Mixed neuronal-glial tumor in the temporal lobe of an infant: a case report
© Yano et al.; licensee BioMed Central Ltd. 2013
Received: 30 April 2013
Accepted: 15 September 2013
Published: 2 October 2013
Tumors that arise in the temporal lobes of infants and spread to the neural system are limited to several diagnoses. Herein, we present an infantile case of a temporal tumor showing neuronal and glial differentiation.
The patient was a 9-month-old boy with low body weight due to intrauterine growth retardation. At 9 months after birth, he presented partial seizures. Computed tomography scanning revealed a mass (35 * 40 mm) in the left temporal lobe. Isointensity was noted on magnetic resonance T1-weighted images and fluid attenuation inversion recovery images. The tumor was heterogeneously enhanced with gadolinium. Positron emission tomography showed high methionine uptake in the tumor. During surgery, the tumor, which was elastic and soft and bled easily, was gross totally resected. A moderately clear boundary was noted between the tumor and normal brain parenchyma. Histologically, the tumor mainly comprised a ganglioglioma-like portion and short spindle cells at different densities. The former was immunohistochemically positive for some kinds of neuronal markers including synaptophysin. The spindle cells were positive for glial fibrillary acidic protein, but desmoplasia was not observed.
The tumor contained both neuronal and glial elements; the former were the main constituents of the tumor and included several ganglion-like cells. Because neuronal elements gradually transited to glial cells, a mixed neuronal-glial tumor was diagnosed.
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KeywordsNeuronal tumor Glioneuronal tumor Mixed tumor Temporal tumor Infant Epilepsy
Tumors that arise in the temporal lobes of infants and spread to the neural system include desmoplastic infantile ganglioglioma (DIG), pleomorphic xanthoastrocytoma (PXA), neuroblastoma (NB), and extraventricular neurocytoma (EVN). Herein, we present a case of a temporal tumor that spread to the neural system and discuss the tumor diagnosis in light of the clinical course, radiological findings, and histopathological findings.
Formalin-fixed, paraffin-embedded tissue sections were examined via hematoxylin-eosin staining and immunohistochemistry. The primary antibodies and dilutions in buffer were as follows: mouse monoclonal anti-synaptophysin (Syn) antibody (1:50; Millipore), monoclonal anti-neurofilament protein (NFP) antibody (1:150; Dako), monoclonal anti-neuronal nuclear antigen (NeuN) antibody (1:100; Millipore), mouse monoclonal anti-tubulin, βIII isoform (TuJ1) antibody (1:200; Millipore), mouse monoclonal anti-glial fibrillary acidic protein (GFAP) antibody (1:500; Dako), rabbit polyclonal anti-olig 2 antibody (1:100; IBL), mouse monoclonal anti-isocitrate dehydrogenase (IDH)1 R132H antibody (1:20; Dianova), and monoclonal anti-Ki-67/MIB-1 antibody (1:50; Dako). For all antibodies, antigen retrieval was performed by autoclaving (121°C, 15 min). An Envision kit (Dako) provided secondary antibodies conjugated to dextran polymer and hydrogen peroxidase, and 3,3-diaminobenzidine was used as the chromogen. Silver impregnation was performed according to a previously described method of silver staining .
In summary, the tumor contained both neuronal and glial elements. The neuronal elements were the main constituents of this tumor and included several ganglion-like cells of different shapes. Because neuronal elements gradually transited to glial cells, a mixed neuronal-glial tumor was diagnosed.
The tumor in the present case was considered to have both neuronal and glial elements, according to the results of immunohistochemical and EM analyses. Especially, neuronal differentiation was observed primarily as presented in the immunohistochemistry for some kinds of neuronal markers. DIG, PXA, NB and EVN are possible diagnoses for a tumor with both neural and glial differentiation.
