Hope Richard

Gliomatosis cerebri: Report of 3 cases

Gliomatosis cerebri is an uncommon glial neoplasm that is exceedingly rare in children and difficult to diagnose. The authors describe the presentation and diagnosis of GC in 3 children ages 12, 14, and 16 years. These children exhibited signs and symptoms of increased intracranial pressure as well as other vague or site specific neurological signs. Because clinical presentation, CSF analysis, and neuroimaging were nonspecific, a stereotactic biopsy to obtain tissue for pathological review was ultimately necessary to confirm the diagnosis. These pediatric cases underscore the limitations of relying solely on clinical presentation and neuroimaging and call to attention the essential role of neurosurgical intervention. The authors emphasize the need to maintain gliomatosis cerebri in the differential diagnosis of children presenting with diffuse neurological signs and MR imaging evidence of widespread, infiltrative lesions.

Pediatric Gliomatosis Cerebri Mimicking Acute Disseminated Encephalomyelitis

Gliomatosis cerebri (GC) is a diffuse infiltrating glial neoplasm of astrocytic origin. GC in children is rare and difficult to diagnose, often presenting with a variety of signs and symptoms that may mimic encephalitis. We discuss here the presentation and diagnosis of GC in 2 children who were initially suspected to have acute disseminating encephalomyelitis. In this report we underscore the limitations of relying on clinical presentation and neuroimaging as well as the essential role of pathologic evaluation for the diagnosis of GC in children.

An unusual case of schwannomatosis with bilateral maxillary sinus schwannomas and a novel SMARCB1 gene mutation.

Schwannomas are benign tumors that arise from Schwann cells in the peripheral nervous system. Patients with multiple schwannomas without signs and symptoms of neurofibromatosis Type 1 or 2 have the rare disease schwannomatosis. Tumors in these patients occur along peripheral nerves throughout the body. Mutations of the SMARCB1 gene have been described as one of the predisposing genetic factors in the development of this disease. This report describes a patient who was observed for 6 years after having undergone removal of 7 schwannomas, including bilateral maxillary sinus schwannomas, a tumor that has not been previously reported. Genetic analysis revealed a novel mutation of c.93G>A in exon 1 of the SMARCB1 gene.

Congenital Oligodendroglioma: Clinicopathologic and Molecular Assessment with Review of the Literature

Oligodendroglioma is an infiltrating glial neoplasm frequently seen in adults. Pediatric oligodendrogliomas are rare, with very few cases presenting in infancy and only rare congenital examples. In contrast to adult oligodendrogliomas, pediatric cases typically lack 1p/19q codeletion. Herein we report a case of WHO grade II oligodendroglioma diagnosed in a 7-month-old male infant. The patient initially presented at 3 months of age with symptoms suspicious for seizure. Initial workup including electroencephalography (EEG), electrocardiogram (EKG), and computed tomography (CT) of the head was negative. His symptoms persisted, and subsequent magnetic resonance imaging (MRI) performed at age of 7 months revealed a 2 cm contrast-enhancing left temporal lobe mass. The mass was excised and the microscopic appearance was that of a classic low grade oligodendroglioma composed of cells with uniformly round nuclei, perinuclear halos, delicate branching capillaries, and an absence of high grade features. Mutant specific (R132H) isocitrate dehydrogenase-1 (IDH1) immunohistochemistry was negative, and the tumor lacked detectable 1p or 19q deletions by fluorescent in situ hybridization (FISH). The onset of neurological symptoms in early infancy followed by the positive MRI findings suggests that this case represents a rare example of congenital oligodendroglioma.

Novel Role of the Nociceptin System as a Regulator of Glutamate Transporter Expression in Developing Astrocytes

Our previous results showed that oligodendrocyte development is regulated by both nociceptin and its G‐protein coupled receptor, the nociceptin/orphanin FQ receptor (NOR). The present in vitro and in vivo findings show that nociceptin plays a crucial conserved role regulating the levels of the glutamate/aspartate transporter GLAST/EAAT1 in both human and rodent brain astrocytes. This nociceptin‐mediated response takes place during a critical developmental window that coincides with the early stages of astrocyte maturation. GLAST/EAAT1 upregulation by nociceptin is mediated by NOR and the downstream participation of a complex signaling cascade that involves the interaction of several kinase systems, including PI‐3K/AKT, mTOR, and JAK. Because GLAST is the main glutamate transporter during brain maturation, these novel findings suggest that nociceptin plays a crucial role in regulating the function of early astrocytes and their capacity to support glutamate homeostasis in the developing brain.

