014. A biopsy showed a classic pilocytic astrocytoma (PA) with no apparent neoplastic neuronal component. Following completion of chemotherapy, the patient presented again in January of 2016 with worsening symptoms; the tumor was found to have grown in size with brainstem compression. Debulking was performed. Unexpectedly, the histology of this tumor showed a ganglioglioma (GG) with many clusters of enlarged, misshapen, dysmorphic-appearing and occasionally binucleated neurons. Furthermore, BRAF V600E mutations were identified in both prior and recurrent tumors. Recent publications have found that the BRAF V600E mutation is seen in 20-58% of all GGs. In particular, pediatric brainstem GGs appear to harbor this mutation at a rate greater than 50%. Few studies have investigated the distribution of BRAF aberrations among neuronal and glial components in GGs. Pilocytic astrocytomas often possess BRAF abnormalities, though fusion genes (i.e BRAF-KIAA1549) are considerably more common (60-80%) than the BRAF V600E missense mutations (only seen in 10-12% of pediatric brainstem PAs). This case highlights the presence of the BRAF point mutation in both glial and neuronal component of a pediatric brainstem GG, supporting the hypothesis that a glioneuronal lineage precursor is initially affected by the mutation. Additionally, the presence of the BRAF point mutation in a brainstem pilocytic astrocytoma should raise the possibility of a GG in which sampling artifact highlights a near exclusive glial component. Neuro-Oncology 18:iii78–iii96, 2016. doi:10.1093/neuonc/now075.44 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brainstem gangliogliomas: prognostic factors, surgical indications and functional outcomes.

To explore the prognostic factors and discuss the surgical indications of brainstem gangliogliomas. Twenty-one patients with brainstem ganglioglioma were surgically treated at our hospital between 2006 and 2014. The clinical, radiological, operative, and pathological findings of these patients were retrospectively reviewed. The 3-years overall survival and event-free survival (EFS) rates were 90.5% and 68.4%, respectively. Four patients (4/18, 22%) experienced a recurrence with a mean recurrence-free survival of 5.5months and a mean follow-up of 37months. Three patients died of surgery-related complications. Three growth patterns were identified: exophytic (6/21), intrinsic (2/21), and endo-exophytic (13/21). Eight patients (8/15, 53%) harbored a BRAF V600E mutation. All recurrent tumors were endo-exophytic, and except the one without molecular information, were BRAF V600E mutants. A Cox hazard proportion ratio model was used to identify factors influencing EFS, including sex, age, location, growth patterns, extent of resection (EOR), and BRAF V600E mutation status. On univariate analysis, none of these factors reached statistical significance. Among them, EOR and growth patterns were strongly associated with each other (Fisher's exact test, P<0.01). A multivariate analysis demonstrated that growth patterns were the only factor associated with EFS (P=0.02; HR 49.05; 95% CI 1.76-1365.13). Growth patterns may be useful to select surgery candidates and predict prognosis for patients with brainstem gangliogliomas. BRAF V600E was frequently present and appeared to be associated with shorter recurrence-free survival. Studies on BRAF V600E-targeted therapy for patients with high surgical risks are needed.

Radiological Evaluation of Infratentorial Gangliogliomas in Various Anatomic Locations of the Cerebellum and Brainstem.

To review the imaging features of infratentorial gangliogliomas (GGs) and compare between Infratentorial GGs located within the cerebellum and brainstem. The cases of 24 patients with histologically-confirmed infratentorial GGs were reviewed retrospectively. These subjects' cases were divided into a cerebellar group (n = 8) and a brainstem group (n = 16) based upon the anatomic location of the tumor. Imaging features (including tumor volume, margins, cystic/solid ratio, enhancement, peritumoral edema, and ipsilateral cerebellar atrophy) were compared between these two groups. On magnetic resonance imaging, infratentorial GGs showed isointensity or hypointensity on T1WI and heterogeneous hyperintensity on T2WI, with ipsilateral cerebellar atrophy observed in seven cases. Computed tomography images available in the cerebellar group showed heterogeneous isodensity with calcifications. Cerebellar GGs (median = 67.25cm3, inter-quartile range = 27.78-83.27cm3) were larger in volume than brainstem GGs (median = 16.89cm3, interquartile range = 6.08-27.26cm3) (p = 0.002). Cystic-solid mass (5 of 8) and solid mass (11 of 16) were more commonly represented in the cerebellar and brainstem group, respectively (p = 0.033). Cerebellar GGs showed varying degrees of enhancement, while most of brainstem GGs showed moderate-to-marked enhancement (p = 0.012). Dorsal-predominant enhancement (n = 3) and posterior-marginal enhancement (n = 5) were observed in the brainstem group. The degrees of peritumoral edema and rate of ipsilateral cerebellar atrophy were not significantly different between the two study groups. Ipsilateral cerebellar atrophy can be found in infratentorial GGs involving the middle and inferior cerebellar peduncles. GGs should therefore be considered in the differential diagnoses when a solid-cystic mass with calcification is encountered in the cerebellum. Brainstem GGs tend to be smaller, solid masses with moderate-to-marked enhancement. Dorsal-predominant and posterior-marginal enhancement may be the specific imaging findings for brainstem GGs.

