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Table of Contents    
CASE REPORT
Year : 2021  |  Volume : 69  |  Issue : 6  |  Page : 1808-1812

Tectal Rosette-Forming Glioneuronal Tumor – A Case Report Focusing on a Possible Role for Radiotherapy in Inoperable Tumors


1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi, India
3 Department of Neuroradiology, All India Institute of Medical Sciences, New Delhi, India
4 Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India

Date of Submission03-Jan-2019
Date of Decision18-Mar-2020
Date of Acceptance09-Jul-2020
Date of Web Publication23-Dec-2021

Correspondence Address:
Dr. Vaishali Suri
Departments of Pathology, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.333466

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 » Abstract 


Background: Rosette-forming glioneuronal tumor (RGNT) is a rare and distinctive glioneuronal tumor. Although surgical excision is considered the standard treatment for these slow growing WHO Grade I tumors, gross-total resection is achieved in less than 50% of RGNTs due to its localisation amidst vital structures. With very few cases with long term follow-up reported, there is limited knowledge of the natural clinical course and the role of radiotherapy in inoperable RGNTs.
Case Description: A previously well 26-year old male, presented with long standing headache, increasing gait instability and fainting episodes. Imaging revealed a tectal plate mass with hydrocephalous. An endoscopic third ventriculostomy and biopsy was done, revealing RGNT. He received radiotherapy with a curative intent. The patient remained neurologically stable for 4 years. Follow-up imaging done after 4 years showed decrease in tumor size.
Conclusions: The current case highlights a role for radiotherapy in RGNTs occurring in surgically challenging sites.


Keywords: Radiotherapy, RGNT, tectum
Key Message: RGNT is a rare CNS tumour with indolent course.


How to cite this article:
Nambirajan A, Sharma MC, Giridhar P, Khanna G, Garg A, Sharma R, Mallick S, Gupta S, Suri V, Parambath H. Tectal Rosette-Forming Glioneuronal Tumor – A Case Report Focusing on a Possible Role for Radiotherapy in Inoperable Tumors. Neurol India 2021;69:1808-12

How to cite this URL:
Nambirajan A, Sharma MC, Giridhar P, Khanna G, Garg A, Sharma R, Mallick S, Gupta S, Suri V, Parambath H. Tectal Rosette-Forming Glioneuronal Tumor – A Case Report Focusing on a Possible Role for Radiotherapy in Inoperable Tumors. Neurol India [serial online] 2021 [cited 2022 Jan 19];69:1808-12. Available from: https://www.neurologyindia.com/text.asp?2021/69/6/1808/333466




First referred to as 'Dysembryoplastic neuroepithelial tumor (DNT) of the cerebellum' and later identified as a distinct entity by Komori et al. in 2002,[1] 'rosette-forming glioneuronal tumor of the fourth ventricle' was introduced as a distinct entity in the World Health Organisation (WHO) 2007 classification of central nervous system (CNS) tumors. In addition to the fourth ventricle, RGNTs have been reported to occur in other midline locations including tectal plate, pineal gland, pons, thalamus and spinal cord leading to truncation of its nomenclature to 'rosette-forming glioneuronal tumor' (RGNT) in the current WHO classification.[2] Although they are slow growing, WHO grade I tumors, they are surgically challenging due to their frequent localisation around the brain stem, and are associated with a high incidence of debilitating post-operative neurological deficits.[3] The assessment of risk-benefit ratio of surgery and evaluation of alternate treatment regimens is required. However, the limited understanding of the long-term biological behaviour and its rarity hinders systematic assessment of treatment response. We present a patient with this rare entity who was treated with radiotherapy following a biopsy. He has remained neurologically stable over the follow-up duration of four years.


 » Case Summary Top


A 26-year-old male, previously well, presented with chronic headache for five years, with increasing severity for the last 6-months, associated with urinary incontinence and fainting episodes. No sensory or motor or cranial nerve deficits were detected on examination. Magnetic resonance imaging (MRI) revealed a heterogeneously enhancing solid-cystic mass in the tectal plate with associated hydrocephalous [Figure 1]a and [Figure 1]b. The patient underwent endoscopic third ventriculostomy and biopsy from the tectal plate glioma.
Figure 1: Radiological features and details of radiotherapy: Magnetic resonance imaging (MRI) revealed a mass in the tectal plate that was T2-hyperintense (a) and showed no contrast enhancement in axial contrast enhanced T1-weighted images (b). (c) Fused MR – CT image for target delineation. T1 weighted image taken for fusion; (d) Dose colour wash for 50.4 Gray (prescribed at 95% isodose) in a 3D CRT plan

