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CASE REPORT
Year : 2012  |  Volume : 60  |  Issue : 1  |  Page : 96-99

Embryonal tumor with multilayered rosettes: Two case reports with a review of the literature


1 Department of Pathology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, Kerala, India
2 Department of Neurosurgery, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, Kerala, India
3 Department of Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute of Medical Sciences and Technology, Trivandrum, Kerala, India

Date of Submission24-Nov-2011
Date of Decision19-Dec-2011
Date of Acceptance25-Dec-2011
Date of Web Publication7-Mar-2012

Correspondence Address:
V V Radhakrishnan
Department of Pathology, SCTIMST, Trivandrum - 695 011, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.93614

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 » Abstract 

Embryonal tumor with multilayered rosettes (ETMR) is a well-recognized histopathological variant of primitive neurectodermal tumors of the central nervous system. This tumor depicts histopathological features that are common to both ependymoblastoma (EBL) and neuroblastoma. Here we report two pediatric cases of ETMR, one exhibiting dominant neuronal differentiation and the other with dominant glial differentiation, thereby expanding the previously known pathologic spectrum. The varying histological features, common morphologic diagnostic difficulties as well as variable postsurgical survival of this entity compared to similar embryonal tumors are highlighted.


Keywords: Embryonal tumor with abundant neuropil and true rosettes, embryonal tumor with multilayered rosettes, ependymoblastic rosette, ependymoblastoma, primitive neuroectodermal tumor


How to cite this article:
Neelima R, Easwer H V, Kapilamoorthy T R, Hingwala DR, Radhakrishnan V V. Embryonal tumor with multilayered rosettes: Two case reports with a review of the literature. Neurol India 2012;60:96-9

How to cite this URL:
Neelima R, Easwer H V, Kapilamoorthy T R, Hingwala DR, Radhakrishnan V V. Embryonal tumor with multilayered rosettes: Two case reports with a review of the literature. Neurol India [serial online] 2012 [cited 2019 Sep 22];60:96-9. Available from: http://www.neurologyindia.com/text.asp?2012/60/1/96/93614



 » Introduction Top


Embryonal neoplasms are a heterogeneous group of malignant neoplasms in the central nervous system (CNS). On the basis of their morphological, immunohistochemical and molecular genetic features, these tumors are broadly classified by the World Health Organization (WHO) classification of CNS tumors into medulloblastoma, atypical teratoid/rhabdoid tumor (AT/RT) and primitive neuroectodermal tumors (PNET). [1] Several newer morphological variants of CNS embryonal tumors have been reported during the past one decade including embryonal tumor with abundant neuropil and true rosettes/embryonal tumor with multilayered rosettes (ETANTR/ETMR). [2],[3] This variant has not yet been included as a separate entity in the WHO classification of CNS tumors. [1] We report two cases of ETMR here as there are no earlier published reports of this unique entity from the Indian subcontinent.


 » Case Reports Top


Case 1

A two-year-old male child presented with one episode of low-grade fever and seizure, multiple episodes of vomiting and headache and weakness of the right side of the body since 10 days. Magnetic resonance imaging (MRI) scan demonstrated a 6.4 × 6.8 × 5.9 cm heterogeneous mass lesion with solid and cystic components, mass effect and mild midline shift in the left fronto-parietal region. The solid component was hypointense on T2-weighted (T2W) images [Figure 1]a, isointense on T1-weighted (T1W) images with minimal contrast enhancement [Figure 1]b and showed restricted diffusion. The cystic component was hyperintense on T2W images [Figure 1]a, hypointense on Fluid Attenuation Inversion Recovery FLAIR and T1W images without any contrast enhancement. The imaging features were suggestive of a PNET. He underwent left temporo-parietal craniotomy with gross total resection. The tumor was seen adherent to the dura and had a poor plane of cleavage from the adjacent brain parenchyma. The superficial component of the tumor was yellowish, soft, necrotic and non-vascular while the deeper component was reddish brown, soft, and very vascular. He had an uncomplicated postoperative course. He was sent for adjuvant chemotherapy and has been under follow-up for the past six months with no evidence of recurrence.
Figure 1: Case1-(a) T2W sagittal image showing a heterogeneous mass lesion in the left fronto-parietal region with solid and cystic components. (b) Post-contrast axial image shows minimal heterogeneous enhancement of the lesion. Case 2- (c) T2W axial image showing a heterogeneous mass lesion in the right parieto-occipital region with solid and cystic components (d) Post-contrast axial image shows heterogeneous irregular enhancement of the lesion

