Tetraventricular Atypical Central Neurocytoma

Accepted Manuscript Tetraventricular Atypical Central Neurocytoma - Case Report Vikas Singh, MCh, Ashwin Borkar, MCh, Aliasgar Moiyadi, MCh, Prakash Shetty, MCh PII:

S1878-8750(18)32540-3

DOI:

https://doi.org/10.1016/j.wneu.2018.10.233

Reference:

WNEU 10677

To appear in:

World Neurosurgery

Received Date: 18 August 2018 Revised Date:

29 October 2018

Accepted Date: 31 October 2018

Please cite this article as: Singh V, Borkar A, Moiyadi A, Shetty P, Tetraventricular Atypical Central Neurocytoma - Case Report, World Neurosurgery (2018), doi: https://doi.org/10.1016/ j.wneu.2018.10.233. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Title: Tetraventricular Atypical Central Neurocytoma - Case Report

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Case Report

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Vikas Singh 1 , MCh ; Ashwin Borkar 2, MCh; Aliasgar Moiyadi 1 , MCh; Prakash Shetty 1, MCh.

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1- Neurosurgical Services, Department of Surgical Oncology, Tata Memorial Centre, Mumbai, India

Corresponding Author

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Vikas Singh

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2- Department of Neurosurgery, Associate consultant, Artemis Hospital, New Delhi.

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Fellow, Division of Neurosurgical oncology Department of Surgical Oncology Tata Memorial Centre,

Parel, Mumbai 400012 [email protected] +91-9594883899

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Key words – Central Neurocytoma, Atypical, Tetraventricular

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Tetraventricular Atypical Central Neurocytoma – Case Report

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Abstract Background: Central neurocytomas are benign tumors accounting for < 0.5% of all intracranial tumours. They are usually intraventricular, the commonest site being the lateral

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ventricles and are associated with good prognosis if they are completely resected surgically.

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Case and Description: We report a case of middle aged lady who was evaluated for recent onset headache and Magnetic resonance imaging (MRI) brain was suggestive of solid-cystic intraventricular mass spanning all the ventricles. Patient underwent subtotal excision of the mass with intraoperative neuromonitoring. Histopathology was suggestive of atypical

operative deficts.

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neurocytoma. Patient had complete neurological recovery in spite of immediate post-

Conclusion: Gross total resection should be the goal in all patients with central neurocytoma

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but it may be limited due to proximity to eloquent areas especially in large tumours. Intraoperative neuro-monitoring plays pivotal role in maximal safe resection of such large

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tumours. Tetraventricular atypical central neurocytoma is a very rare entity and this could be, to the best of our knowledge only the second reported case.

Key words – Central neurocytoma, Atypical, Tetraventricular

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Introduction

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Neurocytomas are benign tumours of the central nervous system (CNS) which predominantly occur in young adults and generally have a favourable outcome. They are typically located in the lateral ventricles in the region of foramen Monroe (central

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neurocytoma [CN]) or within the brain parenchyma (extraventricular neurocytoma). Atypical neurocytomas are neurocytomas with a MIB-1 LI >2% with/without anaplastic features. 1, 2

with classical neurocytomas.2,

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They have been noted to have worse clinical outcome and higher recurrence rate compared Inspite of the benign nature of the tumour, spinal

dissemination and malignant transformation has also been described.4,

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Here, we report a

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case of atypical neurocytoma with unusual radiological features.

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Case report

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We report a case of 32 year female who was seen with complaints of headache since 2 months. Computerized tomography (CT) brain was suggestive of intraventricular solid-cystic mass with calcifications. MRI brain [Figure 1 A,B] revealed a intraventricular solid cystic

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mass with epicentre in the body of the left lateral ventricle with extension into the third ventricle through foramen of Monroe with further extension into fourth ventricle via the

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aqueduct. Further it was seen to extend anteriorly into the supra sellar cistern and posteriorly through the pineal and suprapineal recesses into the quadrigeminal cistern expanding it. The mass was purely intraventricular with iso-hypointense signals on T2 with no adjacent parenchymal involvement or altered signal intensity or spinal dissemination. The solid