Intramedullary gangliogliomas: histopathologic and molecular features of 25 cases

Gangliogliomas are uncommon glioneuronal tumors, which usually arise in the cerebral hemispheres and occasionally in the brain stem. Gangliogliomas occurring in the spinal cord are extremely rare. In this study, we analyzed the clinical, histopathologic, and molecular features of 25 spinal gangliogliomas. The cases included in our series affected mostly children and young adults (15 males and 10 females; mean age, 20 years; median age, 14 years; age range, 1-72 years) and were predominantly localized in the cervical and thoracic spine. From the clinical point of view (detailed follow-up available for 9 pediatric cases; mean follow-up: 2 years 10 months; range, 3 months to 5 years 10 months), most patients showed stable disease after subtotal resection. Radiotherapy was rarely used as adjuvant treatment. Histologically, gangliogliomas (WHO grade I) (21 cases) showed features largely similar to their supratentorial counterparts. Anaplastic gangliogliomas (World Health Organization grade III) (4 cases) showed features of anaplasia (including high cellularity and increased mitotic and proliferation activity). From a molecular point of view, only 2 tumors (2/19, 11%) harbored a BRAF(V600E) mutation. In conclusion, although spinal gangliogliomas display histologic and clinical features similar to their supratentorial counterparts, they show a relatively low frequency of BRAF(V600E) mutations, alteration otherwise common in hemispheric and brain stem gangliogliomas.

Suggestive value of predilection site and imaging features of pediatric brainstem ganglioglioma including a case report

Brainstem ganglioglioma is rarely reported. Due to its low incidence and atypical site, a brainstem ganglioglioma could easily be misdiagnosed as occurs with other pathological neoplasms radiologically. Here, we report an 8-year-old girl with a brainstem tumor confirmed as a ganglioglioma based on postoperative pathology results. We suggest that when a tumor located in the lower brainstem with benign radiological characteristics occurs in a child with a long-term history, the possibility of brainstem ganglioglioma should be considered in the preoperative diagnosis in addition to other low-grade neoplasms. Early stage diagnosis of brainstem ganglioglioma based on the clinical and imaging features is valuable for clinicians in order to perform effective treatment and achieve a good prognosis.

An enigmatic brainstem posterior fossa ganglioglioma in an adult

Ganglioglioma is a rare central nervous system neoplasm representing 0.4% to 1.7% of all brain tumors and most frequently occurs in the pediatric population with an incidence of 7.6%. These tumors are usually slow-growing and well-circumscribed solid or cystic lesions. Gangliogliomatosis infrequently occurs in the frontal lobe, pineal gland, basal ganglia, hypothalamus, and optic chiasm, with very few reports of brainstem ganglioglioma. We report a case of a 35-year-old female who initially presented with headache, vertigo, ataxia, saccadic dysfunction, dysarthria, and dysmetria for several years due to an unknown etiology. Her brain imaging showed multiple lesions in the pons and the cerebellum with cystic changes and size reduction and enlargement over the next few years while her neurological symptoms continued to worsen. The patient received courses of steroid treatment that improved her neurological symptoms, suggesting an inflammatory component of her disease. Extensive workup for an inflammatory or infectious etiology was unfruitful and two brain biopsies were inconclusive. A third biopsy showed atypical glial nuclei, binucleated cells, and Rosenthal fibers and the presence of BRAF V600E mutation was detected. The diagnosis of gangliogliomatosis was consequently established. This case illustrates that gangliogliomatosis may present with the waxing-and-waning neurological signs and symptoms. It can masquerade inflammatory processes in the central nervous system on brain imaging and deserves careful consideration in the diagnosis of patients with an indolent course of neurological deterioration.

