16 MONTH‐OLD FEMALE WITH INTRAVENTRICULAR MASS

CLINICAL HISTORY

A 16 month old female was admitted to the Pediatric Intensive Care Unit with fever, hypoxia, altered mental status, and seizures. Magnetic resonance imaging (MRI) of the brain (Figure 1) showed a single well circumscribed intraventricular mass which was isointense to cortex on T1‐and T2‐weighted images, and demonstrated mildly restricted diffusion consistent with dense cell packing. The mass measured 4 × 4 × 4 cm in the craniocaudal, AP and transverse dimensions. FLAIR imaging revealed mass effect secondary to the tumor causing trapping of the left temporal horn. There was additional, but mild right lateral ventricular dilatation and an 11 mm midline shift as measured at the level of the anterior portion of the third ventricle. Edema was seen along the corpus callosum, surrounding the mass extending into the left occipital lobe, temporal lobe, and parietal lobe.

Figure 1.

The patient subsequently had surgical resection of the mass with MRI navigation guidance. Intraoperatively the mass had a thick capsule and a rubber‐like core. The entire tumor was removed without intraoperative complications. The patient was discharged home 4 days later and has done well since that time with no neurological deficits.

PATHOLOGY

H&E stained sections showed a cellular tumor (Fig 2a) with areas of geographical necrosis (Fig 2b). Also observed were macronuclei and a relatively high mitotic rate (13 mitoses per 10 high power fields). Immunostains for Ki‐67 showed a proliferation index estimated at 30–40% (Fig 2c) and focal immunoreactivity for epithelial membrane antigen (EMA) (Figure 2d). No cytokeratin or GFAP immunoreactivity was observed.

Figure 2.

Due to the atypical radiological and pathological characteristics, a syndromic association was sought. This included a comprehensive NF2 mutation analysis on the pathological tissue. This analysis revealed two pathogenic mutations in the neurofibromatosis type 2 (NF2) gene; a 169C>T truncating mutation leading to a premature stop codon and a total NF2 gene deletion. Since the patient had no immediate family history of NF2, further genetic analysis was indicated to verify whether there was an NF2 germline mutation (NF2 Test 2). Singleton cases as this can reveal mosaicism in a constitutional blood study. Analysis of the patient's constitutional lymphocyte DNA revealed the same truncating NF2 mutation and thus the patient was diagnosed with NF2. The child's parents underwent extensive genetic counseling and were encouraged to undergo NF2 mutation analysis as both are in their early twenties and could have pre‐symptomatic NF2.

DIAGNOSIS

Congenital Intraventricular Atypical Meningioma, WHO grade 2 leading to a genetic diagnosis of NF‐2

DISCUSSION

Childhood meningiomas are a rare entity accounting for about 1.5% of all pediatric intracranial tumors as compared with adults where they constitute nearly one third of such masses (10). While in adults, meningiomas occur in the ventricular system in only 2% of the cases; the number of ventricular lesions in children is four to ten times higher 4, 5. Thus, even though they are rare, pediatric meningiomas often pose a challenge to neurosurgeons. This report provides an interesting case of an unusually large atypical intraventricular meningioma in an infant.

According to the criteria set by the WHO panel, diagnosis of atypical meningioma should be made when the tumor has an average mitotic rate of >4 per 10 hpf, or has 3 of the following 5 features: tumor necrosis; sheet‐like patternless growth; small cells with high nucleocytoplasmic ratio; and hypercellularity. Two types of meningiomas, chordoid and clear cell, typically fit these criteria. In a recent review of 8 cases of childhood meningiomas, 2 were diagnosed as atypical with the youngest patient being 3 years old (1). In general, histopathology in childhood meningiomas shows a preponderance of grade I (>70%), with atypical being 2–4% and grade III as less than 5%. Atypical meningiomas however, have been reported to be as high as 20% in at least one case series (6).

Meningiomas in children are usually associated with NF2 or previous cranial irradiation. Perilongo et al (7) reported that 23% of patients had evidence of NF2 (8). Genetic testing for patients suspected of NF2 follows a sequence beginning with tumor cell DNA analysis in cases such as ours. If tumor cell DNA analysis shows NF2 mutations in both alleles, a study of the patient's constitutional DNA is indicated to look for a germline mutation. Of note is that germline nonsense NF2 mutations, such as seen in our patient, are associated with increased disease severity and an increase in the number of NF2‐associated intracranial meningiomas (2) Constitutional nonsense and frameshift NF2 mutations are associated with severe, and missense mutations and somatic mosaicism are associated with mild disease 3, 9.

The current case illustrates an unusually large, congenital, intraventricular meningioma of atypical pathology in an infant. Given the age at presentation and the presence of constitutional NF2 mutations, this child is likely to eventually develop the multiple other lesions associated with the syndrome. The patient will, therefore, undergo early hearing testing, routine eye examinations and MRI screening for vestibular, other intracranial and spinal lesions starting at age 5 years (2).

ABSTRACT

Pediatric meningiomas are rare and account for about 1.5% of all intracranial tumors. When compared to adults, intraventricular location of childhood meningiomas is four to ten times as high. Atypical pathology of these lesions is very uncommon and indicates an aggressive nature. They are usually associated with Neurofibromatosis 2 (NF2) or previous cranial irradiation. Here, we present an interesting case of an unusually large, congenital intraventricular meningioma of atypical pathology in a 16 month old child with subsequently diagnosed NF2. A brief review of literature is also presented with this case illustration.