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CASE REPORT
Year : 2019  |  Volume : 67  |  Issue : 5  |  Page : 1327-1330

Giant Cell-rich Tanycytic Ependymoma as Intramedullary Spinal Mass


1 Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication19-Nov-2019

Correspondence Address:
Dr. Kirti Gupta
Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.271272

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 » Abstract 

Intramedullary spinal cord tumors are rare neoplasms and harbour full spectrum of primary neoplasms as seen within the intracranial compartment. They include tumors with diverse pathologies, arising in both adults and children and pose considerable diagnostic challenge. The differentials at this site include wide ranging pathologies from benign, circumscribed pilocytic to diffuse astrocytoma, myxopapillary or tanycytic ependymoma and malignant diffuse midline glioma. Rare instances of glioneuronal tumors, pleomorphic xanthoastrocytoma have also been described at this location. H3K27M mutant diffuse midline high grade glioma is the new entry to this list in 2016 updated WHO classification. We describe the morphologic features of a diagnostically challenging intramedullary spinal cord tumor masquerading as a high grade lesion due its cellular composition and discuss its differentials. The report also emphasizes the role of already established and recently introduced immunohistochemical markers and other ancillary techniques as useful adjuncts in the diagnosis.


Keywords: Ependymoma, giant cell, Intramedullary tumors, spinal tumor, tanycytic
Key Message: Tanycytic ependymoma with abundant ploemorphic giant cells is a rare variety of intramedullary spinal cord tumor arising from the conus/filum terminale region. Microscopically, this variant consists of highly peomorphic cells with nuclear atypia presenting a scary picture. The prognosis seems good with complete excision.


How to cite this article:
Parkhi M, Gupta K, Singh A, Salunke P. Giant Cell-rich Tanycytic Ependymoma as Intramedullary Spinal Mass. Neurol India 2019;67:1327-30

How to cite this URL:
Parkhi M, Gupta K, Singh A, Salunke P. Giant Cell-rich Tanycytic Ependymoma as Intramedullary Spinal Mass. Neurol India [serial online] 2019 [cited 2019 Dec 8];67:1327-30. Available from: http://www.neurologyindia.com/text.asp?2019/67/5/1327/271272




Intramedullary spinal cord tumors (IMSCTs) account for 2% to 4% of all central nervous system (CNS) tumors, with ependymoma being the most common in adults while astrocytomas being most common in children and adolescents.[1] Other rare examples include ganglioglioma, hemangioblastoma, pleomorphic xanthoastrocytoma (PXA), primary CNS lymphoma, melanomas, and, rarely, metastasis from a primary tumor.[2] Overall, 15% of all primary intramedullary spinal tumors are ependymal in origin and include one of the three histopathologic subtypes: ependymoma, subependymoma, and myxopapillary ependymoma. Tanycytic ependymoma is an uncommon variant which preferentially arises at this location compared with other regions of the neuraxis.[3],[4],[5] It is characterized by elongated spindle-shaped, bipolar cells possessing thin eosinophilic fibrillary processes. It is thought that this variant most closely resembles primitive radial glia-like tanycytes distributed in the floor of the third ventricle, regions of the so-called circumventricular organs, and the spinal cord.[3],[6] Neoplastic cells usually do not exhibit anaplastic cytological features such as nuclear atypia or pleomorphism, and although it has been assigned for grade II lesions in the current 2016 World Health Organization (WHO) classification,[7] it is generally a slow-growing, non-invasive tumor that behaves like a grade I lesion. Rarely, it may contain widespread component of giant cells that has led to few reports in the literature as “giant cell-rich ependymoma.”[8],[9],[10] Similar example has been reported from the Indian subcontinent.[11] Despite the presence of pleomorphic giant cells, the prognosis has been relatively good in a few reported cases of giant cell ependymoma. We describe an interesting case offilum terminale/conus medullaris mass diagnosed as tanycytic variant of ependymoma replete with pleomorphic giant cells and discuss the differentials and the role of ancillary techniques helpful in reaching to the diagnosis.

