Keywords
primitive neuroectodermal tumors - ependymoblastoma - neuroblastoma
Palavras-chave
tumores neuroectodérmicos primitivos - ependimoblastoma - neuroblastoma
Introduction
According to the World Health Organization (WHO) classification, there are three types
of primitive embryonal tumors of the central nervous system: medulloblastoma, atypical
teratoid/rhabdoid tumor and primitive neuroectodermal tumor (PNET). The latter has
five subtypes: primitive neuroectodermal tumor not otherwise specified (PNET-NOS),
neuroblastoma, ependymoblastoma, medulloepithelioma and ganglioneuroblastoma.[1]
[2]
The embryonal tumor with abundant neuropil and true rosettes (ETANTR) is an extremely
rare variant of the PNET, with characteristics in common with both the neuroblastoma
and the ependymoblastoma. There are ∼ 80 published cases since its first description
in the literature, in 2000, by Eberhart et al.[2]
[3]
The ETANTR occurs in very young patients, especially in children under 6 years of
age, with a slight predominance in females, and it is found in the cerebellum, brainstem,
pineal gland and especially the in the cerebral cortex, with greater predilection
for the frontal and parietal lobes.[2]
[4]
[5] We present herein the first report in Brazil, published in indexed literature, of
an ETANTR case involving a young child.
Case Report
A 3-year-old male patient has reported headache with progressive intensity, disorientation
and partial motor seizures during 20 days of hospitalization. About 18 hours after
the patient's admission to the emergency neurosurgery service of a hospital in Brasília,
Brazil, the symptoms evolved with a sudden decrease in the level of consciousness,
anisocoria and right decerebration.
A brain computed tomography (CT) scan showed the presence of a heterogeneous lesion,
with cystic areas and inner calcification, located in the right frontal lobe and subfalcine
herniation of ∼ 12 mm to the left ([Fig. 1]).
Fig. 1 Skull computed tomography without contrast shows heterogeneous right frontal lesion
and subfalcine herniation. Source: Radiology Department of the Hospital de Base do
Distrito Federal – Brasília - Brazil.
The patient underwent emergency decompressive craniotomy with complete excision of
the tumor and the overlying dura. Macroscopically, it presented as an injury that
was fibroelastic, slightly hemorrhagic, had well-defined borders in most of its length,
invading the dura but not involving the skull. A duraplasty was performed with autologous
pericranium.
The histopathology examination showed a primitive supratentorial neuroectodermal tumor
with areas of ependymoblastoma and areas of abundant neuropil, presence of necrosis,
atypia, pleomorphism cells as well as mitoses (grade IV as per the WHO classification
of tumors of the central nervous system) ([Fig. 2]). The immunohistochemistry showed positivity for vimentin (VIM) and negativity for
pancytokeratin (PANCK), glial fibrillary acidic protein (GFAP), epithelial membrane
antigen (EMA), S-100 protein, neuron-specific enolase (NSE) and p-53 protein. The
Ki-67 protein was present in 30–40% of the cells ([Fig. 3] and [Table 1]). Lesions with these features have been considered as ETANTRs.
Table 1
Results of immunohistochemical markers
|
Markers
|
Results
|
|
GFAP
|
negative
|
|
EMA
|
negative
|
|
S-100
|
negative
|
|
VIM
|
positive
|
|
PANCK
|
negative
|
|
MELAN-A
|
negative
|
|
CEA
|
negative
|
|
Ki-67
|
30–40%
|
Abbreviations: CEA, carcinoembryonic antigen; EMA, epithelial membrane antigen; GFAP,
glial fibrillary acidic protein; Ki-67, Ki-67 protein; Melan-A, melanoma antigen;
PANCK, pancytokeratin; S-100, S-100 protein; VIM, vimentin.
Source: Service of Pathology of Hospital de Base do Distrito Federal, Brasília, Brazil.
Fig. 2 Histopathology, hematoxylin-eosin coloration. (A) Embryonic tumor with neuropilic
areas and ependymoblastic rosettes, (B) Perivascular rosettes, (C) Undifferentiated
neuroepithelial areas and (D) Pseudo-rosette with accentuated pleomorphism. Source:
Pathology Department of the Hospital de Base do Distrito Federal – Brasília - Brazil.
Fig. 3 Immunohistochemistry. (A) positive VIMENTINE marker and (B) Ki-67 positive in 30–40%.
Source: Pathology Department of the Hospital de Base do Distrito Federal – Brasília
- Brazil.
The patient remained hospitalized for 2 days in the intensive care unit (ICU), intubated,
sedated and on mechanical ventilation. On the 10th day postoperatively, he was discharged
from the hospital, conscious and oriented, with no motor or sensory deficit and without
seizures.
The patient has been followed-up at an outpatient chemotherapy setting and, currently,
there are no complaints.
Discussion
In this report, the patient presented with severe and rapidly progressive clinical
signs, which is consistent with the literature. Headache, focal signs, seizures, increased
head circumference and psychomotor developmental delay are the most frequent symptoms
of ETANTR.[6] Imaging exams show heterogeneous injuries unenhanced and contrast-media enhanced.
The ETANTR may show calcifications or cysts, as seen in our patient.[5]
[6] Its main differential diagnoses are desmoplastic infantile ganglioma, supratentorial
ependymomas and PNETs.[2]
Histologically, it displays the characteristics of both an ependymoblastoma and a
neuroblastoma, showing areas of neuroepithelium fibrillar with ependymoblastic rosettes
interposed and undifferentiated neuroepithelial cells. The ETANTR is distinguishable
from other embryonal tumors due to the abundance of neuroepithelium, and it often
has more ependymoblastic rosettes than the ependymoblastomas themselves.[2]
The immunohistochemistry normally shows positivity for synaptophysin in the neuroepithelial
cells, microtubule associated protein 2 (MAP2) in the tumor cells and for VIM, p53
protein, Nestin and β-catenin in the ependymoblastic rosettes. There was no evidence
of EMA or cluster of differentiation 99 (CD99) in any of the components.[4]
[7]
Genetic studies have demonstrated the presence of polysomy of chromosome 2, and the
amplification of chromosome 19q13.42. This last change, in special, can also be found
in ependymoblastomas and medulloepytheliomas.[2]
[3]
[8]
[9]
In most of the case reports, extensive surgical resections of the lesions were performed,
followed by a high dose of chemotherapy and, when possible, craniospinal radiotherapy.
Similarly to PNETs, the ETANTRs seem to be less sensitive to chemotherapy.[1]
[2]
The ETANTR is an extremely aggressive tumor, with a mean survival between 9 and 48
months. Better prognosis is usually found in older children, perhaps because they
can make use of adjuvant radiotherapy.[2]
[5]
