A Treatise on Pediatric Meningiomas: Single-center Retrospective Cohort Experience and Review of Literature

ABSTRACT

Background:

Pediatric meningiomas are infrequently encountered in clinical practice. In comparison to adults, they have a distinct pathophysiology and clinical presentation. They are benign but locally aggressive tumors. Radical excision often culminates in good outcome.

Aim:

The aim of this study was to study the demographic profile, clinico-radiological features, pathophysiology, and surgical outcome of childhood meningiomas.

Materials and Methods:

The case records of patients <18 years of age operated for meningiomas in our institute from 1985 to 2015 were retrieved. The demographic profile, clinical and radiological features, surgical approach, extension of resection, and surgical outcome were recorded and subsequently analyzed.

Results:

Among 37 patients, 20 were males and 17 were females. The mean age was 13 years. Predisposing etiologies such as neurofibromatosis and radiation exposure were identified in 20% of the study population. There were 31 intracranial and 6 spinal meningiomas. Headache associated with vomiting was the most common presenting complaint. Majority were supratentorial tumors. A safe maximal excision was attempted in each case. Recurrence was noted in five patients. Average follow-up was approximately 24 months. Two patients succumbed to the illness. Approximately, 30% of patients were rendered morbid.

Conclusion:

Although rare, pediatric meningiomas are biologically different from their adult counterparts. They have a male predominance, common in intraventricular region and cystic in nature. Radical excision is associated with good prognosis. Although benign, they are aggressive in nature and have a tendency to recur. The response to adjuvant therapy is modest. Further molecular research and genetic studies are necessary to understand the biology of pediatric meningiomas, which will help in the identification of targeted molecular therapy.

INTRODUCTION

Meningiomas are second to gliomas in terms of frequency of occurrence in adults. However, pediatric meningioma is a rare entity. They account for 0.4%–4.6% of all primary childhood brain tumors.[1] There is definite role of predisposing factors such as previous radiation exposure and presence of neurofibromatosis (NF) in development of these tumors.[2] There is slight male predominance noted with an average sex ratio of 1.2:1, unlike their adult counterparts.[1] They are generally benign in histology, but locally aggressive. Total radical excision often portends to good outcome in this population.

MATERIALS AND METHODS

A retrospective analysis of all patients under 18 years of age operated and treated for meningiomas in the King Edward Memorial (KEM) Hospital, Mumbai, Maharashtra, India, since 1985 till 2015 was performed. Information encompassing clinical presentation, radiological features, operative technique, operative finding, and histopathological correlation was documented. Follow-up with emphasis on morbidity and mortality quotients was recorded. A special note of discriminating features from their adult counterparts was made whenever feasible.

Statistical analysis was carried out in Microsoft Excel, Microsoft Corporation, Redmond, WA after due compilation of the data. Measures of central tendency such as mean and median were typically used.

RESULTS

The demographic profile, clinico-radiological features, histopathology, and surgical outcome of pediatric meningioma patients have been studied.

A total of 37 patients formed our study group. The sex ratio was 1:1.2 with 17 females and 20 males. The average age at presentation was 14 years. The age spectrum spanned across from 2.5 to 20 years.

Anatomical distribution

There were six cases of spinal meningiomas and 31 patients of intracranial meningiomas [Figure 1]. There were approximately four cases of orbital meningiomas. There were three children with petroclival meningioma.

Figure 1.

Right anterior clinoidal meningioma: (A) preoperative axial T1 CT image postcontrast showing right anterior clinoidal meningioma, (B) preoperative axial T2-weighted magnetic resonance image showing right anterior clinoidal meningioma, and (C) postoperative axial CT image postcontrast showing partial staged resection of the lateral portion of the meningioma

Of the supratentorial tumors, parietal convexity meningiomas formed the majority [Figure 2]. The supratentorial meningiomas have been subclassified based on the anatomical location [Table 1]. There were only two cases of infratentorial meningiomas [Figure 3].

Figure 2.

Right frontoparietal meningioma: (A) preoperative axial CT image postcontrast showing right frontoparietal convexity meningioma and (B) postoperative axial CT image postcontrast showing radical resection of the meningioma

Table 1.

Anatomical subclassification of supratentorial pediatric meningiomas

Tumor location	Frequency (%)
Orbital	4 (10.8)
Skull base meningioma	8 (21.6)
Convexity meningioma	17 (67.2)

Figure 3.

Preoperative image of a patient with foramen magnum meningioma: sagittal T1-weighted magnetic resonance image showing foramen magnum meningioma

Clinical presentation

Majority of children presented with signs and symptoms secondary to raised intracranial pressure. The presenting complaints with their relative frequencies have been summarized in Table 2.

