Ependymoblastoma in an adult: a diagnostic challenge on cytology

Abstract

Ependymoblastoma is a rare, highly malignant brain tumour considered by most to be a subtype of primitive neuroectodermal tumour manifesting in young children. The authors present an unusual case of ependymoblastoma occurring in an 18-year-old female, one of the oldest patients reported with this tumour. The crush smears were highly cellular comprising singly scattered small, round immature cells with fine granular chromatin. The paraffin sections showed a tumour composed of uniform, small-sized, primitive cells forming well defined multi-layered rosettes with prominent mitoses. The tumour cells exhibited diffuse Vimentin and focal glial fibrillary acidic protein reactivity. A few cells showed S-100 reactivity. The patient underwent radiotherapy following complete tumour debulking but, succumbed to the disease within 2 months of diagnosis.

Background

Ependymoblastoma is considered to be a malignant glioma with ependymal differentiation. This rare tumour occurs in very early life and shows rapid growth and diffuse infiltration through the leptomeningeal space.¹ The tumour is presumed to arise from periventricular neuro-epithelial precursor cells.² The revised version of WHO of central nervous system (CNS) tumours places ependymoblastoma in a group of primitive neuroectodermal tumours (PNET) with the capacity to differentiate into ependymal cells. Within this classification, ependymoblastoma has clear histological characteristics which allow its differentiation from medulloblastoma and other PNETs.³ Although there have been sporadic case reports of this rare tumour occurring in older age, description of cytological features has been extremely scarce. We conclude that rare cases of ependymoblastoma may be encountered in adults. Further, the cytological features are sufficient to suggest a diagnosis of embryonal tumour yet, not specific for a diagnosis of ependymoblastoma.

Case presentation

An 18-year-old girl sought medical help for gradually worsening left-sided headache and diplopia over period of 3 months associated with two episodes of generalised convulsions. There was no history of vomiting, other focal neurological deficit or trauma. On neurological examination, patient was alert, well oriented with no sensori-motor deficit. Ophthalmic examination revealed medial deviation of left eye along with papilloedema in the left eye fields.

Contrast enhancing CT scan disclosed a large, circumscribed, heterogenous space occupying lesion in the left temporo-frontal region with minimal peri-lesional oedema. Focal cystic component and calcified dots were noted and the lesion showed heterogenous contrast enhancement. There was midline shift to right side with partial obliteration of the basal cisterns (figure 1). Subsequent MRI localised the 5×7×4.5 cm lesion to left frontal lobe, with extension into the adjacent temporal and parietal lobes. The lesion was predominantly hyperintense on T2 WIs, T2 FLAIR and hypointense on TI WIs. Based on CT and MRI findings, a diagnosis of left-sided anaplastic fronto-temporal glioma was suggested. The patient underwent open craniotomy and total tumour debulking was done.

Figure 1.

CT scan showing large heterogenous space occupying lesion in temporo-frontal area with cystic component and few calcified dots. Medial deviation to right is also seen.

The specimen was received in two containers; a small part of tissue in normal saline for crush preparation and the rest in 10% buffered formalin for histopathological examination consisting of few irregular grey white soft tissue pieces altogether measuring 2×1 cm.

The H&E stained crush smears were highly cellular comprising dispersed population of uniform round to oval cells. The cells were primitive looking with high nucleocytoplasmic ratio, ill-defined cytoplasm and round nuclei with fine granular chromatin. Nuclear overlapping, moulding and atypical mitotic figures were seen (figure 2). A cytological diagnosis of PNET was suggested. The histopathological sections revealed tumour of high cellularity composed of small sized cells arranged in diffuse sheets punctuated by true rosettes and canals characterised by radial arrangement of cells around empty lumen with conspicuous juxtaluminal mitoses. The tumour cells were poorly differentiated with granular chromatin (figures 3 and 4). Immunohistochemistry revealed diffuse positivity for Vimentin and focal glial fibrillary acidic protein (GFAP) reactivity. Perinuclear S-100 protein reactivity was seen in few cells. Final diagnosis of ependymoblastoma was thus rendered and patient underwent postoperative radiotherapy.

Figure 2.

Crush cytology smears showing highly cellular tumour composed of monotonous population of singly lying primitive cells with high nucleocytoplasmic ratio and fine granular chromatin. A mitotic figure is also seen (arrow) (HE ×400).

Figure 3.

Histopathological section showing tumour composed of ependymoblastic rosettes and canals (HE ×100).

Figure 4.

High power view showing ependymoblastic rosettes composed of concentric arrangement of immature small round tumour cells around empty lumina with conspicuous juxtaluminal mitoses (arrow) (HE ×400).

Outcome and follow-up

The patient underwent postoperative radiotherapy following tumour debulking but, succumbed to the disease within 2 months of diagnosis.

