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NI FEATURE: FACING ADVERSITY…TOMORROW IS ANOTHER DAY! - LETTER TO EDITOR
Year : 2017  |  Volume : 65  |  Issue : 5  |  Page : 1134-1136

A case of clear cell ependymoma with bizarre aggressiveness: Are we underestimating its ferocity?


1 Department of Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Cytopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication6-Sep-2017

Correspondence Address:
Manjul Tripathi
Department of Neurosurgery, Nehru Hospital, 5th Floor, Post Graduate Institute of Medical Education and Research, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/neuroindia.NI_378_16

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How to cite this article:
Gupta K, Tripathi M, Gupta N, Ranganath S, Salunke P. A case of clear cell ependymoma with bizarre aggressiveness: Are we underestimating its ferocity?. Neurol India 2017;65:1134-6

How to cite this URL:
Gupta K, Tripathi M, Gupta N, Ranganath S, Salunke P. A case of clear cell ependymoma with bizarre aggressiveness: Are we underestimating its ferocity?. Neurol India [serial online] 2017 [cited 2019 Dec 12];65:1134-6. Available from: http://www.neurologyindia.com/text.asp?2017/65/5/1134/214048


Sir,

Clear cell ependymoma (CCE) is an uncommon aggressive histological variant of ependymoma with a propensity for recurrence, extraneural metastases, and morphological mimicry to other clear cell tumors.[1] Our case highlights its aggressive clinical behaviour, the histological mimics, the diagnostic dilemmas, the need for an early evaluation of the craniospinal axis, and the possible adjuvant radiotherapy that needs to be administered to the entire axis.

A 17-year old male patient presented to another hospital with complaints of headache characteristically representative of raised intracranial pressure (ICP) of one-year duration. His neurological examination was unremarkable except for papilledema. Magnetic resonance imaging (MRI) revealed a poorly marginated nodular enhancing lesion in the left parieto-occipital region (measuring 6 × 4 × 4 cm) with intraventricular extension and ependymal enhancement [Figure 1]a,[Figure 1]b,[Figure 1]c. The rest of the craniospinal evaluation was normal. The patient underwent a left parieto-occipital craniotomy with subtotal excision of the tumor [Figure 1]d. The histopathology was suggestive of CCE grade II. The patient did not consent for adjuvant focal radiotherapy. After a month, he presented with worsened headache, decrease in vision, and low backache. The repeat MRI disclosed a nodular enhancing lesion with partial confluence in the left parieto-occipital lobe, diffuse ependymal enhancement, and a midline shift of 7 mm. There was an additional 27 × 25 mm heterogeneously enhancing, solid-cystic mass lesion in the suprasellar region with intrasellar and third ventricular extension and hydrocephalus [Figure 1]e,[Figure 1]f,[Figure 1]g. The spinal MRI was unremarkable [Figure 1]h. A right-sided ventriculoperitoneal (VP) shunt was placed to relieve the raised ICP. Ventricular cerebrospinal fluid (CSF) and diagnostic lumbar CSF revealed the presence of malignant cells with an identical morphology. The patient had symptomatic improvement with CSF diversion. He was advised craniospinal irradiation. However, he rapidly deteriorated at home (secondary to the shunt obstruction) and soon succumbed to the disease within a 2-month duration.
Figure 1: (a) Contrast MRI Brain and (b) sagittal, (c) coronal T2 weighted images showing heterogeneously enhancing solid cystic lesion in left parietooccipital region with extension into left ventricular system. (d) Post operative CT scan head showing subtotal resection with residual intraventriculartumor. E; Follow up MRI brain (e) axial, (f) sagittal and (g) Coronal images showing recurrent lesion with a separate lesion in sellarsuprasellar location. (h) Contrast MRI lumbar spine showing normal scan with an incidental Tarlov cyst

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On pathologic evaluation, the tumor comprised of multiple cellular fragments of oval-to-polygonal cells arranged in compact sheets interrupted by blood vessels [Figure 2]a. In some of the fragments, a sharp interface with the brain parenchyma was identified [Figure 2]b. The cellular outlines were distinct with centrally situated nuclei and clear cytoplasm giving a honeycomb appearance [Figure 2]c and [Figure 2]d. Nuclei were relatively large and convoluted. Anaplastic features including necrosis, endovascular proliferation, and mitoses were also detected (mitotic activity 4–5/high power field [hpf]) [Figure 2]e and [Figure 2]f. No typical pseudorosettes or ependymal canals were identified [Figure 3]a and [Figure 3]b. The Ki-67 proliferative index was high [Figure 3]c. CSF smears depicted presence of tumor cells of similar morphology [Figure 3]d.
Figure 2: (a) Tumor cells arranged in sheets interrupted by blood vessels (H and E ×200); (b) Sharp borders at the interface with the brain parenchyma (H and E ×100); (c) Oval-to-round tumor cells with distinct outlines and abundant clear cytoplasm (H and E ×400); (d-f) Anaplastic features including mitotic figures [arrow] (d, H and E ×400), endothelial proliferation (e, H and E ×400), and necrosis (f, H and E ×100) were identified