Table 2.

Clinical presentation

Complaint	Frequency (%)
Headache	70.2
Vomiting	70
Convulsion	13
Diminution of vision	11
Paresis	10

Predisposing factors

NF was the most frequent inciting etiology and was present in approximately 16% of patients. Radiation exposure as part of treatment for ALL (acute lymphocytic leukemia) was present in one patient.

Radiological features

The majority of patients from 1985 to 1990s have computed tomographic (CT) images.

There were 15 partially cystic meningiomas. Approximately, 10 patients had intraventricular tumors. The heterogenous contrast enhancement and necrosis implying aggressiveness and higher potential for recurrence were noticed in 12 patients.

Surgical details

A complete radical resection was attempted in every patient in our series. Simpson’s grade II was achieved in majority of cases. Preoperative embolization to preemptively decrease the vascularity of the tumors was performed in two patients. The dural attachment was identified and coagulated in every patient. Planned staged surgery was carried out in two patients. There were three patients who were operated outside and had to be reoperated to achieve maximum safe resection.

Approximately, eight patients developed recurrent tumors and had to undergo resurgery. Majority of the meningiomas in our series were histopathologically benign transitional meningiomas.

Morbidity

In the immediate postoperative period, majority of the patients improved in their preoperative symptoms. There were postoperative convulsions in 16 patients; most of which were managed conservatively. There were 10 patients with immediate postoperative limb weakness; majority of whom improved over a week’s time with cerebral decongestants.

Major morbidity in the form of residual postoperative limb weakness was encountered in six patients. Approximately, 80% of these showed significant improvement in power at 6 months of follow-up. Persistent headache was seen in five patients. There was postoperative cranial nerve paresis in three patients with petroclival meningiomas. All of them had undergone multiple surgeries. The facial paresis improved in two of these patients. There was no improvement in the vision of patients with orbital meningiomas.

Mortality

The mortality rate of our series was 5.4%. Of the two patients who died, one child was a 12-year-old girl who was operated four times for petroclival meningioma, twice at our institute. She had preoperative history of convulsion and right-sided limb weakness. She had left trigeminal and facial nerve paresis. During her third surgery, she developed intraoperative autonomic disturbances and the surgery was abandoned. She went into status epilepticus postoperatively and could not be salvaged. Histopathology was fibroblastic meningioma.

The second pediatric patient who expired was a 2.5-year-old baby girl with left frontal falcine meningioma. She presented with bilateral lower limb weakness for 3 months and bladder incontinence for 1 month. She had major blood loss intraoperatively, which was adequately replaced. In the postoperative period, she developed pulmonary edema and succumbed to the same.

Histopathology

The most frequent histopathological diagnosis in our series was transitional meningioma as shown in 23 of 37 patients. Malignant angiomatous tumor was documented in two patients. The various histopathological classes of meningiomas encountered in our pediatric population with their relative frequencies have been mentioned in Table 3 and Figure 2.

Table 3.

Histopathological distribution of pediatric meningiomas

Histopathology	Frequency (%)
Transitional meningioma	23/37 (62.16)
Fibroblastic meningioma	4/37 (10.8)
Papillary meningioma	4/37 (10.8)
Malignant angiomatous tumor	2/37 (5.4)
Vascular meningioma with reactive bone changes	1/37 (5.4)
Myxomatous meningioma	1/37 (5.4)
Syncytial meningioma	2/37 (5.4)

DISCUSSION

Pediatric meningiomas are infrequent primary brain tumors. The incidence is estimated to be approximately 0.5%–3% of all pediatric brain tumors.[1,2,3] They behave differently as compared to their adult counterparts. The largest series on pediatric meningiomas is from the Netherlands. Thuijs et al.[4] reported 72 patients of pediatric meningiomas in over 35 years of experience. Our series consisted of 37 patients, studied over 29 years.

Adult meningiomas are most commonly encountered in the fifth and sixth decades of life. Most childhood meningiomas are described in the late first and early second decade of life, as reported by Perry and Dehner.[5] Consistent with the aforementioned findings, the mean age of presentation in our study was 14 years.

Our study population comprised 20 males and 17 females. The male-to-female ratio was 1.2:1. The slight male predominance is reflected in many other pediatric meningioma case series.[1,3,4] Unlike pediatric meningiomas, female preponderance in adult meningiomas is linked to the interplay of sex hormones on corticosteroid receptors in the arachnoid cap cells.

There are other mechanisms at play in the pathogenesis of pediatric meningiomas. Begnami et al.[6] have confirmed the role of NF2 gene in tumorigenesis of pediatric meningiomas. They reported NF2 gene deletion with decreased merlin protein expression in as many as 72% of the patients. NF was present in approximately 16% of our patients.