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component showed areas of T1 hyperintensity suggestive of hemorrhagic changes with minimal post contrast enhancement. She underwent a left frontal craniotomy, transcortical, transventricular approach and subtotal excision of the intraventricular tumour with intra

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operative neuromonitoring. The tumor was necrotic, soft, and suckable with large areas of haemorrhage. It was removed from the left lateral and third ventricle and third

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ventriculostomy was also performed. The extension projecting into the fourth ventricle through the widened aqueduct was also delivered. There were 50% reductions in motor evoked potentials (MEP) on the right side intraoperatively while dissecting it from the lateral wall of the lateral ventricle. Subsequently the lower limb MEP improved but upper limb MEP remained reduced. Hence further resection was stopped and small sliver of tumour along the lateral wall and the great veins were left behind.

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Expectedly, the patient developed right hemiparesis. Post-operative MRI showed a small

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residual lesion in the lateral ventricle and posterior third ventricle with hydrocephalus (post external ventricular drain removal) which necessitated at ventriculo-peritoneal (V-P) shunt. Following the VP shunt patient was more alert and her right hemiparesis (3/5) improved. Histologically, the tumour was composed of sheets of monomorphic round to oval shaped

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cells (with focal areas of perinuclear halo) interspersed with branching thin-walled blood

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vessel and no identifiable mitotic activity. On immunohistochemistry, the tumour was positive for Neu N and synaptophysin; while focally positive for Glial fibrillary acidic protein (GFAP). The tumour was negative for chromogranin, epithelial membrane antigen and L1CAM. Surprisingly, MIB-1 labeling index was approximately 6-8% in the focal highest proliferating areas. [Figure 2] Based on these features a histological diagnosis of atypical

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neurocytoma was rendered. At follow up patient was conscious alert and ambulatory independently with right hemiparesis (4/5) .MRI brain showed residual disease with

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ependymal enhancement due to postoperative hemosiderin [Figure 3]. MRI Spine was not suggestive of metastatic disease. In view of residual disease and histological diagnosis of

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atypical neurocytoma, pt was advised radiotherapy. Patient subsequently underwent radiotherapy to partial brain (total dose 54Gy/30#) and is under follow up.

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Discussion 6

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Central neurocytoma was first introduced as a distinct entity by Hassoun et al1 in 1982.

They are benign intraventricular neuronal tumour with a favourable prognosis and account for approximately 0.25–0.5% of intracranial tumours. They are classified as a grade II brain

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tumor according to the recent 2016 World Health Organization classification .7

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Historically many of the central neurocytomas (CN) were regarded as intraventricular oligodendroglioma or ependymoma. CN are neuroepithelial tumour composed of uniform round cells with fibrillary areas, low proliferation rate and may show oligodendrogliomalike honeycomb architecture or perivascular pseudorosettes as observed in ependymomas.

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Calcifications may be seen in half of the patients and hemorrhage and necrosis are rare. However, with the advent of better immunohistochemical markers for neuronal differentiation has helped to delineate neurocytomas from their morphological mimics of for

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oligodendroglioma and clear cell ependymoma. They are usually immunoreactive

synaptophysin, anti-HU antibodies and NeuN while expression of chromogranin-A, neuro-

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fibrillary protein, and alpha-internexin is lacking. This immunoprofile helps to distinguish central neurocytoma from ependymoma. Ependymoma is synaptophysin- negative and more diffusely positive for GFAP than is central neurocytoma.8 Immuno-histochemical stain OLIG 2 helps in differentiating central neurocytomas (usually negative) from oligodendrogliomas.8 CN are not immunoreactive for the R132-mutant IDH1 gene product , and p53 expression is usually lacking.

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Some CN may show anaplastic histological features like atypia, increased mitosis, vascular proliferation and presence of necrosis. Such tumours are termed as atypical central neurocytoma. Also central neurocytomas with a Ki-67 proliferation index of > 2% or 3% is termed as atypical CN, even when there are no associated anaplastic histological features.1, 2

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Anaplastic histological features are not generally associated with poor prognosis. However, a

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mitotic count of > 3 mitoses per 10 high-power fields has been found to be a predictor of higher risk of recurrence.8 Rades et al. also has suggested that a MIB-1 LI score >3% is associated with an adverse outcome.5 In our case there were no anaplastic features but MIB index was 6-8%. High MIB index in presence of residual disease was considered to have high risk of recurrence and was advised adjuvant radiotherapy.