A 50-year-old male presented with radiating back pain and paresthesia along the right L5-S1 roots for past 20 days. There was spasticity in both lower limbs on examination. He had good bladder and bowel control. Magnetic resonance imaging (MRI) revealed heterogeneously enhancing intradural lesion in conus–cauda (L1-2) level. The lesion was approached through L1-2 laminectomy. The tumor was fleshy gray with attachment to roots and conus could be partially excised. Post-operatively, he had no added deficits. His back pain and paresthesia improved and is doing well at 1-year follow-up. The resected tissue was fixed in 10%-buffered formaldehyde and paraffin embedded. Hematoxylin- and eosin-stained sections were used for diagnosis. For immunohistochemistry, 5-μm sections of a representative block were obtained. The following antibodies were used: glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), synaptophysin, NeuN, S100, BRAF VE1 for BRAF V600E mutation, H3K27me3 for detectingH3K27 mutant protein, and Ki-67. These were performed on Ventana, Biotek System, with appropriate positive and negative controls run concurrently. Briefly, paraffin sections were mounted on charged glass slides, air-dried overnight, and then deparaffinized. To enhance the immunostaining, a heat-induced epitope-retrieval procedure was performed. After incubation with blocking serum, sections were incubated with primary antibodies, followed by a biotinylated-polyvalent secondary antibody solution. Sections were then incubated with horseradish peroxidase–conjugated avidin-biotin complex, followed by 3,3-diaminobenzidine and hydrogen peroxidase. Microscopically, the fragments revealed a moderately cellular tumor consisting of oval to spindle-shaped cells against a fibrillary background [Figure 1]a. These cells formed compact and streaming cellular fascicles that loosely curved and intersected with each other [Figure 1]b. Nuclei displayed even distribution of chromatin with bipolar to multipolar fibrillary cytoplasmic processes. The most prominent finding was the presence of many atypical and pleomorphic giant cells distributed in loose clusters [Figure 1]c. Some of these monstrous cells demonstrated multilobation and multinucleation with few showing intranuclear cytoplasmic invagination [Figure 1]d. Mitosis as such was very low to almost absent. A minor population of cells with oval morphology present in sheets was also noted [Figure 2]a and [Figure 2]b. True ependymal rosettes were not discernible; however, occasional vague perivascular pseudo-rosettes were evident in some fragments. Few areas exhibited hemorrhage; however, there was no evidence of necrosis. No microvascular proliferation was noted. Rosenthal fibers or eosinophilic granular bodies were not identified. On immunohistochemistry, the entire population of tumor cells were diffusely and strongly positive for GFAP [Figure 2]c and [Figure 2]d. EMA revealed very occasional dot-like positivity in few cells, a characteristic feature of ependymoma [Figure 3]a. NeuN and synaptophysin were negative, thereby excluding the glioneuronal tumors including ganglioglioma. S100 was negative within the tumor cells. The cells were also negative for BRAF V600E mutant protein, thus ruling out a possibility of PXA which frequently harbor this mutation. H3K27M was also negative; thus, high-grade diffuse midline glioma is unlikely. Ki-67 labeling index was very low (<1%) [Figure 3]b and [Figure 3]c. Electron microscopy performed from formalin-fixed paraffin embedded (FFPE) sections revealed intercellular aggregates of microvilli alongwith intracytoplasmic intermediate filaments [Figure 4]a and [Figure 4]b. Other features typical of ependymal differentiation including zipper-like junctional complexes with desmosomes were not appreciated as the tissue preservation was compromised due to FFPE material.
Figure 1: (a) Low magnification shows cells arranged in diffuse sheets against a fibrillary background (hematoxylin and eosin [H and E]×100); (b) pleomorphic cells arranged in short fascicles (H and E ×400); (c and d) numerous bizarre and pleomorphic cells populating most of the tumor fragments (H and E ×1000)

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Figure 2: (a and b) Small subsets of cells with oval morphology present in sheets (a, H and E ×200, b, H and E ×400); (c and d) tumor cells were diffusely and strongly positive with GFAP (immunoperoxidase ×200 (c), ×400 (d)

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Figure 3: (a) Occasional dot-like positivity for EMA (arrow) (immunoperoxidase ×400); (b) very low Ki-67 labeling index (immunoperoxidase ×400); (c) tumor cells negative for synaptophysin, NeuN, S100, H3K27M, BRAF V600E (immunoperoxidase ×100)

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Figure 4: (a) Intracytoplasmic filaments corresponding to glial filaments (bold arrow) (original magnification ×3000, uranyl acetate with lead citrate); (b) intercellular aggregates of microvilli (bold arrow) (original magnification ×15000, uranyl acetate with lead citrate)

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IMSCTsare rare neoplasms, of which ependymoma constitutes the majority.[1] As true for any other intracranial site, the surgical pathology is best represented on radical resection specimen rather than a small biopsy. Limited sample size available for diagnosis makes these tumors diagnostically challenging. While immunohistochemistry has been time-tested useful adjunct to morphological diagnosis, the role of ultrastructural examination cannot be understated in challenging cases.