We report approximately six cases of spinal meningiomas and 31 cases of intracranial tumors. Thoracic region is the most common location of spinal pediatric tumors as reported by Baumgartner and Sorenson.[7] This is in accordance with our study. Wang et al.[8] studied approximately 10 cases of spinal meningiomas from 2003 to 2012. They reported worse prognosis in children with NF. Approximately, 50% of our patients with spinal meningiomas had NF. There were preoperative motor deficits in two of them. They showed minimal postoperative improvement. We concluded that absence of predisposing factors such as NF translates in better outcome. Santos et al.[9] shared similar opinion.

Infratentorial meningiomas were found in only 5.4% of patients, with the majority being supratentorial tumors. The most frequent tumor was the parietal convexity meningioma. Baumgartner and Sorenson[7] reported an incidence of approximately 83% of supratentorial tumors. The incidence of supratentorial tumors in our series was 78.3%.

The most common complaints in the pediatric age group with meningiomas reflect features of raised intracranial pressure. Headache and vomiting were seen in approximately 70% of children. Maranhão-Filho et al.,[10] in a study on seven patients with pediatric meningiomas, concluded that headache, seizures, and motor deficits were the most frequent complaints on presentation. Pediatric meningiomas are locally aggressive and often found in intraventricular location, which can explain the propensity to block the cerebrospinal fluid pathways earlier, leading to premature development of hydrocephalus and raised intracranial pressure in these patients. This is in accordance with Mehta et al.,[1] who cited similar findings.

Maximal safe resection as advocated in majority of series on pediatric meningiomas was attempted in every patient. Approximately, eight patients had to undergo staged procedures to reach complete maximum safe resection. The intraventricular nature, attachment to the base of the skull, and cystic nature made radical excision difficult in some of these tumors. Dash et al.[11] have described absence of dural tail in intraparenchymal pediatric meningiomas. The dural tail was identified in most of our patients.[12]

The most frequently encountered meningioma in our series was benign transitional meningioma. The benign histopathological nature did not always mean good prognosis. In our series, the patient of malignant angiomatous meningioma who underwent complete resection had a good outcome. On the contrary, a patient with histopathologically benign grade petroclival meningioma succumbed. Secondary to the arduous location of the meningioma, this patient had undergone multiple surgeries, the last one being for recurrence.

There were eight patients who underwent multiple surgeries with documented recurrence in five of them. Majority were patients with skull base meningiomas [Table 4]. The possible explanation due to the skull base location is that they often defy rules of complete resection. Subtotal resection has been repeatedly proven to lead to recurrence and worse prognosis. Burkhardt et al.[13] reported that skull base meningiomas have relatively poor prognosis as they are less likely to yield to maximally safe radical resection. Ravindranath et al.[14] concluded that resurgery often with adjuvant radiotherapy helps in recurrent cases.

Table 4.

Stratification of tumor behavior and its management as per location

Location	Feature
	Recurrence (5)	Redo-surgery (8)	Preplanned staged surgery (2)
Skull base meningioma (8)	5/5 (100%)	6/8 (75%)	2/2 (100%)
Supratentorial convexity lesions (17)	None	2/8 (25%)	None
Infratentorial/foramen magnum meningiomas (4)	None	None	None

The single most defining prognostic factor is extent of resection. The location and ability to completely resect the tumor help prognosticate better than the histopathology. This concurs with the findings of Menon et al.[2]

The presence of predisposing etiologies such as NF and radiation exposure leads to worse prognosis. The intraventricular and base of skull location with cystic nature of some of these tumors leads to partial excision, which then translates into eventual recurrence. These are more relevant prognosticating factors as compared to the histological grade.

Menon et al.[2] have scanned data from 1882 to 2009. They have described younger age (<10 years), superficial position, complete resection, and absence of predisposing conditions (such as NF) as indicators of positive outcome. They concluded that the extent of resection predicts outcome better than the histopathological grade. The same can be appreciated in our study, as the lesions that behaved locally and clinically aggressive were in fact benign on histopathology.

Santos et al.[9] have concluded in the same vein that the presence of predisposing situations such as radiation and NF along with the extent of resection affects the prognosis more than the histopathological grade.

The mean follow-up was approximately 24 months. Adjuvant radiation therapy was advocated for patients older than 3 years, with residual lesion, recurrence, or higher histopathological grade. Four patients received radiation. Owing to limited follow-up, we cannot prognosticate for these patients in the long run. We acknowledge that scarce follow-up data are a major limitation of our study.

A brief comparative review of the major series of pediatric meningiomas published till date is presented in Table 5.

Table 5.