Pediatric Brainstem Gangliogliomas Show BRAFV600E Mutation in a High Percentage of Cases

Brainstem gangliogliomas (GGs), often cannot be resected, have a much poorer prognosis than those located in more common supratentorial sites and may benefit from novel therapeutic approaches. Therapeutically targetable BRAF c.1799T>A (p.V600E) (BRAF(V600E) ) mutations are harbored in roughly 50% of collective GGs taken from all anatomical sites. Large numbers of pediatric brainstem GGs, however, have not been specifically assessed and anatomic-and age-restricted assessment of genetic and biological factors are becoming increasingly important. Pediatric brainstem GGs (n = 13), non-brainstem GGs (n = 11) and brainstem pilocytic astrocytomas (PAs) (n = 8) were screened by standard Sanger DNA sequencing of BRAF exon 15. Five of 13 (38%) pediatric GG harbored a definitive BRAF(V600E) mutation, with two others exhibiting an equivocal result by this method. BRAF(V600E) was also seen in five of 11 (45%) non-brainstem GGs and one of eight (13%) brainstem PAs. VE1 immunostaining for BRAF(V600E) showed concordance with sequencing in nine of nine brainstem GGs including the two cases equivocal by Sanger. The equivocal brainstem GGs were subsequently shown to harbor BRAF(V600E) using a novel, more sensitive, RNA-sequencing approach, yielding a final BRAF(V600E) mutation frequency of 54% (seven of 13) in brainstem GGs. BRAF(V600E) -targeted therapeutics should be a consideration for the high percentage of pediatric brainstem GGs refractory to conventional therapies.

Brainstem gangliogliomas: a retrospective series

The authors retrospectively analyzed data on brainstem gangliogliomas treated in their department and reviewed the pertinent literature to foster understanding of the preoperative characteristics, management, and clinical outcomes of this disease. In 2006, the authors established a database of treated lesions of the posterior fossa. The epidemiology findings, clinical presentations, radiological investigations, pathological diagnoses, management, and prognosis for brainstem gangliogliomas were retrospectively analyzed. Between 2006 and 2012, 7 patients suffering from brainstem ganglioglioma were treated at the West China Hospital of Sichuan University. The mean age of the patients, mean duration of symptoms prior to diagnosis, and mean duration of follow-up were 28.6 years, 19.4 months, and 38.1 months, respectively. The main presentations were progressive cranial nerve deficits and cerebellar signs. Subtotal resection was achieved in 2 patients, and partial resection in 5. All tumors were pathologically diagnosed as WHO Grade I or II ganglioglioma. Radiotherapy and adjuvant chemotherapy were not administered. After 21-69 months of follow-up, patient symptoms were resolved or stable without aggravation, and MRI showed that the size of residual lesions was unchanged without progression or recurrence. The diagnosis of brainstem ganglioglioma is of great importance given its favorable prognosis. The authors recommend the maximal safe resection followed by close observation without adjuvant therapy as the optimal treatment for this disease.

Brainstem ganglioglioma in an infant: Case report and review of literature

Gangliogliomas are well differentiated, usually low grade, neuroepithelial tumors that comprise of neoplastic ganglion cells in combination with neoplastic glial cells. Occasionally, glial cells may show anaplastic features and are then labeled as anaplastic gangliogliomas. Most of the reported gangliogliomas are supratentorial tumors, predominantly in the temporal lobe. Brainstem location has been reported infrequently. As with cortically based gangliogliomas, though the primary treatment is resection, this is often not possible due to the eloquence of surrounding involved parenchyma. Here, we report a case of brainstem tumor in an 8-month-old child that was substantially resected and was histopathologically Grade 1 ganglioglioma. As per review of English literature, there has been no case of brainstem ganglioglioma reported in an infant (less than 1 year age). We discuss the surgical difficulties in the radical excision of such benign tumors and review literature on pediatric brainstem gangliogliomas.

Location, location, location—gene expression studies of brainstem ganglioglioma: A rare tumor in a very rare location

Location, location, location—gene expression studies of brainstem ganglioglioma: A rare tumor in a very rare location

Pediatric brainstem gangliogliomas show overexpression of neuropeptide prepronociceptin (PNOC) by microarray and immunohistochemistry

Gangliogliomas (GGs) primary to brainstem are rare, with the overwhelming majority of GGs occurring in supratentorial, especially temporal lobe, locations. A less favorable prognosis exists for brainstem GGs, despite their usually identical WHO grade I status. Few large clinical series, and limited biological information, exists on these tumors, especially gene expression. Seven pediatric brainstem GGs, all with classic histological features, seen at our institution since 2000 were identified. Frozen section material was available for gene expression microarray profiling from five of seven brainstem GGs and compared with that from three non-brainstem pediatric GGs. Significant upregulation of a number of genes was identified, most of which were involved in pathways of neural signaling, embryonic development, and pattern specification in pediatric brainstem GGs compared to non-brainstem. The single largest upregulated gene was a 256-fold increase in the expression of the neuropeptide prepronociceptin (PNOC); the protein product of this gene has been implicated in neuronal growth. Overexpression was validated by Western blot and by immunohistochemistry (IHC). Strong IHC expression of PNOC was seen in neoplastic neurons of 7/7 brainstem GGs, but was significantly weaker in non-brainstem GGs, and completely negative in normal pediatric autopsy brainstem controls. PNOC IHC was often superior to IHC for NeuN, synaptophysin, or neurofilament for highlighting neoplastic neurons.

