doi:10.1111/j.1750-3639.2009.00279.
x
C O M N O V. 2 0 0 8 C A S E 2
POSTERIOR FOSSA TUMOR IN A 2 YEAR-OLD GIRL
CLINICAL HISTORY
A 2-year-old girl was admitted to the department of neurosciences,
King Faisal Specialist Hospital and Research Center, Riyadh,
Saudi Arabia, with three weeks history of deterioration of walking,
then became unable to walk and later she developed a projectile
vomiting mostly in early morning. There was no history of seizures
or loss of consciousness. At admission her neurological examina-
tion revealed bilateral papilledema, nystagmus and truncal ataxia
with intention tremor. Magnetic Resonance Images (MRI) of the
brain showed a 3 ¥ 4 cm posterior fossa enhancing mass extending
from the base of the cerebellum to the roof of the fourth ventricle
without calcification (fig. 1, sagittal T-1 weighted with contrast)
and (figure 2: axial T2-weighted with contrast). Then, the patient
underwent midline suboccipital craniotomy with a near total resec-
tion of the tumor.
PATHOLOGIC FINDINGS
Gross examination of the tumor showed white-tan soft friable
tissue. Microscopically, the tumor consisted of highly cellular clus-
ters of small to medium-sized cells with hyperchromatic round
Figure 1.
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to oval nuclei and indistinct cell borders (figure 3) admixed with
areas showing fine fibrillary, paucicellular, neuropil-like matrix
(figure 4). Also noted were areas containing true rosettes (ependy-
moblastomatous type) with well-formed central lumina (figure 5).
These rosettes consisted of multilayered cells with hyperchromatic
nuclei, numerous mitotic figures and apoptotic bodies (figure 6).
The lumina of some rosettes contained granular eosinophilic mate-
rial. Periodic Acid Schiff (PAS) special stain was positive along the
luminal border of the true rosettes and highlighted some of the
granular material within the lumina (figure 7). Immunohistochemi-
cal studies were characterized by positivity for synaptophysin
(figure 8) and CD56 (figure 9) in the neuroblastic tumor cells and
neuropil-like areas. Glial fibrillary acidic protein (GFAP) was only
positive in scattered cells in these areas (figure 10 & 11). Neu-
rofilament protein was negative. The true ependymoblastomatous
rosettes were negative for CD56, GFAP and synaptophysin but
they strongly expressed vimentin (figure 12). The Ki-67 was much
higher in the ependymoblastomatous rosettes (over 90%) than in
the neuroblastic areas (approximately 15%), as seen in (figure 13).
The patient was then treated with chemotherapy which included
courses of cyclophosphamide and vincristine, cisplatin and etopo-
side (VP16). Unfortunately, the patient developed recurrent disease
6 months after resection and chemotherapy.
Figure 2.
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Figure 3.

Figure 4. Figure 5.

344 Brain Pathology 19 (2009) 343–346

© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
 Correspondence

Figure 6. Figure 7.

Figure 8. Figure 9.

Figure 10. Figure 11.

Figure 12. Figure 13.