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CN are usually located in lateral ventricles around foramen of Monroe (50%) and less commonly can be seen in both lateral ventricles (15%), triventricular (15%) and isolated in third ventricle (5%). Tetra ventricular disease is extremely rare and till date only four cases

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have been reported in the literature (Table 1).9-12 Complete resection of these extensive

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tumors remain a surgical challenge. Akakin et.al in 2015 reported a case tetraventricular central neurocytoma with proliferation index of 4%. This was probably the first reported case of tetraventricular atypical neurocytoma

Generally transcortical-transventricular and transcallosal-transventricular routes are the most common surgical approaches for unilaterally located tumours in the anterior part of lateral ventricles. We attempted transcortical-transventricular approach because the tumor was 6

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asymmetrically located, along with neuromonitoring (direct cortical MEP) to maximize safe

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resection. Improvement in the MEP during the surgery after initial drop may suggest reversibility of the postoperative motor outcomes, as did occur in our case. Anticipated complications following the surgery were hydrocephalus and development of neurologic deficits both of which were seen in our case.

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Risk of hydrocephalus can be reduced with placement of external ventricular drain post

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operatively and performing a VP shunt if hydrocephalus persists on post-operative imaging. Use of Neuromonitoring during intraventricular surgeries help to minimise the risk of injury to corticospinal tracts especially in a setting of tetraventricular tumours thus minimizing the postoperative morbidity

Surgical resection is the preferred treatment for CN, along with adjuvant radiation therapy in

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cases of subtotal resection/residual disease.10 Local recurrence is common with subtotal resection and higher proliferation rates (>2-3%) are associated with shorter recurrence-free

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intervals.13 Maximum safe resection should be the goal followed by adjuvant radiotherapy in cases of residual disease or atypical CN to prolong recurrence free survival. In our case

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patient underwent subtotal resection as there was drop in MEP by 50% and necessitated postoperative radiotherapy. Even though it is a benign disease, risk of recurrence, spinal dissemination and malignant transformation remians5 even after complete treatment. Hence a close follow up is mandatory in patients with atypical histology with/without residual disease.

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Conclusion:

Maximal safe resection should be the goal in all patients and intraoperative neuro-monitoring

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plays an important role especially in such large tetraventricular tumours. This is probably the

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second case of a atypical tetraventicular central neurocytoma reported, treated with subtotal surgical resection with neuromonitoring and a good functional outcome at follow up. Microsurgical resection with multimodal neuro-physiological monitoring and subsequent adjuvant radiotherapy ensured an optimal outcome.

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Acknowledgement: We acknowledge the support of Dr. Epari Sridhar - department of

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Pathology, Tata Memorial Centre, Mumbai, in writing this case report

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Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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References

1. Fujimaki T, Matsuno A, Sasaki T, Toyoda T, Matsuura R, Ogai M, Kitanaka C, Asai

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A, Matsutani M, Kirino T. “Proliferative activity of central neurocytoma:

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measurement of tumour volume doubling time, MIB-1 staining index and bromodeoxyuridine labelling index,” J Neuro-Oncol, vol. 32, no. 2, pp. 103–109, 1997.

2. Soylemezoglu F, Scheithauer BW, Esteve J, Kleihues P, “Atypical central neurocytoma,” J Neuropathol Exp Neurol, vol. 56, pp. 551–556, 1997

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3. Sharma MC, Rathore A, Karak AK, Sarkar C, “A study of proliferative markers in central neurocytoma,” Pathology, vol. 30, no. 4, pp. 355–359, 1998.