Aberrant expression of TdT in seminomatous germ cell neoplasia

Dear Editor, We read with great interest the paper by Brobeil et al. [1] this month on the expression of terminal deoxynucleotidyl transferase (TdT) in seminoma. We would like to express our appreciation to the authors of this study for highlighting this potential diagnostic pitfall regarding the differential diagnosis with lymphoblastic lymphoma. We, too, have recent experience in this area, spurred by an index case of a germinoma arising in the mediastinum (a common site for precursor T lymphoblastic lymphoma) of a 23 year-old male (Fig. 1). TdT expression was diffuse, both at the primary site and at an osseous metastasis, which had caused diagnostic controversy prior to transfer of the patient to our institution and use of additional confirmatory germ cell markers. We would amplify and extend the Brobeil et al.’s findings by briefly describing our own findings with Baberrant^ TdT expression across seminoma, dysgerminoma, and extragonadal germinoma. To assess the prevalence of this pitfall in light of the aforementioned index case, we analyzed TdT expression in a tissue microarray (TMA, triplicate cores) constructed from routine archival paraffin-embedded tissues of 22 seminomas, 10 germinomas, and 3 dysgerminomas. Whole sections of three additional seminomas and one additional mediastinal germinoma were stained as well. The same TdT antibody clone (as used by Brobeil et al.), EP266 was used (predilute, 28 min, Ventana Benchmark XT autostainer, Optiview DAB IHC detection kit). Overall, 4 of the 25 seminomas (16%), 6 of the 12 extragonadal germinomas (50%), and 1 of the 3 dysgerminomas (33%) stained positively for TdT. Thus, our findings confirm the potential diagnostic pitfall of TdTexpression in seminoma, document this phenomenon in additional samples run in an independent CLIA-compliant clinical laboratory, and extend the pitfall to a number of extagonadal germinomatous tumors at additional sites where lymphoblastic lymphoma may be seen clinically. We note that Brobeil et al.’s report shows up to 100% positivity for TdT staining in the ten classic seminomas they studied with whole sections; this is certainly greater than the 16% of seminomas or even the 50% of extragonadal germinomas we observed. However, we have often seen patchy, geographically restricted TdT staining in whole sections of these tumors, which is likely undersampled by our mostly TMAbased analysis, and likely contributes to the lower proportion positive. Thus, in the end, while our TMA-based study might partly underestimate the true prevalence of positive TdT staining, we do not underestimate the importance of this newly recognized pitfall. Matthew George Gayhart, MD. Hope Richard, MD, PhD. Austin Blackburn Wiles, MD. Steven Christopher Smith, MD, PhD. * Steven Christopher Smith steven.c.smith@vcuhealth.org

Multiple extraspinal recurrences of ependymoma 13 years after spinal cordectomy: case report

Ependymomas of the spinal cord remain confined to the CNS and vary in presentation, depending on WHO grade. Higher-grade lesions usually cannot be surgically removed due to their infiltrative growth pattern. Spinal cordectomy has been proposed as a rescue treatment to improve survival in patients with high-grade as well as recurrent lesions. This report details an instructive and unique case of long-term follow-up of a patient who underwent cordectomy from T-4 through S-5 for what was initially diagnosed as a high-grade glial neoplasm of the spinal cord in 1993. The patient lived symptom free for 13 years after spinal cord resection and then presented with numerous bilateral extraspinal (intraabdominal and intrathoracic) tumors, which eventually led to her death 15 years after the cordectomy. In this case, spinal cordectomy was effective in preventing the ascending spread of the neoplasm, but ultimately not effective in preventing recurrence in the plicated distal dural sac.

Central Nervous System Tumors

A pragmatic approach to the molecular oncology of central nervous system tumors mandates a thorough but clinically relevant review of the molecular techniques utilized in most neuropathology practices for diagnosing intra-axial pediatric and adult tumors as well as extra-axial dural based lesions. In regards to the latter, techniques for both 1p/14q deletion and NGFI-A binding protein 2 (NAB2)-Signal transducer and activator of transcription 6 (STAT6) fusion status are detailed as useful clinical markers for meningiomas and hemangiopericytomas/solitary fibrous tumors, respectively. Due to the distinct molecular profiles of lesions found in different age groups, adult and pediatric central nervous system (CNS) tumors are discussed separately. The diagnostic, prognostic, and predictive values of molecular markers in adult gliomas are outlined, including MGMT (O6-methylguanine DNA methyltransferase), Isocitrate dehydrogenase 1/2 (IDH1/2), 1p19q, and epidermal growth factor receptor (EGFR). In addition to gliomas, molecular testing is also clinically useful in other pediatric neoplasms including medulloblastoma and atypical teratoid rhabdoid tumor (AT/RT). The techniques employed to evaluate the diverse molecular alterations found in CNS tumors include fluorescent in situ hybridization (FISH), direct sequencing, methylation specific PCR (MSP) and immunohistochemistry (IHC). This chapter is designed to provide a reference guide for the practicing pathologist and neuro-oncologist for common and relevant molecular alterations encountered in neoplasms of the CNS.

Headaches and hemiparesis in an immunocompetent inmate

© 2013 Japanese Society of Neuropathology. This is the peer reviewed version of the following article: Jelinek, A. G., Fuller, C., Baykal, A., Stogner-Underwood, K., Richard, H. and Arkun, K. (2014), Headaches and hemiparesis in an immunocompetent inmate. Neuropathology, 34: 314-317, which has been published in final form at doi: 10.1111/ neup.12084. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.