Paediatric Rhabdoid Meningioma: Clinical and Therapeutic Features Findings – Case Series of 3 Patients

Abstract Introduction: Paediatric rhabdoid meningioma (RM) is the rarest but most aggressive subtype of meningioma, related to a severe prognosis. They account for 1–3% of all intracranial meningiomas. Case Presentations: We report an institutional experience of 3 cases through which we discuss clinical, histological, and therapeutic features of this tumour. Two of our patients were female-gendered (3 years old and 1 year and 6 months old), and one was male-gendered (16 years old). Revealing symptoms were related to intracranial hypertension, cerebellar syndrome, cranial nerve palsy, and skull tumefaction. Imaging showed extra-axial tumour located in the right ponto-cerebellar angle in the first case, in the left occipital region in the second case, left parietal tumour in the third case. All patients underwent a surgical intervention with a gross total resection. Histological evaluation supported by immunohistochemistry confirmed the diagnosis of RM. Tumour recurrence was observed at 45 days in the first case with a fatal outcome. Despite adjuvant radiotherapy, both second and third cases had local recurrence after a mean follow-up of 1 month following the radiotherapy. Conclusions: RM is very aggressive tumours. Standardized therapeutic guidelines are still under debate as actual approaches are still inefficient to prevent quick recurrence and fatal outcome. Established Facts Paediatric rhabdoid meningiomas are rare but aggressive subtypes of meningioma. They are related to severe prognosis.


Introduction
Brain tumours are the most common solid malignancies in childhood [1,2].Multiple variants of primitive brain tumours with disparate aetiologies, morphologies, prognoses, and responses to adjuvant therapies may arise in the paediatric group [1,3].Within these tumours, meningiomas are infrequent as they are commonly encountered during the adulthood.When they occur in the childhood, meningiomas are usually related to particular risk factors, mainly following radiotherapy, skull fracture, or in type 2 neurofibromatosis [4,5].Paediatric rhabdoid meningioma (RM) is the rarest but most aggressive subtype of meningiomas, responsible for severe prognosis and outcome [1,2,6].They account for 1-3% of all intracranial meningiomas [2,6,7].Herein, we report a small series of 3 cases of paediatric RMs.Based on these cases, we went through a review of the literature in order to discuss clinical, histological, and therapeutic features of this tumour.

Case Presentations
We report an institutional experience of the management of 3 children, who were operated in the neurosurgical department of the Trauma and Burns Center in Ben Arous during the period ranging from October 2012 to October 2021.Clinical, radiologic, and therapeutic data were studied retrospectively.
Case 1 A 3-year-old girl, with no pathologic background, presented due to the progressive onset of signs of intracranial hypertension.Physical exam found a fully conscious child, who had a right cerebellar syndrome associated to a right facial palsy.Otherwise, there were no abnormalities at exam that could evoke a neuro-fibromatosis.Brain MRI showed an extra-axial tumour of the right ponto-cerebellar angle (Fig. 1).The patient underwent surgery with a gross total resection.Postoperative course was uneventful, and control brain CT scan (Fig. 2) showed no evidence for tumour residue.The patient was discharged 4 days postoperatively.Histological exam supported by immunohistochemistry (Fig. 3) confirmed the diagnosis of RM as it showed sheets of cells with variably abundant eosinophilic cytoplasm, eccentric nuclei, and hyaline para-nuclear inclusions.Vimentin, cytokeratine, and EMA were positive.
One month following surgery, the patient presented a recurrence of the headaches.Control CT scan (Fig. 4) showed a local tumour recurrence.The patient was reoperated on 45 days after the first surgery.She presented postoperative haemodynamic instability and died on the first day following the reintervention.

Paediatric Rhabdoid Meningioma: Clinical and Therapeutic Features Findings
Case 2 An 18-month-old girl, who had no previous medical conditions, was admitted due to a progressive development over 2 months of a left occipital tumefaction (Fig. 5).Physical exam found a rounded non-mobilizable left occipital solid mass measuring 7 × 5 cm.There were no inflammatory signs regarding the mass, and palpation did not trigger any pain.Otherwise, no neurological signs of localization or of intracranial hypertension were found or reported.Brain MRI (Fig. 6) showed a left occipital extra-axial with double extension towards sub and infra-tentorial areas and was responsible for a bone destruction with both endo and exocranial extensions.The patient underwent surgery for a gross total excision of the mass (Fig. 6).Postoperative course was uneventful and the patient was discharged on the fourth postoperative day.Histological evaluation supported by immunohistochemistry confirmed the diagnosis of RM.The patient had an adjuvant radiotherapy.After a 1-year follow-up, the patient did not present any clinical or radiologic features indicating a tumour recurrence.