DIGs are rare primary neoplasms that account for 0.5–1.0% of all intracranial tumors . DIG is a desmoplastic supratentorial neuroepithelial tumor that develops in patients whose ages range from 2 months to 59 years and occurs slightly more often in male individuals [3–6]. The large majority of these patients present with DIG within the first year of life . Most patients with DIG present with new onset seizures [2, 5, 6], with or without focal neurological signs such as hemiparesis. Increased intracranial pressure and lethargy might be the only findings . CT scans and MR images show large cystic tumors with enhancing solid components [6–9]. The frontal and temporal lobes are the most common sites of occurrence [2, 6, 7], wherein the tumor usually abuts the meningeal surface  and attaches to the dura. The tumors are firm and avascular with a dense desmoplastic component. There is no connection to the ventricular system. Microscopically, DIG shows evidence of glial and ganglionic differentiation, accompanied by an extreme desmoplastic reaction. In the present case, DIG was a possible differential diagnosis; however, no desmoplasia was histologically demonstrated. Radiological findings in this case did not show a cystic tumor, but rather a solid tumor that was exposed to the surface of the temporal lobe. Accordingly, we disregarded the diagnosis of DIG.
Secondary, PXA was also a possible diagnosis in the present case. These tumors occur most often in the temporal lobes of children or young adults [11–14], and associated seizures occur in up to 78% of cases . PXA usually presents as a cyst with a superficially situated mural nodule. However, Yu et al. reported 8 solid-type cases out of 19 total PXA cases . Microscopically, considerable pleomorphism, including spindle cells that transition through plump and/or polygonal cells to multinucleated giant cells, is observed. Endothelial proliferation and necrosis are absent. There have been reports of neuronal differentiation in PXA, according to immunohistochemical analysis [16–19]. Additionally, there have been several reports about the composition of PXA and ganglioglioma (PXA-GG) [20–22]. Sugita et al. summarized 17 cases of PXA-GG in which the patient ages ranged from 9 to 82 years. PXA-GG has not been reported in patients less than 1 year of age, as was the case for our patient. Thus, PXA could present with a divergent differentiation, as seen in the present case . However, higher cellularity, dominant neuronal differentiation, and fewer pleomorphic findings of multinucleated giant cells noted in this case were different from the common type of PXA. For these reasons, we disregarded the diagnosis of PXA.
In recent years, there have some reports of molecular analyses associating with glioma development or progressions. It was reported that RTEL1 tagging single-nucleotide polymorphisms (SNPs) & haplotypes were identified to be associated with glioma development . Furthermore, epidermal growth factor receptor and methylguanine-DNA methyltransferase (MGMT) promotor hypermethylation were reported to be associated with histological transformation and recurrence of gliomas. It seems like that the genetic alterations are early events in the development of glioma . It is possible that these molecular markers may help the diagnosis of low grade glioma.
Cerebral NB, a rare embryonal tumor, was also considered a possible diagnosis. These tumors usually arise in the frontotemporal region of children and often occur early in the first decade of life. The incidence of NB in Mexican children was reported to be 3.8 per 1,000,000 children/year; the incidence of NB was the highest in children under 1 year of age, followed by those between 1 and 4 years of age (18.5 and 5.4 per 1,000,000 children/years, respectively) . Histologically, homogenous and highly cellular arrangements with round to ovoid and hyperchromatic nuclei are observed. Varying numbers of Homer Wright rosettes are characteristic of these tumors. Rhythmic nuclear palisading, which produces parallel arrangements of cellular groups, might be observed. Neuronal differentiation can be detected by immunohistochemistry for neuronal markers such TuJ1, neurofilaments, and synaptophysin; however, glial differentiation is not demonstrated. In the present case, the rhythmic nuclear palisading pointed to this possible diagnosis; however, we disregarded it because of the presence of positive GFAP expression.
EVN was also a potential diagnosis. We previously reported a case of a 26-year-old woman who presented with atypical EVN, in which glial and neuronal differentiation was demonstrated by immunohistochemical analysis . Histologically, EVN shows an isomorphous population of small cells with perinuclear halos that are arranged against a neuropil background. Ganglion-like cells might be intermixed with the neurocytic elements . However, the patient in the present case had only a small number of oligodendroglioma-like halos in a limited portion. Because neurocytomas typically affect young adults, this was not applicable to the patient in our case with regard to the age of onset. Accordingly, we disregarded this diagnosis.
We emphasized that the histological and EM study demonstrated both neuronal and glial differentiation in the present case. The observations of the present case did not completely correspond with any differential diagnosis with regard to epidemiological, radiological, and histological findings. This is a rare infantile case report of a tumor that consisted mainly of neuronal-glial tumor cells without desmoplasia.
Written informed consent was obtained from the patient’s parents prior to the publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Neuronal nuclear antigen
Tubulin, βIII isoform
Glial fibrillary acidic protein
Desmoplastic infantile ganglioglioma
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