Intraventricular glioneuronal tumor with disseminated lesions at diagnosis - a case report -
© Yano et al; licensee BioMed Central Ltd. 2011
Received: 8 October 2011
Accepted: 6 December 2011
Published: 6 December 2011
A 55-year-old man presented with a large tumor in his lateral ventricles. Magnetic resonance imaging revealed disseminated lesions in the third and fourth ventricles at the time of diagnosis. The patient underwent a partial removal of the tumor in the lateral ventricles. Histologically, the surgical specimens showed glioneuronal differentiation with ganglion or ganglioid cells, Rosenthal fibers, oligodendroglia-like honeycomb appearances, a spongy pattern, perivascular pseudorosettes, and many hyalinized blood vessels. Papillary structure was not observed. The neuronal component showed a moderately high labeling index of Ki-67/MIB-1. We diagnosed this tumor as atypical intraventricular glioneuronal tumor. The disseminated lesions disappeared after chemoradiation therapy with temozolomide, and the residual tumors in the lateral ventricles remained stable for 3 years after the surgery. We discuss the pathological diagnosis, therapy and clinical course with review of the literatures.
Keywordsdissemination glioneuronal tumor immunohistochemistry intensity-modulated radiation therapy temozolomide
Many types of brain tumors originate in the ventricles. For tumors with neuronal differentiation that occupy the anterior central part of the lateral ventricles in adults, central neurocytoma is typically the diagnosis . However, new entities of tumors with neuronal differentiation, which are rare, have been found in this region. Herein, we report an unusual case of a patient who had an atypical tumor with glioneuronal differentiation that arose from the lateral ventricles and that was already accompanied with intraventricular disseminations at the time of diagnosis. We discuss the rationale for the pathological diagnosis on the basis of the immunohistochemistry, the pathophysiology of the dissemination in the early clinical stages, and possible therapies for this tumor with a review of the literature.
Formalin-fixed, paraffin-embedded tissue sections were examined with hematoxylin-eosin (HE) staining and immunohistochemistry. The primary antibodies and their dilution with buffer were as follows: rabbit polyclonal anti-olig2 antibody (1:200; Millipore, Temecula, CA), polyclonal anti-vimentin antibody (1:200; Dako, Glostrup, Denmark), mouse monoclonal anti-glial fibrillary acidic protein (GFAP) antibody (1:500; Dako), mouse monoclonal anti-synaptophysin (Syn) antibody (1:50; Millipore), mouse monoclonal anti-tubulin, βIII isoform (TuJ1) antibody (1:200; Millipore), monoclonal anti-neuronal nuclear antigen (Neu-N) antibody (1:100; Millipore), monoclonal anti-microtubule associated protein-2 (MAP-2) antibody (1:100; Millipore), monoclonal anti-neuron-specific enolase (NSE) and monoclonal anti-Ki-67/MIB-1 antibody (1:50; Dako). Antigen retrieval using an autoclave (121°C, 15 min) was performed for all antibodies. An Envision kit (Dako) was used as a source of secondary antibodies conjugated to dextran polymer and hydrogen peroxidase, and 3,3-diaminobenzidine was used as the chromogen.
Results of the immunohistochemistry
For the residual tumor, the patient underwent intensity-modulated radiation therapy (IMRT) using helical tomotherapy, which consisted of 30 fractions and a median dose of 30.6 Gy. Temozolomide (TMZ: 150 mg/m2) was orally administered as a concomitant and adjuvant therapy following radiation therapy. Twelve months after the surgery, MRI with Gd revealed that the disseminated lesions in the lateral ventricles and fourth ventricle had disappeared. A small residual nodule remained in the tip of the left anterior horn. MRI with Gd showed that the residuum had remained stable for 30 months after the surgery. His memory disturbance gradually subsided, and his HDS-R scale improved to 25/30.
The tumor in this case exhibited components that showed perinuclear halos, which were suggestive of central neurocytoma. However, the tumor differed from central neurocytoma because it exhibited a small number of ganglion cells or ganglioid cells that were immunohistochemically positive for multiple neuronal markers. Additionally, the glial components observed in this tumor are uncommon in central neurocytomas. Although there is a possibility that these glial components might be trapped cell in the tumor, we regarded them as neoplastic cells because these components in the present case were too much as trapped cells. On the contrary, neuronal differentiation was not sufficient for central neurocytoma. Furthermore, the spongy pattern and abundant hyalinized vessels observed in this tumor were not consistent with the histological features of central neurocytoma. Hyalinized vessels are more frequently observed in papillary glioneuronal tumors (PGNT). However, the tumor of this case had less papillary structures and less ganglion cells than PGNTs, in which tumor cells are typically arranged around vessels, forming pseudopapillary structures .