Case 3
A 16-year-old boy, without any pathologic background, presented with a history of intracranial hypertension signs with a progressive onset since 2 months.Physical exam found a fully conscious patient, who had a paralysis of the sixth left cerebral nerve without any other neurologic signs of localization.Brain MRI showed a left extra-axial parietal tumour.The patient underwent surgery for a gross total resection of the tumour (Fig. 7).Postoperative course was uneventful, and the patient was discharged on the fourth day following surgery.Histological evaluation supported by immunohistochemistry confirmed the same diagnosis as the first two cases, namely, a RM.On follow-up, the patient did not present any recurrence of the neurologic signs.But a brain imaging performed 2 months postoperative showed a recurrence of the mass within the same location.Thus, the patient underwent a second surgery, followed by an adjuvant radiotherapy.Oneyear follow-up showed neither clinical nor radiologic signs of recurrence.Gader/Slimane/Sliti/Badri/Zammel

Discussion
The observations of the malignant histological features and reported aggressive behaviour with a higher rate of recurrence of RM led to its classification most recently by WHO (2000) as a grade III neoplasm [8][9][10][11].RM is a rare subtype of meningioma, accounting for 1-3% of all intracranial meningiomas [7].The mean age of presentation is 51 years with a sex ratio of 4/3.A review of the literature on RM showed that recurrence occurs in more than 50% of the patients [12].Germano et al. [7] shared their experience with meningioma of the first 20 years of life and reviewed 14 series of patients, with total number of 278 cases, and showed an incidence of paediatric meningioma ranging from 1 to 4.2% of all meningiomas.Meningiomas of the adulthood predominate in women.This is not the case in paediatric meningiomas where no female predominance is found [7].Some factors have been reported to be in correlation with a high risk of onset of menin-giomas in children: hormonal factor, radiation, genetic factors (approximately 20-40% of children with meningioma have neurofibromatosis type 2, especially those with multiple tumours and familial meningioma), and head trauma [4,13,14].Clinical presentation in children is represented by focal neurological deficits (33%), seizures (25%), and symptoms of raised intracranial pressure (25%) [7].70% of paediatric meningiomas are supratentorial (70%).Rhabdoid tumours are very rare in the childhood, as to the best of our knowledge, only 20 cases have previously been reported in the literature.Clinical features of 20 juvenile cases of RMs are summarized in Table 1.RM has first been described in 1978 by Beckwith and Palmer [15] and was reported to present multiple similarities with aggressive renal tumours and associated to a poor outcome.RM is histologically defined by the presence of abundant eosinophilic cytoplasm, eccentric nuclei, and intracytoplasmic hyaline inclusions [16,17].Rhabdoid cells by themselves are not anaplastic only if they show signs  Paediatric Rhabdoid Meningioma: Clinical and Therapeutic Features Findings of necrosis, high mitosis, atypia, sheeting, elevated MIB-1, and brain invasion.Staining varies in degrees in EMA, vimentin, and cytokeratine [16,18,19].The diagnosis requires a detailed study and exclusion of other differentials due to a difficulty distinguishing malignant meningiomas from primary meningeal sarcomas [20].Therefore, the role of positive EMA will suggest meningioma and sarcoma herringbone architecture [16].One interesting feature of RM is that, in a significant number of cases, the rhabdoid cells appear after an initial recurrence.The exact causes of rhabdoid transformation from a benign meningioma are currently unknown [18,21].Concerning therapeutic approach, it is actually admitted that the treatment of atypical and malignant meningiomas is based on radical surgery with the aim to obtain a Simpson grade I resection [22].Preoperative embolization aiming to reduce peroperative bleeding and the risk of embolic stroke and haemorrhage into a necrotic tumour should be considered in voluminous and hypervascularized tumours [23,24].Early conventional radiotherapy is recommended for atypical and anaplastic meningiomas regardless the Simpson grade, with many studies showing improved disease-free survival.Recent studies suggest that Gamma Knife radiosurgery may be a useful adjuvant therapy tool.Patients most likely to benefit are those with smaller tumours [25].Median survival exceeding 5 years with combined radiochemotherapy has been reported [26].This seems to be mainly related to radiotherapy as studies proved that chemotherapeutic regimens are not very effective against atypical/anaplastic meningioma [27,28].The outcome of the reported juvenile RMs seems to be better than their adult counterparts, in which mortality rate was of 49.2% after a mean follow-up of 1 year [12].Prognosis seems to be related to the quality of surgical

Fig. 1 .
Fig. 1.Brain MRI on coronal section T1weighted imaging with injection of Gadolinium (a) and axial section of a T2-WI (b) showing an extra-axial lesion developing within the right ponto-cerebellar angle with an attach on endocranial part of the petrosal bone.This lesion is responsible for a compression of the cerebellum and the brainstem.

Fig. 2 .
Fig. 2. Axial section of a postoperative CT scan showing a complete removal of the tumour.

Fig. 3 .
Fig. 3. a, b Histological images with haematoxylin-eosine colouration.a 10 times enlarged showing a diffuse tumoural proliferation.b Curved tumoural cells with eosinophile cytoplasm containing excentred vesiculous nuclei, concordant with a rhabdoid aspect.c Immunohistochemistry shows that tumour cells are strongly positive to EMA.

Fig. 4 .
Fig. 4. Axial section of a control CT scan showing the recurrence of the tumour.

Fig. 6 .
Fig. 6.Brain MRI on axial (a, b) and coronal (c) sections, on T1-WI without injection of gadolinium (c), with injection of gadolinium (a) and on T2-WI showing an extra-axial left occipital lesion destroying the occipital bone with both intra-and extra-cranial extensions.

Fig. 7 .
Fig. 7. Peroperative pictures of the surgical field before and after resection of the tumour.

Table 1 .
Representation of paediatric cases of RMs reported in the literature