David C.Y. Low

Characterization of anaplastic lymphoma kinase-positive medulloblastomas

Medulloblastomas are the most common pediatric malignant primary brain tumor. To our knowledge, there are no known critical and druggable tyrosine kinases in medulloblastomas, precluding the use of established tyrosine kinase inhibitors that have shown efficacy in other tumor types. We studied the expression of anaplastic lymphoma kinase (ALK), a well-characterized tyrosine kinase and drug target, in a cohort of medulloblastomas by immunohistochemistry, and identified three ALK-positive cases. Mutational analyses did not reveal a definite underlying genetic mechanism for the ALK expression, although one of the cases showed increased ALK copy number. Our findings have clinical implications and warrant further pharmacological and functional studies, as well as evaluation in larger patient cohorts, to fully characterize the value of ALK as a prognostic and predictive therapeutic marker in medulloblastomas.

Synchronous Chiari III Malformation and Polydactyly

BACKGROUND Chiari III malformation is an extremely rare congenital anomaly. At present, its primary and associated pathognomonic factors remain poorly understood. The authors report a case of a male neonate born with an occipital encephalocoele with herniation of posterior fossa contents associated with bilateral postaxial polydactyly. CASE DESCRIPTION The patient is a dichorionic, diamniotic twin conceived via assisted reproductive methods; his twin sister has no congenital anomaly. Neurosurgical management included successful repair of the encephalocoele and subsequent cerebrospinal fluid diversion via a ventriculoperitoneal shunt. CONCLUSIONS Owing to the uniqueness of this patients presentation, the concurrent diagnoses of Chiari III malformation and polydactyly are discussed in concordance with updated literature.

Intra-operative cerebrospinal fluid sampling versus post-operative lumbar puncture for detection of leptomeningeal disease in malignant paediatric brain tumours

Introduction Leptomeningeal disease is a feared sequelae of malignant paediatric brain tumours. Current methods for its detection is the combined use of cranio-spinal MRI, and CSF cytology from a post-operative lumbar puncture. In this study, the authors hypothesize that CSF taken at the start of surgery, either from an external ventricular drain or neuroendoscope will have equal sensitivity for positive tumour cells, in comparison to lumbar puncture. Secondary hypotheses include positive correlation between CSF cytology and MRI findings of LMD. From a clinical perspective, the key aim of the study was for affected paediatric patients to avoid an additional procedure of a lumbar puncture, often performed under anaesthesia after neurosurgical intervention. Methods This is single-institution, retrospective study of paediatric patients diagnosed with malignant brain tumours. Its main aim was to compare cytological data from CSF collected at the time of surgery versus data from an interval lumbar puncture. In addition, MRI imaging of the same cohort of patients was examined for leptomeningeal disease and corroborated against CSF tumour cytology findings. Results Thirty patients are recruited for this study. Data analysis demonstrates a statistically significant association between our intra-operative CSF and LP sampling. Furthermore, our results also show for significant correlation between evidence of leptomeningeal disease on MRI findings versus intra-operative CSF positivity for tumour cells. Conclusion Although this is a retrospective study with a limited population, our data concurs with potential to avoid an additional procedure for the paediatric patient diagnosed with a malignant brain tumour.

Cystic Cavernoma of Fourth Ventricle in Pediatric Patient

BACKGROUND Cystic cerebral cavernomas belong to a rare subset of cavernous malformations in the brain. At present, there is limited information with regard to the demographics and etiology of this condition. CASE DESCRIPTION The authors present a case of a previously well 13-year-old male who presented with symptoms secondary to a cystic lesion of the fourth ventricle compressing on his brainstem. He underwent stereotactic aspiration of the cystic lesion and insertion of an Ommaya reservoir in the same setting. Postoperatively, his symptoms improved. The cyst fluid did not yield any positive cytology or culture results. A repeat MRI brain did not demonstrate evidence of any underlying lesion. However, the patient was readmitted for hemorrhage into the region of his previous fourth ventricular lesion. Surgical evacuation of the haematoma was performed and intraoperative tissue was sent for pathological interrogation. The final histology reported a cavernoma. CONCLUSIONS This is an unusual presentation of an intracranial vascular anomaly in a pediatric patient. Key features of the case include the diagnostic dilemma and management challenges faced from a neurosurgical perspective.

Medulloblastoma with tri-vergent melanocytic, myogenic and cartiligious elements

Neurosurgical Service, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore Department of Neurosurgery, National Neuroscience Institute, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore Dept of Pathology & Laboratory Medicine, KK Women’s and Children’s Hospital, 100 Bukit Timah Road, Singapore 229899, Singapore d SingHealth Duke-NUS Neuroscience Academic Clinical Program, Singapore

Concurrent paediatric medulloblastoma and Chiari I malformation with syringomyelia