Spongy patterns, Rosenthal fibers, hyalinized vessels, and honeycomb-like components have often been associated with PA . However, PA is usually found in younger people. Additionally, the lateral ventricle is not a typical site for PA, which usually derives from the optic chiasm, hypothalamus, thalamus, basal ganglia, cerebral hemispheres, or cerebellar hemispheres .
Along with PGNTs, rosette-forming glioneuronal tumors of the fourth ventricle (RGNT) were recently listed in the fourth edition of the World Health Organization Classification of Tumours of the Central Nervous System [4, 5]. It is notewothy that RGNTs have been reported to partly include similar features to PA, such as Rosenthal fibers, oligodendroglial components, and hyalinized vessels . The tumor of the present case may have been more similar to a RGNT rather than a PGNT because it exhibited PA-like features, a small amount of ganglion cells, and perivascular pseudorosettes that are unlikely in PGNTs . The average age of onset in RGNT is reported to be higher than that in PGNT [4, 6]. The present patient had another lesion in the fourth ventricle. However, we suggest that the lesion was a dissemination from the tumor of the lateral ventricle because of the tumor size and because of the patient's initial clinical symptoms. Thus, the fourth ventricle was not the primary site of the tumor in this case, which differs from RGNT cases.
The moderately high Ki-67 labeling index (LI) was another clue for the diagnosis of this tumor. The Ki-67 LI of ordinary glioneuronal tumors or central neurocytoma is less than 3%. The differential diagnoses were atypical central neurocytoma and PA with atypical features. Considering these histological variabilities of neuronal and glial component and the atypical histological findings, we finally diagnosed this case as an intraventricular tumor with atypical glioneuronal differentiation. According to Ishizawa et al. , there was a case of PGNT with proliferation of minigemistocytic component, which showed a high Ki-67 LI. This findings were considered to coincide with our case. However, it was reported that high Ki-67 LI in a case of PGNT was not nessesary associated with poor prognosis .
To the best of our knowledge, 11 cases of intracranial glioneuronal tumors (1 cases of PGNTs , 9 of malignant glioneuronal tumors  and 1 of RGNT ) presenting dissemination in the clinical course have been reported. There are also 3 cases of spinal cord glioneuronal tumors with neuropil-like islands presenting meningeal dissemination [12–14]. Javahery et al.  reported on a case of a 13-year-old girl with PGNT. She had a primary cystic lesion in the left frontal lobe, which was totally removed. However, 43 months after the initial surgery, the tumor relapsed adjacent to the primary site with dissemination to the pulvinar nucleus and the medial left thalamus, which disappeared with radiation therapy and concomitant temozolomide therapy. Varlet et al.  reported a summary of 9 cases with malignant glioneuronal tumors that exhibited dissemination with a median time to the event of 19 months after the initial treatment. Wang et al.  reported a case of 16-year-old girl with RGNT initially presenting intraventricular dissemination. She underwent a neuroendoscopic biopsy and postoperative radiotherapy. Accordingly, there were only 2 cases of intracranial glioneuronal tumors presenting with intraventricular dissemination at such an early time including our case. Attention may need to be paid to the dissemination in the case with glioneuronal tumor including the case of spinal cord origin.
Varlet et al.  reported that gross total resection of a malignant glioneuronal tumor was an independent and statistically significant prognostic factor. Additionally, they also stated that focal or craniospinal radiation therapy seemed neither to control local tumor growth nor to prevent dissemination of these tumors. Although our case underwent a partial resection of the tumor, the subsequent IMRT and adjuvant chemotherapy with temozolomide greatly reduced the residual tumors in the fourth ventricle and the anterior horn of the lateral ventricle. MRI with Gd demonstrated no recurrence of the residual small tumor 30 months after the surgery.
Following surgery, radiation therapy with concomitant administration of TMZ has recently become the standard therapy for malignant gliomas. As shown by the cases of Javahery et al.  and the present case, this therapy may also be effective for glioneuronal tumors.
This is the rare case of glioneuronal tumor to present intraventricular dissemination at diagnosis, which have a possibility of transitional form between glial and neuronal components. The case was successfully treated wih a possible reductive surgery followed by IMRT with administarion of TMZ.
Written informed consent was obtained from the patient for 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.
1 Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan
2 Pathology Division, Gifu University Hospital, Gifu, Japan
3 Chubu Medical Center for Prolonged Traumatic Brain Dysfunction, Department of Neurosurgery, Kizawa Memorial Hospital, Minokamo, Japan
List of abbreviations
Hasegawa's dementia scale
magnetic resonance imaging
fluid-attenuated inversion recovery Gd: gadolinium
glial fibrillary acidic protein
tubulin, βIII isoform
neuronal nuclear antigen
microtubule associated protein-2
intensity-modulated radiation therapy
papillary glioneuronal tumors
Rosette-forming glioneuronal tumors of the fourth ventricle.
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