The differentials at this site include wide ranging pathologies from benign, circumscribed pilocytic to diffuse astrocytoma, myxopapillary or tanycytic ependymoma, ancient schwannoma, and malignant diffuse midline glioma. Rare instances of glioneuronal tumors, PXA, have also been described at this location. Ancient schwannoma and rarely pilocytic astrocytoma are known to exhibit sudden nuclear atypia and pleomorphism, with occasional mitotic figures. Diffuse positivity for S100 protein is typical of ancient schwannoma, which in the present case was negative. Pilocytic astrocytoma as such is a very rare presentation in this age group. PXA, though uncommon at this location, displays neoplastic astrocytes with xanthomatous cytoplasm against a coarse fibrillary background. Majority of these are enriched for BRAF V600E mutation, in the absence of isocitrate dehydrogenase (IDH) mutation.[7],[12] The present tumor was negative for BRAF V600E mutant protein, synaptophysin, and NeuN on immunohistochemistry. Ganglioglioma arising in the spinal cord are characterized by a biphasic cellular composition positive for both glial and neuronal markers.[13] H3K27M-mutant diffuse midline gliomas predominates not only in children but can also be seen in adults, with the most common locations being brain stem, thalamus, and spinal cord.[7] It is an infiltrative tumor with predominant astrocytic differentiation, mitotic activity, microvascular proliferation, and presence of necrosis. The absence of significant mitotic activity, microvascular proliferation, and necrosis excludes high-grade gliomas, morphologically. Moreover, H3K27me3 mutant protein was negative. Diffuse and strong GFAP expression in this case rules out the possibility of paraganglioma, adrenal carcinoma, urothelial carcinoma, epithelioid malignant peripheral nerve sheath tumors, and metastatic melanoma, as all these differentials considered can show presence of multinucleated giant cells morphologically. Most of these tumors are mitotically active with numerous mitotic figures. Rare examples of myxopapillary ependymoma exhibits solid fascicular growth pattern;[14] however, absence of both the characteristic papillary architecture and myxoid degeneration of the perivascular stroma excludes this tumor.

The present tumor shares morphological findings with two cases of giant-cell ependymoma of the filum terminale, which was documented by Zec et al. in 1996.[8] They hypothesized that the absence of perivascular pseudorosettes in giant-cell ependymoma might reflect the failure of the neoplastic cells in this tumor to elaborate perivascular processes. Vague pseudovascular rosettes formation was identified focally in the present case.

In conclusion, we present a rare case of tumor arising in filum terminale and conus medullaris, composed of spindle cells in fascicular pattern admixed with numerous giant cells featuring marked nuclear atypia and pleomorphism without any evidence of mitotic activity, microvascular proliferation, or necrosis. Immunoreactivity pattern aided in reaching to the final diagnosis of giant cell-rich tanycytic ependymoma, and ultrastructural features confirmed the ependymal nature of this tumor. Despite the worrisome morphological appearance, the prognosis is good with gross total excision.

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

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Chamberlain MC, Tredway TL. Adult primary intradural spinal cord tumors: A review. Curr Neurol Neurosci Rep 2011;11:320-8.  Back to cited text no. 1
    
2.
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Langford LA, Barre GM. Tanycytic ependymoma. Ultrastruc Pathol 1997;21:135-42.  Back to cited text no. 3
    
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Kawano N, Yagishita S, Oka H, Utsuki S, Kobayashi I, Suzuki S, et al. Spinal tanycytic ependymomas. Acta Neuropathol 2001;101:43-8.  Back to cited text no. 4
    
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Boccardo M, Telera S, Vitali A. Tanycytic ependymoma of the spinal cord. Case report and review of the literature. Neurochirurgie 2003;49:605-10.  Back to cited text no. 5
    
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Flament-Durand J, Brion JP. Tanycytes: Morphology and functions: A review. Int Rev Cytol 1985;96:121-55.  Back to cited text no. 6
    
7.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon: IARC Press; 2016. p. 106-11.  Back to cited text no. 7
    
8.
Zec N, De Girolami U, Schofield DE, Scott RM, Anthony DC. Giant cell ependymoma of the filum terminale. A report of two cases. Am J Surg Pathol 1996;20:1091-101.  Back to cited text no. 8
    
9.
Li JY, Lopez JI, Powell SZ, Coons SW, Fuller GN. Giant cell ependymoma-report of three cases and review of the literature. Int J Clin Exp Pathol 2012;5:458-62.  Back to cited text no. 9
    
10.
Shintaku M, Sakamoto T. Tanycytic ependymoma of the filum terminale with pleomorphic giant cells. Brain Tumor Pathol 2009;26:79-82.  Back to cited text no. 10
    
11.
Trivedi P, Gupta A, Pasricha S, Patel D. Giant cell ependymoma of a cervical spinal cord. Indian J Pathol Microbiol 2011;54:201-3.  Back to cited text no. 11
[PUBMED]  [Full text]  
12.
Schindler G, Capper D, Meyer J, Janzarik W, Omran H, Herold-Mende C, et al. Analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma. Acta Neuropathol 2011;121:397-405.  Back to cited text no. 12
    
13.
Gupta K, Orisme W, Harreld JH, Qaddoumi I, Dalton JD, Punchihewa C, et al. Posterior fossa and spinal gangliogliomas form two distinct clinicopathologic and molecular subtypes. Acta Neuropathol Commun 2014;2:18.  Back to cited text no. 13
    
14.
Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. WHO Classification of Tumours of the Central Nervous System. 4th ed. Lyon: IARC Press; 2016. p. 104-5.  Back to cited text no. 14
    


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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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