Rare Brain Tumor in a Neonate.

Neonatal brain tumor is rare and its outcome is generally poor. We reported a 17-day-old neonate presented as enlarged head girth. The pathological finding showed an embryonal tumor with multilayered rosettes.

Introduction

Brain tumors presented during neonatal period are rare that represent only 0.5–1.9% of all pediatric central neural system tumors [1]. Clinical presentation in the neonatal period, as the period of first 4 weeks after delivery, is not specific and the focal neurologic sign is subtle.

The availability of noninvasive imaging such as Trans-cranial Doppler ultrasonography, computer tomography (CT), magnetic resonance imaging (MRI) during the fetal and neonatal periods makes earlier diagnosis of these tumors possible. Transcranial Doppler ultrasonography may be the first modality to evaluate neonates clinically presenting with increasing head circumference, bulging fontanelle, lethargy or seizure.

Embryonal tumor with multilayered rosettes (ETMR), belongs to a new classification of embryonal tumors of the central nervous system according to the World Health Organization (WHO).

We present a case of ETMR and describe the clinical, pathological, and cranial ultrasonographic features of this rare tumor.

Case report

A 17-day-old male neonate presented with rapidly increased head girth. Head circumference was 39.5 cm (birth head circumference was 36 cm). He was born as a full-term to primigravida mother by lower segment cesar-ean section with Apgar scores were 9 at 1 min and 10 at 5 min. Birth weight was 3.48 kg. Maternal history and prenatal examination including chromosomal study of cultured amniocytes were normal. Prenatal sonographies were unremarkable until 37 weeks of gestational age. Physical examination revealed frontal bossing with bulging anterior fontanel.

Transcranial Doppler ultrasonography (PA6-8-D transducer,4–10 MHz, GE Voluson ultrasound machines) showed severe lateral ventricle dilatation, third ventricle dilatation, heteroechogenicity density over whole posterior fossa with displaced 4th ventricle and visible aqueduct (Fig. 1). The lateral ventricular ratio, between lateral ventricular width and hemispheric width [2], was 62.6% of left ventricle and 56.9% of right ventricle. The Doppler color-flow imaging revealed high resistance index = 0.85 and pulsatility index = 1.70 of anterior cerebral artery. Obstructive hydrocephalus and a suspected posterior fossa space occupying lesion were impressed. MRI confirmed a 4.5 × 4.9 × 5.7 cm3 tumor in cerebellar vermis with lateral and anterior extension as well as inferior extension to the foramen magnum. Compression on pons, medulla and 4th ventricle and evidence of obstructive hydrocephalus were seen (Fig. 2).

Figure 1

Sonographic image (a) in coronal view demonstrates with bilateral lateral ventricle and third ventricle dilatation. (b) Sagittal midline view shows hydrocephalus with 3rd ventricle dilatation, visible aqueduct (arrow), displaced 4th ventricle, unclear margin of vermis and cistern magna that indicated obstruction of lower CSF pathway. Space-occupying lesion (arrowhead) with heteroechogenicity in vermis is suspected.

Figure 2

(a)Sagittal T2WI MR scan demonstrates a huge tumor (arrow) with central cysts in the midline of the posterior cranial fossa appearing as heterogeneous high signal intensity about 4.5 × 4.9 × 5.7 cm3 in size and localized predominantly in the cerebellar vermis and hemispheres and toward inferior extension to the foramen magnum. The tumor leads to compression on pons, medulla and 4th ventricle and dilatation of aqueduct, 3rd ventricle and lateral ventricles. (b)Coronal T2 FLAIR shows tumor with heterogeneous high signal intensity. (c) Axial view in T1 FLAIR.

A suboccipital craniotomy for tumor resection was performed. Histological analysis of the resected specimen showed a hypercellular tumor which contains small cells with round to oval nuclei and scanty cytoplasm. Formation of multilayered rosettes, composed of pseudostratified tumor cells is seen. The primitive small cell areas are immunoreactive for vimentin, while the neuropil-like areas showing expression for synaptophysin. The Ki-67 labeling index is high in the cellular areas. The histopathologic features are compatible with an ETMR.