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Case 2

A three-year-old female child was admitted with history of multiple episodes of non-projectile vomiting, headache, one episode of complex partial seizure, difficulty in walking and restricted lateral movements of the right eye of seven days duration. Neurological examination showed leftlateral rectus palsy. MRI scan showed a 6.2 × 6.2 × 5.5 cm solid-cystic mass lesion in the right parieto-occipital region. The solid component was hypointense on T2W images and showed restricted diffusion. There were few irregular hyperintense cystic areas within the lesion [Figure 1]c. On T1W images, the solid component was isointense with irregular, heterogeneous contrast enhancement [Figure 1]d. The cystic component was mildly hypointense on T1W images and hyperintense in T2W images. There was mild mass effect on the right lateral ventricle without significant perilesional edema. The imaging features were suggestive of a PNET. She underwent right temporo-parietal craniotomy with gross total resection. On opening the dura, a large, soft, friable, moderately vascular grey-white tumor was seen in the right parietal region with a poor plane of cleavage from the adjacent neural parenchyma. Postoperative MRI scan showed no residual tumor. She received craniospinal irradiation with concurrent chemotherapy with six cycles of vincristine/cisplatins/lomustine. One year after the initial surgery she presented with two episodes of left-sided focal seizures. A repeat MRI done showed a recurrence of the mass lesion in the right temporo-parietal region. A re-exploration with gross total excision of the tumor was done. She was again sent for adjuvant chemotherapy. One year after the second surgery she had a second recurrence and was advised surgery. However, she was lost to follow-up since this last visit.

Histopathological sections in both patients showed a neoplasm composed of undifferentiated small cells in sheets and as multilayered perivascular rosettes [Figure 2]a, d, [Figure 3]a, e, numerous multilayered ependymoblastic rosettes [Figure 2]b, c, [Figure 3]b, c and clusters of monomorphic neurocytoma-like cells with clear cytoplasm and vesicular nuclei [Figure 2]d, e, [Figure 3]d, e in an abundant fibrillary/neuropil stroma. The rosettes showed well-formed central oval or slit-like lumina in the absence of an outer membrane. These lumina were either empty or filled with periodic acid schiff (PAS)-negative eosinophilic material. Brisk mitotic activity was seen in the undifferentiated zone as well as in the ependymoblastic rosettes [Figure 2]a, c. The first case showed foci with clusters of large ganglion cells [Figure 2]f, whereas the second case showed a few pleomorphic bizarre large cells [Figure 3]f. Immunohistochemisty was performed using the following panel of antibodies: synaptophysin (1:100), epithelial membrane antigen (EMA) (1:100), glial fibrillary acidic protein (GFAP) (1:100), vimentin (1:100) [Novocastra, Newcastle upon Tyne, UK] [Figure 4]. Relevant histopathological and immunohistochemical findings are highlighted in [Table 1] and [Table 2]. Based on the above morphology a diagnosis of ETMR with dominant neuronal differentiation showing abundant neuropil stroma (Case 1) and ETMR with dominant glial differentiation (Case 2) was given.
Figure 2: Case 1- (a) PhotomicroGraph of hypercellular zone with undifferentiated small cells in sheets. (b) Ependymoblastic rosettes in a paucicellular neuropil stroma. (c) Multilayered ependymoblastic rosettes with a mitotic Figure and central round lumen. (d) Multilayered perivascular rosettes with undifferentiated cells and surrounding neurocytoma-like cells with clear cytoplasm in a neuropil stroma. (e) Undifferentiated cells and clear cells in a neuropil background. (f) Neoplastic large ganglion cells surrounded by small hyperchromatic cells (H and E: a,b ×200: c,d,f ×400: e ×100)