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Histopathology revealed two distinct areas: a predominant glial component resembling a pilocytic astrocytoma composed of spindle shaped astrocytic tumor cells in a fibrillary background, and a neurocytic component composed of uniform neurocytic cells forming rosettes in a microcystic mucinous matrix. Microcalcifications were noted. Necrosis, mitoses, Rosenthal fibres, eosinophilic granular bodies or ganglion cells were not seen. Neuronal component was immunopositive for synaptophysin, MAP-2, beta tubulin and Neu-N. Glial fibrillary acidic protein (GFAP) was immunopositive in the fibrillary glial component. Immunostaining for IDH-R132H, p53, epithelial membrane antigen, and H3k27m-mutant specific antibodies was negative. There was no loss of ATRX (alpha thalassemia/mental retardation syndrome X-linked) expression in tumor cells. MIB-1 proliferation index was low (<1%). A final diagnosis of RGNT, WHO Grade I was rendered [Figure 2].
Figure 2: Histopathology of rosette forming glioneuronal tumors: Biphasic tumor composed of a predominant glial component and a neuronal component harbouring chunky calcification (a, Hematoxylin and eosin, x40); Neuronal component showing microcystic change (arrow, b, H and E, x100) and is composed of small neurocytic cells forming rosettes; glial fibrillary acidic protein positive glial component (c, IHC, x200); synaptophysin positive neuronal component (d, IHC, x400)

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Post-operatively, he developed transient bilateral facial nerve palsy and cerebrospinal fluid leak from the craniotomy site. Lumbar drain was placed and patient was stabilised. A multidisciplinary consensus decision was taken to treat the patient with radiation of conventional fractionation. A dose of 50.4 Gray in 28 fractions was administered over five and half weeks. The patient was immobilised in supine position with neck extended by a head rest in a thermoplastic mask. Contouring was done with MR-CT fusion. Clinical target volume (CTV) included the gross tumour with a 1 cm isotropic margin. A 0.3 cm isotropic margin to the CTV was given to form the planning target volume (PTV). Planning was done on the pinnacle planning system version 8.0 with three fields. The target volumes, dose colour wash and dose volume histograms are shown in [Figure 3]. The patient was treated with inter-fraction image guidance of cone beam computed tomography. The patient tolerated the treatment well with only grade 1 skin toxicity as a documented side effect. At 4 years post treatment, the patient is neurologically stable without any deficits with decrease in the size of the tumor.
Figure 3: Details of radiotherapy (a) Fused MR – CT image for target delineation. T1 weighted image taken for fusion; (b) Dose colour wash for 50.4 Gray (prescribed at 95 % isodose) in a 3D CRT plan; (c) Differential dose volume histogram (DVH) of plan; (d) Cumulative DVH of plan

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 » Discussion Top


RGNT is a rare WHO Grade I glioneuronal tumor, with <200 cases reported in literature.[4] They are diagnosed at a mean age of 26 years (ranging from 2 years to 84 years) and lack significant gender predilection.[2] They are predominantly located within the fourth ventricle or in the cerebellum (~70%), with tectal plate/pineal region being the second commonest reported location (~10%).[2] The biphasic histology comprised of neuronal and glial components is characteristic, however, may be missed in biopsies, leading to misdiagnosis. Similar biphasic differentiation can also be seen in papillary glioneuronal tumor (PGNT), diffuse leptomeningeal glioneuronal tumor (DL-GNT) and glioneuronal tumor with neuropil-like islands (GTNI). Correlating with clinical and radiological features along with relevant molecular analysis will aid in accurate diagnosis [Table 1]. RGNTs are postulated to arise from a common glial-neuronal precursor originating from the subependymal plate as evidenced by OLIG2 expression.[3],[5] A recent study lent support to this hypothesis by demonstrating similar mutation profiles in separately microdissected glial and neuronal components of three RGNTs.[5] The two most commonly identified mutations, detected in ~ 44-47% of RGNTs tested, occurs in the FGFR1 and PIK3CA genes respectively,[5] however, potential therapeutic targeting of these mutations has not been explored.
Table 1: Histological differential diagnoses of rosette-forming glioneuronal tumors (RGNTs) 2

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RGNTs are indolent tumors with a good prognosis. Adverse events in the form of increasing tumor size, tumor dissemination, recurrence or tumor related deaths are rare, reported in ~8% of all RGNTs.[4] They have been primarily treated by surgical resection, with gross total (GTR) and subtotal resection (STR) achieved in ~ 50% and ~ 26% of reported cases, respectively.[4] While tumors resected partially or only biopsied do appear to have an significantly increased risk for progression,[4] recurrence rates are not significantly different between tumors that undergo GTR or STR, leading some authors to recommend conservative resection to minimise postoperative neurological deficits.[3],[4] Younger age at presentation and purely solid radiology are other risk factors for post-surgical recurrence.[4] Histological progression to higher grade malignancy is uncommon during recurrence.[4]