Brainstem Ganglioglioma

Gangliogliomas are usually benign slow-growing neoplasms, seen mainly in the first 3 decades of life and are prevalently located supratentorial, mostly in the temporal and frontal lobe. The authors present a rare case of a brainstem ganglioglioma in an 11-year-old boy who was referred to their hospital complaining of episodes of blurry vision, loss of memory, gait disturbances, and morning headache with vomiting, lasting for over a month. Computed tomography and magnetic resonance imaging scans revealed a mass on the dorsal surface of the brainstem, compressing the brainstem and producing secondary obstructive hydrocephalus. The patient was operated upon, and the histopathology revealed the presence of a ganglioglioma grade II (World Health Organization classification). On follow-up examination after 1 year, a minor gait imbalance was the only finding. A total resection should be always attempted, where possible in brainstem gangliogliomas. Close follow-up is mandatory, and re-resection or radiotherapy should be considered in case of tumor recurrence.

Ganglioglioma of the brainstem: Report of three cases and review of the literature

BACKGROUND Brainstem gangliogliomas are rare low-grade tumors that usually have a long clinical history. However, they may cause sudden death. There are only 31 cases of brainstem ganglioglioma reported in the literature, and only one has been studied with magnetic resonance (MR). We present three new cases of brainstem ganglion cell tumor studied with computed tomography (CT) (3 cases) and MR (2 cases) and discuss the clinical presentation, diagnostic imaging and treatment of these tumors. CASE DESCRIPTION Age at presentation ranged from 19 to 59 years old. Two patients were female and 1 male. Duration of symptoms before diagnosis ranged from 1 year to nearly 14 years. Presenting complaints included syncope spells, cranial nerve deficits, headache, and gait instability. Imaging studies revealed well-circumscribed lesions involving the brainstem; the lesion was cystic in one case and calcified in one. They were iso- or hyperdense on CT scan, isodense on T1-weighted and hyperdense on T2-weighted MRI and frequently showed contrast enhancement. All tumors were operated through a posterior fossa craniectomy. Using microsurgical techniques only partial resection could be achieved, as there was no sharp delineation from the surrounding tissue in any case. Two of our patients had increased neurological deficits after surgery. Radiotherapy was not given. Follow-up of tumoral remnants has not shown clear tumor growth after 1, 3.5, and 10 years. CONCLUSIONS Imaging characteristics of brainstem gangliogliomas do not seem to differ from those in other locations and are not specific. Radical surgery is rarely if ever possible, nor is it advisable because of the risk of functional deterioration. However, because of their benign histology, partial resection seems to carry a similar prognosis as tumors in other locations that are amenable to complete resection.

SYNAPTOPHYSIN STAINING IN NORMAL BRAIN

Neuronal and mixed glioneuronal tumors traditionally have comprised a very small percentage of intrinsic central nervous system neoplasms, although they are somewhat more common among juvenile brain tumors and in the temporal lobe. Neuronal differentiation increasingly is recognized in pleomorphic xanthoastrocytoma, intraventricular neurocytoma, and subependymal giant cell astrocytoma. However, the diagnostic distinctions between subtle ganglioglioma (with rare neurons) and infiltrating glioma with entrapped neurons and between infiltrating oligodendroglioma and parenchymal neurocytoma are problematic but may be clinically important. Recently, it was proposed that perisomatic synaptophysin immunostaining in the human central nervous system reliably and selectively discriminates neoplastic from nonneoplastic neurons. Using this criterion, the number of brain stem and spinal cord gangliogliomas could be increased substantially. We canvassed synaptophysin immunostaining patterns in the normal brain stem, cerebellum, and forebrain, and found that synaptophysin-positive neurons are distributed broadly in the normal human brain. In disturbed neocortical tissue, such as near vascular malformations, synaptophysin-positive neurons and irregular white-matter synaptophysin immunostaining are visualized. Although synaptophysin-positive neurons are found in gangliogliomas and archipelagos of synaptophysin reactivity are found in neurocytomas, these patterns clearly are not pathognomonic for glioneuronal tumors and must be interpreted with caution whenever other histologic or ultrastructural evidence of neuronal differentiation is lacking.