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Figure 3: Case 2- (a) PhotomicroGraph showing undifferentiated small cells arranged around vessels. (b) Paucicellular zones showing numerous ependymoblastic rosettes scattered within abundant fibrillary stroma. (c) Multilayered rosettes with central oval lumen seen in fibrillary stroma. (d) Clear cells in abundant fibrillary stroma. (e) Clear cells admixed with clusters of undifferentiated small cells. (f) Large, bizarre cells with hyperchromatic nuclei (H and E: b ×100: a,d ×200: c,e,f ×400)

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Figure 4: Case 1- a,b,c: Case 2-d,e,f.(a) Cells in ependymoblastic rosettes and (b) undifferentiated small cells showing strong cytoplasmic positivity for vimentin. (c) Intervening neuropil stroma positive for synaptophysin. (d) Ependymoblastic rosettes in Case 2 with strong vimentin positivity. (e) Rosettes were negative for GFAP and fibrillary stroma showed strong GFAP positivity. (f) (Avidin-Biotin Complex: a,c,f ×200: b,d,e ×400)

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Table 1: Salient histopathological features of the two cases of ETMR

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Table 2: Relevant immunohistochemical (IHC) findings of the two cases of ETMR

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 » Discussion Top


Eberhart et al., in 2000 had described a unique embryonal tumor in children which he coined as pediatric neuroblastic tumor containing abundant neuropil and ependymoblastic rosettes (PNTANTR). [2] This tumor showed a biphasic pattern with undifferentiated cells having small hyperchromatic nuclei, well-differentiated neuronal cells such as clear neurocytoma-like cells and large ganglion cells and clusters of multilayered rosettes (ependymoblastic and perivascular) distributed in an abundant paucicellular fibrillary neuropil background. Subsequently this tumor was designated as ETANTR. [2],[4] Since the initial description of this entity, approximately 75 cases with similar histology have been published in the literature. [5]

Ependymoblastoma (EBL), another malignant neoplasm categorized under CNS-PNET in the WHO classification shares some of the clinical and histomorphological features of ETANTR. [2],[6] EBL also occurs in the pediatric age group and is characterized by the presence of ependymoblastic rosettes as well as undifferentiated small cells. [1] Since its initial description by Bailey and Cushing it has been widely debated whether EBL should be regarded as a distinct entity. [7],[8] Judkins and Ellison considered the term 'EBL' as neither precise nor specific and suggested that EBL should be excluded from the classification of CNS tumors based on a retrospective study of 14 EBLs in which they found eight cases with the histopathological features of ETANTR. [6]

A unique chromosome band 19q13.42 containing a cluster of micro-RNA-coding genes was detected in both EBL and ETANTR by Pfister and Korshunov. [9],[10] This hallmark cytogenetic feature suggested that both these tumors are a single biological entity originating from a common precursor cell. Hence, Paulus and Kleihues proposed a more uniformly accepted terminology of embryonal tumor with multilayered rosettes (ETMR) for this entity. They also suggested that fluorescence in situ hybridization (FISH) analysis of Chromosome 19q13.42 can be used a novel molecular marker for the diagnosis of ETMR, particularly in those cases where the diagnosis becomes difficult by histomorphology alone. [3]

In spite of the characteristic histological features, cases of ETMR with composite morphology have been reported. They include ETMR with features of mesenchymal and epithelial differentiation, [4] medulloepitheliomatous differentiation [11] and dominant neurocytic differentiation. [12] Similarly, our case of ETMR had a dominant glial differentiation amidst the ependymoblastic rosettes. This may be attributed to metaplastic changes or divergent differentiation of tumor stem cells similar to that seen in other neuroepithelial tumors.