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Figure 3: (a) Tumor cells immunoreactive with GFAP with perivascular accentuation (immunoperoxidase ×400); (b) Puntate, dot-like positivity for EMA (immunoperoxidase ×400); (c) Tumor cells expressing a high proliferative index on Ki-67 (immunoperoxidase ×400); (d) CSF smear positive for tumor cells (Papanicolaou stain ×400)

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In contrast to other variants of ependymoma, anaplasia is common in CCE. Unfortunately, the features of anaplasia, particularly “brisk mitotic activity” and “increased cell density,” remain elusive as there is no defined cut-off value and a clear consensus on the grading criteria is not well established.[1],[2],[3],[4] Furthermore, CCEs often do not demonstrate the typical perivascular pseudorosettes and are likely to be misdiagnosed. Their sharp borders and nuclear features are helpful in distinguishing them from other clear cell mimics. The immunoreactivity for glial fibrillary acidic protein (GFAP) with accentuation in the perivascular location and dot-like positivity for epithelial membrane antigen (EMA) are highly sensitive and specific.[2],[3],[4]

As CCEs have a tendency to recur despite therapy, it is imperative to distinguish this entity from its other histologic mimics.[1],[2],[3],[4],[5] Ependymomas from different regions of the brain comprise distinct molecular variants.[4] Although C11orf95-RELA [v-rel avian reticuloendotheliosis viral oncogene] fusions in a recent landmark paper were confirmed to be the driver mutations for supratentorial ependymoma with some of the mouse tumors showing the morphology of “supratentorial vascular variant,” the study did not make a distinction regarding other morphological variants of ependymoma.[4] Loss of DAL-1 locus on chromosome 18p has also been reported.[1] There is a striking frequency of gains of chromosome 1q and loss of chromosome 9 in CCE compared to other variants of ependymomas.[5]

The median age of presentation ranges from 24 to 36 years. There are no specific radiological features to differentiate CCE from other variants. Similar to other ependymomas, gross total surgical resection is the treatment of choice. Role of concurrent chemoradiotherapy is being actively explored. The progression-free survival and 5-year survival range from 20–34% and 19–75%, respectively. There are no specific guidelines for the evaluation and management of clear cell variants of ependymoma.[1],[2],[3],[4],[5]

Overall, approximately 5% of patients with ependymoma present with features of leptomeningeal dissemination at the time of diagnosis, more frequently with infratentorial ependymomas followed by intraventricular tumors.[6],[7] However, tumor spread to other intracranial spaces as well as their leptomeningeal spread is very uncommon.[1],[2],[3],[4],[5] In rare cases, extracranial metastasis (to the cervical lymph nodes and soft tissues of the neck) has also been reported. CCE is also known to invade dura and venous sinuses. Interestingly, in other reported series also, the leptomeningeal spread has been very rare.[1],[2],[3],[4],[5] Such an aggressive behaviour is especially noted in younger patients.

The epidemiological rarity, nonspecific clinicoradiological presentation, and histological mimicry of CCEs with other more common clear cell tumors make it a diagnostic and management-related challenge. Unlike other variants of ependymomas, patients of CCE should have an aggressive upfront evaluation of the craniospinal axis to rule out an early spread. In our opinion, gross total removal with adjuvant craniospinal irradiation should be considered to prevent any early recurrence and prolong survival.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

1.
Fouladi M, Helton K, Dalton J, Gilger E, Gajjar A, Merchant T, et al. Clear cell ependymoma: A clinicopathologic and radiographic analysis of 10 patients. Cancer 2003;98:2232-44.  Back to cited text no. 1
[PUBMED]    
2.
Kawano N, Yada K, Yagishita S. Clear cell ependymoma. A histological variant with diagnostic implications. Virchows Arch A Pathol Anat Histopathol 1989;415:467-72.  Back to cited text no. 2
[PUBMED]    
3.
Ellison DW, Kocak M, Figarella-Branger D, Felice G, Catherine G, Pietsch T, et al. Histopathological grading of pediatric ependymoma: Reproducibility and clinical relevance in European trial cohorts. J Negat Results Biomed 2011;31:7.  Back to cited text no. 3
    
4.
Pajtler KW, Witt H, Sill M, Jones DTW, Hovestadt V, Kratochwil F, et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades, and age groups. Cancer Cell 2015;27:728-43.  Back to cited text no. 4
    
5.
Rousseau E, Palm T, Scaravilli F, Ruchoux MM, Figarella-Branger D, Salmon I, et al. Trisomy 19 ependymoma, a newly recognized genetico-histological association, including clear cell ependymoma. Mol Cancer 2007;6:47.  Back to cited text no. 5
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6.
Benson R, Mallick S, Julka PK, Rath GK. Molecular predictive and prognostic factors in ependymoma. Neurol India 2016;64:279-86.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Gupta K, Salunke P. Understanding ependymoma oncogenesis: An update on recent molecular advances and current perspectives. Mol Neurobiol 2017;54:15-21.  Back to cited text no. 7
[PUBMED]    


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