Mixed glioneuronal tumors of the spinal cord in two children

Abstract

Advances in immunohistochemistry have helped to improve classification schemes for central nervous system tumors. Particularly striking has been the recent attention on a growing list of neoplasms with mixed glial and neuronal elements [2]. These include well-defined examples like gangliogliomas and rosetted glioneuronal tumors, as well as newer entities that are currently difficult to classify, often designated simply as mixed glioneuronal tumors (GNT) [1, 5]. At least 43 cases of low grade GNTs have been reported, to which over 40 malignant forms have been recently added [8, 9]. It is unclear whether these glioneuronal tumors belong to a single category or represent multiple diagnostic entities. At least 11 of the documented low-grade tumors have been of the ‘rosetted’ variant, of which only 1 was located in the spinal cord [3]. We present 2 additional cases of mixed GNTs located in the thoracic spinal cord, 1 of which had clear areas of neurocytoma-like ‘rosetting’. Both were seen in children, had associated syringomyelia, and displayed overlapping histological features reminiscent of pilocytic astrocytomas. The first case is a 2-year-old boy, who presented with a 2-week history of weakness and ataxia, with magnetic resonance imaging (MRI) evidence of an intramedullary fluid-filled syrinx spanning the entire length of the spinal cord from C2 down to the conus (Fig. 1a). Also present in the thoracic segment, between T2–T7, was a contrast-enhancing mass (Fig. 1a). Histology revealed a discrete, cellular neoplasm with patchy glial fibrillary acidic protein (GFAP) immunoreactivity (Fig. 1d, inset), with small bland oval nuclei and thin, hair-like processes, reminiscent of pilocytic astrocytoma (Fig. 1d). Rosenthal fibers (RF) and eosinophilic granular bodies (EGB) were absent. Mitotic activity was inconspicuous, but Ki67 labeling indices (LI) were moderately elevated (approaching 15% in certain foci). Focal glomeruloid vasculature was present, but there was no necrosis. The tumor was initially considered to be a pilocytic astrocytoma, but some areas were vaguely palisaded, with irregular collections of synaptophysinimmunoreactive (Fig. 1f) tumor cells, showing early rosette formation (Fig. 1d). No lumen-containing true ependymal rosettes or perivascular pseudorosettes were identified. Neuronal differentiation was further supported by reactivity for neurofilament (NF) antisera, but there was no chromogranin expression. Since complete resection was not possible, eight courses of chemotherapy were offered. The lesion was been stable after 57 months of follow-up. The second case is that of an 8-year-old boy, who presented with back pain of 8-month duration, lower extremity weakness, associated increased tone, and myoclonus on the right side. The MRI showed a cystic mass in the thoracic spine associated with a syrinx (Fig. 1e). A gross total resection of the tumor was successfully performed in two sittings. The tumor was morphologically very similar to that of case 1, but also showed more distinct synaptophysin (Fig. 1g) and NF-immunoreactive (Fig. 1h) ‘neuronal’ islands consistent with neurocytic rosettes (Fig. 1f). A few cell nuclei in the rosettes were also positive for neuronal nuclear antigen (NeuN). A background of GFAP-positive piloid glial elements was noted, and these areas showed mild increase (2.8%) in Ki-67 LI (Fig. 1f, inset). In the subsequent resection, the tumor showed areas resembling pilocytic astrocytoma, with rare RF and EGB. The patient is clinically doing well after 1 year of follow up, although there is radiological suggestion of a small area S. Syed AE R. Raghavan (&) Department of Pathology and Human Anatomy, Loma Linda University Medical Center, 11234 Anderson St, Loma Linda, CA 92354, USA E-mail: rraghavan@ahs.llumc.edu Tel.: +1-909-5584398 ext 46885 Fax: +1-909-5584113