ETMR is said to have a more dismal prognosis compared to medulloblastoma and neuroblastoma. [2],[9],[12] However, cases with a long period of survival following surgery have been reported. [4] Our case of ETMR with dominant glial differentiation had a long survival period of two years following surgery. The significance of such morphological variations or any specific molecular markers that may play a role in the long-term survival of these cases is still not understood. With the advent of new molecular markers, it will be possible to provide newer insights into the biological behavior as well as for developing effective targeted therapies for ETMR in future.


 » Acknowledgment Top


The authors express their sincere gratitude to the Director of our institute for permitting to publish this article.

 
 » References Top

1.Louis D, Ohgaki H, Wiestler O, Cavenee W. WHO classification of tumours of the central nervous system. 4th ed. Lyon, France: IARC Press; 2007. p. 141-6.  Back to cited text no. 1
    
2.Eberhart CG, Brat DJ, Cohen KJ, Burger PC. Pediatric neuroblastic brain tumors containing abundant neuropil and true rosettes. Pediatr Dev Pathol 2000;3:346-52.  Back to cited text no. 2
    
3.Paulus W, Kleihues P. Genetic profiling of CNS tumors extends histological classification. Acta Neuropathol 2010;120:269-70.  Back to cited text no. 3
    
4.Gessi M, Giangaspero F, Lauriola L, Gardiman M, Scheithauer BW, Halliday W, et al. Embryonal tumors with abundant neuropil and true rosettes: A distinctive CNS primitive neuroectodermal tumor. Am J Surg Pathol 2009;33:211-7.  Back to cited text no. 4
    
5.Wang Y, Chu SG, Xiong J, Cheng HX, Chen H, Yao XH. Embryonal tumor with abundant neuropil and true rosettes (ETANTR) with a focal amplification at chromosome 19q13.42 locus: Further evidence of two new instances in China. Neuropathology 2011;31:639-47.  Back to cited text no. 5
    
6.Judkins A, Ellison D. Ependymoblastoma: Dear, damned, distracting diagnosis, farewell!*. Brain Pathol 2010;20:133-9.  Back to cited text no. 6
    
7.Bailey P, Cushing H. A classification of the tumors of the glioma group on a histogenetic basis with a correlated study of prognosis. Philadelphia; J.B. Lippincott Co; 1926.  Back to cited text no. 7
    
8.Mork SJ, Rubinstein LJ. Ependymoblastoma: A reappraisal of a rare embryonal tumor. Cancer 1985;55:1536-42.  Back to cited text no. 8
    
9.Pfister SM, Remke M, Castoldi M, Bai AH, Muckenthaler MU, Kulozik A, et al. Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes. Acta Neuropathol 2009;117:457-64.  Back to cited text no. 9
    
10.Korshunov A, Remke M, Gessi M, Ryzhova M, Hielscher T, Witt H, et al. Focal genomic amplification at 19q13.42 comprises a powerful diagnostic marker for embryonal tumors with ependymoblastic rosettes. Acta Neuropathol 2010;120:253-60.  Back to cited text no. 10
    
11.Buccoliero AM, Castiglione F, Degl'innocenti DR, Franchi A, Paglierani M, Sanzo M, et al. Embryonal tumor with abundant neuropil and true rosettes: morphological, immunohistochemical, ultrastructural and molecular study of a case showing features of medulloepithelioma and areas of mesenchymal and epithelial differentiation. Neuropathology 2010;30:84-91.  Back to cited text no. 11
    
12.Dunham C, Sugo E, Tobias V, Wills E, Perry A. Embryonal tumor with abundant neuropil and true rosettes (ETANTR): Report of a case with prominent neurocytic differentiation. J Neurooncol 2007; 84:91-8.  Back to cited text no. 12
    


    Figures

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

  [Table 1], [Table 2]

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