Tumor resection is not feasible in at least one-fourth of all RGNT patients, especially in those located in the brain stem. Hence, there is a need to evaluate alternate treatment modalities. Literature review identified 6 patients of RGNT [Table 2] who had received adjuvant radiotherapy (RT) or chemotherapy (CT). CT/RT was administered usually a second line therapy during tumor progression,[3],[6],[7] and rarely as an adjuvant therapy following subtotal resection[1],[8] or biopsy.[9] Except for one patient who died due to radiation necrosis,[1] 3 patients who received RT were neurologically stable for follow-up durations ranging from 6 months to 4 years,[3],[7],[9] with one patient with a hypothalamic RGNT also showing decrease in tumor size.[7] The lack of progression for 4 years with decrease in tumor size in our patient who received radiotherapy with curative intent following biopsy suggests a potential role for RT in the management of inoperable RGNTs, although one must bear in mind that there are exceptional records of RGNT patients exhibiting a stable clinical course for up to 9 years in the absence of any therapeutic intervention.[10] We chose to treat our patient and not observe him as he presented with fainting episodes that affected his fitness to continue work. Currently, four years following radiotherapy, the patient is stable without neurological deficits and has been able to return to work.
Table 2: Clinical characteristics of RGNT patients treated with radiotherapy or chemotherapy including the current case

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To conclude, RGNTs are low grade glioneuronal tumors that are surgically challenging due to their localisation amidst vital anatomical structures. Their extreme rarity precludes systematic validation of alternate treatment regimens, including RT. Multi-institutional collaborative studies with uniform diagnostic criteria and long-term follow-up are required to accurately understand the natural history of these tumors and devise appropriate treatment strategies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Komori T, Scheithauer BW, Hirose T. A rosette-forming glioneuronal tumor of the fourth ventricle: Infratentorial form of dysembryoplastic neuroepithelial tumor? Am J Surg Pathol 2002;26:582-91.  Back to cited text no. 1
    
2.
Hainfellner JA, Giangaspero F, Rosenblum MK, Gessi M, Preusser M. Rosette-forming glioneuronal tumor. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system (Revised 4th ed.). Lyon, IARC; 2016. p. 150-1.  Back to cited text no. 2
    
3.
Zhang J, Babu R, McLendon RE, Friedman AH, Adamson C. A comprehensive analysis of 41 patients with rosette-forming glioneuronal tumors of the fourth ventricle. J Clin Neurosci 2013;20:335-41.  Back to cited text no. 3
    
4.
Yang C, Fang J, Li G, Li S, Ha T, Wang J, et al. Histopathological, molecular, clinical and radiological characterization of rosette-forming glioneuronal tumor in the central nervous system. Oncotarget 2017;8:109175-90.  Back to cited text no. 4
    
5.
Kitamura Y, Komori T, Shibuya M, Ohara K, Saito Y, Hayashi S, et al. Comprehensive genetic characterization of rosette-forming glioneuronal tumors: Independent component analysis by tissue microdissection. Brain Pathol 2018;28:87-93.  Back to cited text no. 5
    
6.
Ellezam B, Theeler BJ, Luthra R, Adesina AM, Aldape KD, Gilbert MR. Recurrent PIK3CA mutations in rosette-forming glioneuronal tumor. Acta Neuropathol 2012;123:285-7.  Back to cited text no. 6
    
7.
Yamamoto T, Matsubara T, Satomi K, Sakamoto N, Matsuda M, Muroi A, et al. Rosette-forming glioneuronal tumor originating in the hypothalamus. Brain Tumor Pathol 2015;32:291-6.  Back to cited text no. 7
    
8.
Morris C, Prudowsky ZD, Shetty V, Geller T, Elbabaa SK, Guzman M, et al. Rosette-forming glioneuronal tumor of the fourth ventricle in children: Case report and literature review. World Neurosurg 2017;107:1045.e9-16.  Back to cited text no. 8
    
9.
Sharma P, Swain M, Padua MD, Ranjan A, Lath R. Rosette-forming glioneuronal tumors: A report of two cases. Neurol India 2011;59:276-80.  Back to cited text no. 9
[PUBMED]  [Full text]  
10.
Haryu S, Saito R, Kanamori M. Rosette-forming Glioneuronal tumor: Rare case presented with spontaneous disappearance of contrast enhancement. NMC Case Rep J 2015;2:65-7.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

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