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 examination 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 resection of the tumor.

Figure 1.

Figure 2.

PATHOLOGIC FINDINGS

Gross examination of the tumor showed white‐tan soft friable tissue. Microscopically, the tumor consisted of highly cellular clusters of small to medium‐sized cells with hyperchromatic round 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 (ependymoblastomatous 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 material. 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). Immunohistochemical 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 (10, 11). Neurofilament 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 etoposide (VP16). Unfortunately, the patient developed recurrent disease 6 months after resection and chemotherapy.

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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 ganglioneuroblastoma, 4) medulloepithelioma, and 5) ependymoblastoma. (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 “Embryonal 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 neuroblastoma 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 abundant neuropil and true rosettes. The tumor involved the frontoparietal 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 presentation. 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.

In summary ETANTR is a very rare, highly aggressive CNS neoplasm and we are reporting here an additional case to the previously reported thirteen cases, which also represents the second case occurring in the cerebellum.

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 cerebellum to the roof of the fourth ventricle. The tumor was diagnosed 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.