Discussion

The most common brain tumors diagnosed in the fetus/ neonate were teratomas (29%), followed by astrocytomas (18%). Primitive neuroectodermal tumor (PNET) makes up 13% of all fetal and neonatal brain tumor [34]. ETMR constitutes a distinct entity of the PNET family. ETMR was proposed in 2010 as a unifying entity by Paulus and Kleihues, including embryonal tumor with abundant neuropil and true rosettes (ETANTR), and ependymoblastoma [5]. This tumor presents a focal amplification of the C19MC region encoding a miRNA cluster of chromosome 19 (19q.13.42). In 2016 WHO classification of embryonal brain tumors [6], the term of PNETwas removed. In the presence of C19MC amplification, a tumor with histological features conforming to ETANTR/ ETMR should be diagnosed ETMR, C19MC-altered. In contrast, in the absence of C19MC amplification, ETMR, not otherwise specified should be diagnosed. Chromosome 19 expression studies were not available in our case.

ETMR are rare entities and underdiagnosed in the result of unclassified embryonal tumors and only a few cases reported in the past literature. They occur mostly in children aged less than 2 years old and their prognosis is poor. In the literature, the localization of the majority of ETMR is supratentorial with signs of increased intracranial pressure (66%) [7]. Our case showed a infratentorial tumor with hydrocephalus.

Most embryonal brain tumors in children grow rapidly and spread into other area of the brain. Depending on the type, size, and location of the tumor, obstruction of cere-brospinal fluid pathways can be seen. In the literature, infratentorial tumors were commonly found to have hy-drocephalus than supratentorial brain tumors [89].

Our case manifested as rapid growth infratentorial tumor leading to hydrocephalus in neonatal period. Neonatal brain tumors are rare and sometimes detected incidentally on routine prenatal or neonatal ultrasonogra-phy. These tumors may present with an increasing head circumference, bulging fontanel, vomiting, seizures, sunset eyes and also only with subtle symptoms such as irritability, poor feeding, failure to thrive.

Transcranial Doppler ultrasonography is a quick, convenient and also not expensive tool to evaluate cerebral structure via an open fontanel in neonates who presenting nonspecific symptoms. It can evaluate hydrocephalus in the neonatal patient and can be used to quantitate the progression of hydrocephalus, which can help for decision about neurosurgical intervention. The sonographic feature of brain tumor is a hyperechoic or hypoechoic mass with well-defined or unrecognized border. Intracranial teratoma appears as heterogeneous echogenicity with calcification and cystic lesion. Ependymoma presents as a large cystic mass. Choroid plexus papilloma is hyperechoic on ultraso-nography and located in the lateral ventricles [1011].

In other case reports, sonographic pattern of ETMR was not described in detail. The sonographic feature of this case show as a heteroechogenic mass with poorly differentiated border from adjacent structures which is comparable with the manifestation of MRI. In the midline sagittal view, vermis of cerebellar should be visualized, however, the margin of vermis was not clear and cistern magna was not remarkable in this case (Fig. 1b). There was no cystic or calcification lesion on ultrasonography. Nevertheless, small cystic components of tumor were seen in MRI (Fig. 2). The image quality of ultrasonography is usually insufficient to investigate the morphology of space-occupying lesions, e.g. intracranial hemorrhage can also mimic brain tumors. Further laboratory examinations and imaging studies are warranted.

In conclusion, we presented a case of one rapid growth ETMR in a neonate with enlarged head girth. Transcranial Doppler ultrasonography is the first-line tool that may help use to evaluate baby with unclosed fontanel. Space-occupying lesion may obstruct the CSF pathway especially in the localized infratentorial area. Careful examination of structure of brain which presented as hydrocephalus is important. Prognosis of ETMR remains dismal [12].