Review of literature

Series	Sample size	Observations and implications
1. Mehta et al.[1]	18	Male preponderance
		Relatively higher intraventricular tumors, frequent cystic changes, most common mode of presentation being raised intracranial pressure with systemic features such as headache and vomiting, in pediatric meningioma patients compared to adults.
		Total surgical resection should always be the aim.
		Atypical and aggressive histopathological patterns are more frequently discerned in pediatric patients.
		Patients with complete excision of benign tumors have good prognosis as in adults.
2. Baumgartner and Sorenson[7]	14	Similar observations to Bhagwati et al.
		They reported that pediatric meningiomas tend to be more aggressive compared to their adult counterparts.
		Recurrence rate of pediatric meningiomas is higher.
		In addition, they identified neurofibromatosis and radiation as significant predisposing factors.
		Treatment protocol of children with neurofibromatosis and meningiomas and those with subtotal resection has no unequivocal single answer
3. Thuijs et al.[4]	72	Approximately 25% of pediatric meningiomas show aggressive behavior, which calls for adjuvant therapy.
		5-year survival rate is 83.9%
4. Santos et al.[9]	15	Male predominance
		Presence of radiation, neurofibromatosis, location, and extent of resection are more relevant prognosticating measures than the histopathological grade.
5. Burkhardt et al.[13]	12	Skull base meningiomas, albeit being smaller were difficult to resect completely and subsequently had worse prognosis.
6. Menon et al.[2]	38	Skull base meningiomas and tumors with atypical histopathology are more frequently encountered in the pediatric population. Positive prognosticating factors were identified as younger age (<10 years), superficial location, complete resection, and absence of predisposing conditions such as neurofibromatosis. They moved to make a stronger conclusion, namely that the extent of excision has higher positive predictive value for good outcome than even the histopathological grade.
7. Dash et al.[11]	6	Dedicated to intraventricular pediatric meningiomas; this series elaborated upon the parieto-occipital transcortical, transcallosal approach, and the middle/inferior temporal gyrus approach for such tumors.
8. Ghim et al.[3]	15	This is a unique study concentrating on pediatric meningiomas after radiation. They proposed that such tumors are mainly calvarial in nature, mostly benign and often give themselves in to complete resection.
9. Maranhão-Filho et al.[10]	7	Most of pediatric meningiomas are low grade and have a good prognosis. They had zero mortality. Headaches, seizures, and motor deficits were the most common presenting complaints.
10. Wang et al.[8]	10	Based in China, Wang et al. studied 10 patients of spinal meningiomas. They concluded that spinal meningiomas in pediatric population, especially those associated with neurofibromatosis have worse prognosis.
11. Hanel et al.[15]	2	Pediatric meningioma is an infrequent but relevant differential for any expansive intracranial lesion.
12. Alexiou et al.[16]	8	Reviewed over 16 years, Alexiou et al. concluded that gross total resection best determines the final outcome.
13. Sheikh et al.[17]	9	The meningothelial variant of meningioma was reported to be the most common. Tendency for rapid growth and expansion, malignant transformation, and greater rate of recurrence were cited as reasons for poor prognosis in children as compared to adults.
14. Arivazhagan et al.[18]	33	They concluded similarly in terms of male predominance and worse prognosis when associated with neurofibromatosis. They opined that atypical location makes surgical management challenging.
15. Gao et al.[19]	54	A large series from China, they concluded in a concurrent manner to the above mentioned studies.
16. Erdinçler et al.[20]	29	They recorded that absence of dural attachment is more frequently seen in this age group. Association with neurofibromatosis was upheld to be the most important factor influencing outcome.
17. Ravindranath et al.[14]	31	Sharing similar demographic profile as ours; this study documented use of radiotherapy as a good adjuvant. They also studied their recurrence rate and reported that resurgery and radiotherapy in such cases often portends good outcome.

Implications

Our study pertaining to our single-institute experience revealed data akin to other major contemporary pediatric meningioma series. This reinforces and consolidates our strategy on the management of these patients at our institute. We do not favor multiple stage surgeries where maximum safe radical resection can be performed. We do not practice preoperative shunt insertion. We favor more of operative management rather than wait and watch management with symptomatic treatment, even for dangerous terrains such as skull base and petroclival regions. Our results have been good and at par with other institutes.

CONCLUSION

Although rare, pediatric meningiomas are biologically different from their adult counterparts. They have a male predominance, common in intraventricular region, and cystic in nature. Radical excision is associated with good prognosis. Although benign, they are aggressive in nature and have a tendency to recur. The response to adjuvant therapy is modest. Further molecular research and genetic studies are necessary to understand the biology of pediatric meningiomas, which will help in the identification of targeted molecular therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.