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4. Eng DY, DeMonte F, Ginsberg L, Fuller GN, Jaeckle K. Craniospinal dissemination of central neurocytoma. Report of two cases,” J Neurosurg, vol. 86, no. 3, pp. 547–

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552, 1997

5. Rades D, Schild SE, Fehlauer F. “Prognostic value of the MIB-1 labeling index for central neurocytomas,” Neurology 2004, vol. 62, no. 6, pp. 987–989,

6. Hassoun J, Gambarelli D, Grisoli F, et al. Central neurocytoma: an electronmicroscopic study of two cases. Acta Neuropathol. 1982;56(2):151–156

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7. Louis DN, Ohgaki H, Wiestier OD, Cavenee WK, Ellison DW, Branger DF, Perry A WHO classification of Tumours of central Nervous system 2016. Revised 4 th edition. 156158 888.

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8. Vasiljevic A, Frangois P, Loundou A, Fevre- MontangeM, JouvetA, Roche PH (2012).

Pathol. 36(2):220-7. PMID: 22251941

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Prognostic factors in central neurocytomas: a multicenter study of 71 cases. Am J Surg

9. Roche PH, Malca S, Gambarelli D, Pellet W. Giant central neurocytoma with

2): 95-100

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tetraventricular and extra-axial extension. Case report. Acta Neurochir (Wien) 1995; 133 (1-

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10. Akin Akakin, Baran Yilmaz, Mustafa Kemal Demir, Ozlem Yapicier et al. Tetraventricular central neurocytoma: A rare presentation with imaging-pathologic

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correlation. J Neurosci Rural Pract. 2015 Oct-Dec; 6(4): 594–597

11. Jhawar SS, Nadkarni T. Pan ventricular neurocytoma. Asian J Neurosurg. 2015 Jan-Mar; 10(1): 60

12. Yasargil MG, von Ammon K, von Deimling A, Valavanis A, Wichmann W, Wiestler OD. Central neurocytoma: histopathological variants and therapeutic approaches. J Neurosurg. 1992 Jan; 76(1):32-7 10

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13. Choudhari KA, Kaliaperumal C, Jain A, et al. Central neurocytoma: multidisciplinary

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review. Br J Neurosurg. 2009; 23(6):585–595

Figure legends

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Figure 1 A – Axial T2 weighed MRI (a-d) showing solid cystic intraventricular mass with areas of hyperintensity of T1 (e-f)

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Figure 1B – Coronal T2 and Sagittal T1 weighed MRI (a-b) demonstrating the dilated ventricular system and tetraventricular extent of the tumor. Axial contrast enhanced images

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(c-d) showing minimal heterogeneous contrast enhancement. Contrast enhanced spine imaging (d-e) with no evidence of spinal metastasis. Figure 2 – Photomicrographs of the biopsy specimen. (a)- Hand E showing sheets of clear cells and monomorphic nuclei. Also seen are round to oval tumor cells with central nuclei. (b) – Immunopositive tumor cells. (c) – NeuN positive tumor cells. (d) – Synaptophysin positive tumor cells

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Figure 3 – Axial T1 (a), Axial and coronal T2 (b-d) showing VP shunt in situ along with

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enhancing residual disease along deep venous system.

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residual tumor along the great veins. Axial contrast images (d-e) showing minimally

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Author

1

Roche

Title et

al Giant

1995. [9]

Histology central neurocytoma with Central

tetraventricular

and

extra-axial Neurocyoma

extension. Case report.

Akakin et al. 2015. [10]

neurocytoma: A rare presentation with correlation.

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Jhawar et al.

Central

Neurocytoma

Histopathologic

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1992. [12]

Atypical Central

Neurocytoma

Central Neurocytoma

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Yasargil et. al.

imaging-pathologic

Pan ventricular neurocytoma

2015 [11]

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central

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Tetraventricular

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2

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Sr no

variants

: and

Central neurocytoma

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therapeutic approaches

Table 1- Tabular representation of tetraventricular central neurocytoma cases reported in past.

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Abbreviations MRI –Magnetic Resonance Imaging

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CN – Central Neurocytoma CNS – Central Nervous System

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CT - Computerized tomography

VP shunt - Ventriculo-peritoneal shunt

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GFAP - Glial fibrillary acidic protein

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MEP - Motor evoked potentials