Brain Pathology 19 (2009) 343–346 345

© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
Correspondence
DIAGNOSIS
Embryonal Tumor with Abundant Neuropil and True Rosettes
(ETANTR).
DISCUSSION
The 2007 World Health Organization (WHO) classification of
central nervous system (CNS) tumors classifies the embryonal
tumors into three categories: 1) Medulloblastoma, 2) Atypical
teratoid/rhabdoid tumor, and 3) CNS primitive neuroectodermal
tumor (PNET). The latter category (PNET) includes five sub-
categories: 1) CNS PNET; 2) CNS neuroblastoma, 3) CNS gan-
glioneuroblastoma, 4) medulloepithelioma, and 5) ependymo-
blastoma. (7). In the “CNS PNET” section of the 2007 WHO
classification of tumors of the CNS, there is a short paragraph,
describing an extremely aggressive type of tumor called “Embryo-
nal tumor with abundant neuropil and true rosettes” (ETANTR),
suggesting that this tumor might eventually be considered as a
separate entity (7).
Embryonal tumors with abundant neuropil and true rosettes
were first reported as neuroblastic tumors with abundant neuropil
and true rosettes in 2000 by Eberhart et al (3), who described nine
cases. In 2006, three additional cases were been reported, one case
by Spina et al (6) and two cases by Fuller et al (4). Recently, in
2007, an additional case was reported by Dunham et al (2). These
cases are summarized in a table on-line (see: http://path.upmc.edu/
divisions/neuropath/bpath/cases/case175/dx.html
All ETANTR cases reported so far have been in children aged 4
years old or less. This tumor combines the features of a neuroblas-
toma and an ependymoblastoma, by showing fine fibrillary
neuropil-like areas admixed with cellular regions and
ependymoblastoma-like rosettes. Nevertheless, Homer Wright
rosettes are absent or rarely identified. Eberhart et al (3) reported
nine cases of tumors in children ages 1–3 years containing abun-
dant neuropil and true rosettes. The tumor involved the frontopari-
etal region in six cases, the frontal lobe in one case, the cerebellum
in one case and the tectal plate in the last case. Two additional cases
were described in an addendum, one involved the cerebellum and
the other in the frontal lobe. These were positive for synaptophysin
and neurofilament protein and only one case showed focal GFAP
positivity (3). Most of the patients died 5–14 months after presen-
tation. Spina et al (6) reported a 4-year old boy who presented with
an infiltrating ETANTR of the pons and midbrain. Histologically,
the tumor was similar to that described by Eberhart et al (3).The
tumor cells were positive for synaptophysin and negative for GFAP.
Their patient was alive 34 months after surgery with no evidence of
disease. Fuller et al (4) reported two cases in 4-year-old children (a
midpontine tumor and a large cerebral lesion). The first case
showed polysomy of chromosomes 2, 8, 17, and 22. The second
case showed isochromosome 17q which is molecular alteration
typical of medulloblastomas. The midpontine tumor was stable at
19 months but in the other case the patient died 6 months after
initial examination. Recently, Dunham et al (2) reported a case
occurring in a 2-year-old boy as a large left temporoparietal mass.
The tumor exhibited extensive neurocytic differentiation. Their
patient developed recurrence approximately after one year. Similar
cases have been previously described as ependymoblastoma and
neuroblastoma (1, 5).
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© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
In summary ETANTR is a very rare, highly aggressive CNS
neoplasm and we are reporting here an additional case to the previ-
ously reported thirteen cases, which also represents the second case
occurring in the cerebellum.
REFERENCES
1. Cenacchi G, Giangaspero F (2004) Emerging tumor entities and
variants of CNS neoplasms. J Neuropathol Exp Neurol 63(3):
185–192.
2. Dunham C, Sugo E, Tobias V, Wills E, Perry A (2007) Embryonal
tumor with abundant neuropil and true rosettes (ETANTR): report of a
case with prominent neurocytic differentiation. Journal of
Neuro-Oncology. 84(1):91–98.
3. Eberhart CG, Brat DJ, Cohen KJ, Burger PC (2000) Pediatric
neuroblastic tumors containing abundant neuropil and true rosettes.
Pediatr Dev Pathol. 3:346–352.
4. Fuller C, Fouladi M, Gajjar A, Dalton J, Sanford RA, Helton KJ (2006)
Chromosome 17 abnormalities in pediatric neuroblastic tumor with
abundant neuropil and true rosettes. Am J Clin Pathol 126:277–283.
5. Queiroz LS, de Faria JL, Cruz JN (1975) An ependymoblastoma of the
pons. J Pathol 115:207–212.
6. Spina ML, Pizzolitto S, Skrap M, Nocerino A, Russo G, Di Cataldo A,
Perilongo G (2006) Embryonal tumor with abundant neuropil and true
rosettes. A new entity or only variations of a parent neoplasms
(PNETs)? This is the dilemma. Journal of Neuro-Oncology
78:317–320.
7. WHO Classification of Tumors of the Central Nervous System (2007)
4th ed. IARC Press; Lyon, France: p 8–9.
Contributors:
Turki Omar Al-Hussain, MBBS, Mohammad Anas Dababo, MD
Department of Pathology and Laboratory Medicine
King Faisal Specialist Hospital and Research Center
Riyadh, 11211, Saudi Arabia
ABSTRACT
We report a case of a 2 year-old girl who presented with three
weeks history of deterioration of walking, then became unable to
walk and later she developed a projectile vomiting. Neurological
examination revealed bilateral papilledema, nystagmus, and
truncal ataxia with intention tremor. Radiological studies showed
an enhancing mass in the posterior fossa extending from the cer-
ebellum to the roof of the fourth ventricle. The tumor was diag-
nosed as an embryonal tumor with abundant neuropil and true
rosettes (ETANTR). The tumor cells in the neuroblastic component
were diffusely positive for synaptophysin and CD56, with scattered
positive cells for glial fibrillary acidic protein. The true rosettes
were only positive for vimentin. Ki67 showed high index (over
90%) in the true rosettes, while the neuroblastic areas were up
to 15%. Our patient developed recurrent disease 6 months after
resection and chemotherapy. ETANTR is a very rare aggressive
embryonal CNS tumor that combines features of neuroblastoma
and ependymoblastoma. We review the thirteen cases reported in
the literatures. This case represents the second report of an
ETANTR arising in the cerebellum.
Brain Pathology 19 (2009) 343–346