Discussion

The term ‘ependymoblastoma’ was used originally by Bailey and Cushing,⁴ who proposed that the tumours arising from ependyma should be divided into two subgroups namely, ependymoma and ependymoblastoma. However, subsequently this subclassification was discarded by its original proponents as both these entities were devoid of mitotic activity and shared blepharoplasts characteristic of adult ependymal elements.^{1 5} Meanwhile, the term ‘ependymoblastoma’ was retained⁵ and redefined by Rubinstein as a special type of embryonal CNS neoplasm occurring in young individuals wherein the cytological features of a primitive highly cellular neuroectodermal tumour are associated with the presence of numerous true or ependymal rosettes.^{1 6} The recent revision of the WHO Classification of CNS tumours places ependymoblastoma in a group of primitive neuroectodermal tumours with the capacity to differentiate along one or more cell lines, in this case with ependymal differentiation.³

Clinically, these tumours display extremely aggressive course with tendency toward local invasion, recurrence and infiltration of leptomeninges and correspond to WHO grade IV ³ with a median survival of 1 year.² Ependymoblastoma arise in early life as do other PNETs, with a mean age at presentation of 4.7 years.¹ However, there have been reports of these tumours occurring in older age group. Dorhman et al⁷ and Shu-Hang et al² have reported ependymoblastoma occurring in patients aged 18 years and 14 years respectively while, Mork and Rubinstein⁵ reported two other cases occurring in 16 and 36 year old individuals. A case of disseminated primary leptomeningeal ependymoblastoma was reported by Wada et al¹ in a 17-year-old girl. Thus, the present case falls in the same category of rare cases of ependymoblastoma presenting in older age group.

These neoplasms are usually large and well circumscribed with younger individuals tending to attain a larger tumour size. Focal necrosis, haemorrhage and cystic change may be seen.⁵ Radiologically, the presence of a large clearly demarcated supratentorial mass with remarkably minimal oedema and heterogeneous contrast enhancement suggests the possibility of this lesion.^{2 8} Ependymoblastomas generally relate to the ventricles, although they do occur at other sites.³ Mork and Rubinstein,⁵ in a review of 12 ependymoblastoma cases found only four tumours related to the ventricular lining while, seven others were clearly separated from the ventricular wall. These lesions have presumably arisen from ectopic ependymal cell nests that are frequently found in the periventricular white matter.⁵ In the present case, the temporo-frontal location of the tumour without any relation to the ventricles represents a similar histogenesis.

The histological diagnostic feature of ependymoblastoma is its dense cellularity with numerous distinctive multi-layered rosettes formed by concentric arrangement of cellular rings around small round lumina.^{3 5 9} The tumour cells are poorly differentiated, oval to spindle shaped with ill-defined cytoplasm and wispy polar processes.⁵ Features which identify these tumours as embryonal are the small cell size, uniform appearance and round or ovoid nuclei showing frequent mitoses.⁹ The structure of ependymoblastic rosette corresponds to the later phase of neural tube development characterised by multilayering of cells and abundant mitotic activity in juxtaluminal position.^{5 9}

Though an established entity, there is extreme paucity of literature regarding the cytopathological aspects of ependymoblastoma. The aspirates in ependymoblastoma are highly cellular and though rosettes may be seen, they are generally rare.¹⁰ The cytological features in the present cases tallied with those of Kaoru et al¹¹ who reported a case of ependymoblastoma of the nasal cavity wherein the imprint smears revealed small round uniform cells with scant cytoplasm and fine granular nuclei. However, unlike their case, in the present case rosettes were not appreciated on cytology although they were conspicuous in histological sections.

Immunohistochemical profile revealed S-100 and Vimentin positivity in all cases reviewed by Cruz-Sanchez et al.^{9 12} The authors observed that, in contrast to medulloblastomas, vimentin reactivity in ependymoblastomas was present in most cells throughout the tumour and its intensity was stronger, indicating a later stage of maturation in the latter group. GFAP was found to be absent or only sparsely positive in few tumour cells.¹² However, glial or neural differentiation using immunohistochemical markers was not detected in the case of primary leptomeningeal ependymoblastoma reported by Wada et al.¹ In the present case, diffuse and intense tumour cell positivity for vimentin was seen with few cells showing GFAP reactivity and only sparse number of cells demonstrated neural differentiation in the form of perinuclear S-100 positivity.

Ependymoblastomas must be distinguished from anaplastic ependymomas. Ependymoblastomas do not have well developed pseudorosettes and seldom have the degree of cytoplasmic or nuclear pleomorphism characteristic of the anaplastic ependymomas. Necrosis may be present in both tumour types although, geographic and psuedopalisading patterns of necrosis are only found in anaplastic ependyomas.¹³ Medulloepitheliomas may contain ependymoblastoma type rosettes but they can be distinguished by their diagnostic neuroepithelium characterised by an outer basement membrane arranged in tubular, canalicular and papillary patterns. Medulloblastoma are differentiated by their cerebellar location and characteristic Homer-Wright rosettes which lack a central lumen.³

Recently, Judkins and Ellison¹⁴ have challenged the existence of this entity. They reviewed 14 embryonal brain tumours and found ependymoblastic rosettes as a key diagnostic feature in 79% tumours while remaining showed similar rosettes in a setting of other typical embryonal tumours. The authors believe that ependymoblastoma as a diagnosis is neither precise nor specific and it is time for this diagnosis to depart from the lexicon of neuropathology. Although retained in latest WHO Classification, such experience may pave way for future modifications in diagnostic categorisation of these tumours.

Learning points.

• ▶Though predominantly a tumour of young children, rare ependymoblastoma cases may occur in adults.
• ▶The cytology of ependymoblastoma is diagnostically challenging since it recapitulates other embryonal tumours.
• ▶Definite distinction from other embryonal tumours is achieved only on histopathology by the presence of characteristic multi-layered rosettes.