Dear Editor: The concurrence of posterior fossa medulloblastoma and Chiari 1 malformation with syringomyelia in a paediatric patient is extremely rare. At present, the existence of a pathophysiological relationship between these two conditions remains unknown. We report a case of a previously well 9-year-old male who was admitted for progressive symptoms of headache, nausea and vomiting. There was no history of neck pain or dissociated sensory loss. A magnetic resonance imaging (MRI) scan of the brain and spine reported a 4.0 × 4.2 × 5.1 cm intraventricular midline posterior fossa mass associated with obstructive hydrocephalus. Simultaneously, cerebellar tonsillar herniation resulting in crowding of the foramen magnum was observed. There was also a long segment central cord syrinx extending from the level of C2 to T6 vertebral level causing cord expansion (Fig. 1a–c). The patient underwent a posterior fossa decompression, partial removal of C1 arch and removal of the tumour. A thickened, fibrous epidural band was found at the craniocervical junction after paraspinal muscle dissection. This structure was released prior to dura opening. Intradurally, there was congestion of bilateral cerebellar tonsils and caudal herniation via the foramen magnum. The tonsils were surgically shrunk to treat the herniation, allowing adequate space within the foramen magnum. Next, the intra-axial lesion underwent resection. Final histological diagnosis confirmed the lesion to be a medulloblastoma (classic type). Molecular interrogation using NanoString nCounter assay demonstrated the tumour to be a group 4 subtype. (Fig. 2a–c). Post-operatively, the patient was commenced on adjuvant chemo-radiation treatment as per institutional protocol. Medulloblastoma is the most common paediatric brain tumour. Most commonly arising in the posterior fossa, it causes symptoms of raised intracranial pressure and, or cerebellar dysfunction. Conversely, Chiari malformations encompass a broad spectrum of neurodevelopmental disorders, some of which are unlikely to share a common pathophysiology [1]. It is characterized by caudal herniation of the cerebellar tonsils exceeding 5 mm below the foramen magnum. Up to 70% of affected patients have concurrent syringomyelia—cystic cavitation of the spinal cord [2]. There is no universally accepted theory explaining Chiari 1 malformation and its associated anomalies [2]. At present, there are only a small number of reported cases of Chiari 1 malformation with syringomyelia associated with posterior fossa medulloblastoma, as previously summarized by Qi et al. [3]. * Sharon Y. Y. Low sharon.low.y.y@singhealth.com.sg

Anomalous intracranial germinoma with unilateral cerebral peduncle swelling

Dear Editor: Intracranial germinoma (IG) constitutes 0.5–2.0% of all primary brain tumours. It is usually found in the paediatric to young adult population. Up to 90% of germinomas develop in the midline, mainly in the pineal and suprasellar regions, but occasional occurrences in the basal ganglia, thalamus and midbrain have been reported [1, 2]. In most cases, the diagnosis of IG is based on a straightforward constellation of age, ethnicity, midline location of tumour with imaging-specific characteristics, neurological signs and/or endocrine dysfunction. The authors describe a case of IG who presented with unusual imaging features that resulted in a diagnostic challenge, and discuss the findings in corroboration with current literature. A previously well 12-year-old male presented with right-sided weakness over a month. There was no associated trauma or constitutional symptoms. A magnetic resonance imaging (MRI) of his brain showed a 1.5 × 1.3 cm region of mildly increased T1 and T2 hyperintensity involving a swollen left cerebral peduncle, posterior limb of the left internal capsule and left thalamus. The same area demonstrated mild post-contrast enhancement (Fig. 1). The provisional diagnosis of subacute infarct versus demyelinating disease was considered. An additional consideration was t h a t o f a neop l a sm a f f e c t i ng t h e r e l a t ed intraparenchymal structures. A follow-up magnetic imaging spectroscopy (MRS) revealed elevated choline and NAA (Cho/NAA) levels, compared to the spectrum obtained from the contralateral cerebral peduncle. There were no significantly elevated lipid levels. Diffusion tensor imaging (DTI) showed that the lesion was lateral to the left corticospinal tract, with minimum attenuation of the left corticospinal tract. Further investigations, including alpha-fetoprotein (αFP) and beta-human chorionic gonadotropin (βHCG) in the serum and cerebrospinal fluid (CSF), were unremarkable. Furthermore, CSF cytology did not show evidence of malignant cells. Biopsy of the left cerebral peduncle lesion, in corroboration with the DTI results , was performed. Final histology reported germinoma (Fig. 2). Subsequently, the patient was referred to medical oncology for adjuvant treatment. Intracranial germinomas have been reported to demonstrate specific types of MRI enhancement [1], which are observed in computed tomography (CT) and MRI scans in up to 33% of cases. They usually appear as isoand hyperdense solid masses relative to the grey matter and enhanced by contrast. At times, heterogeneity on T1and T2-weighted MRI images is seen in atypical germinomas, reflecting concomitant solid and cystic portions of the tumour. In recent years, MRS has gained prominence in the evaluation of intracranial lesions. Increased Cho/NAA levels, in tandem with large lipid peaks (Lip/Cr ratio), have been shown in IGs originating in the pineal region [3]. Although MRS was utilised for our patient, there were no outstanding lipid peaks observed. More significantly, there is a known association between ipsilateral cerebral atrophy and basal ganglia IG [2, * Sharon Y. Y. Low sharon.low.y.y@singhealth.com.sg