Histomorphological Spectrum of Pediatric Supratentorial CNS Tumors: A 3-year Retrospective Study in a Tertiary Care Center.

Objective: Central nervous system (CNS) tumors are the second most common neoplasms in children and they differ from their adult counterparts in terms of incidence, topography, clinical features, histology, and outcome. This article analyzes the incidence of supratentorial tumors, various histopathological entities, and their characteristics in pediatric patients <18 years of age. Materials and
Methods: This was a retrospective study conducted at the Department of Neuropathology, Institute of Neurosurgery, MMC/RGGGH Chennai from January 2017 to December 2019. Data of supratentorial tumors in children less than 18 years of age procured and their histomorphological profile were analyzed.
Results: In our institution, of a total of 1134 CNS and spinal neoplasms, 117 pediatric intracranial and 7 spinal neoplasms were reported and the incidence of supratentorial pediatric tumors was 44.44% (52 cases). Among which intraaxial tumors account for 38.46% with 20 cases, extraaxial tumors 51.92% with 27 cases, and intraventricular tumors 9.61% with five reported cases. Most common tumors reported were astrocytomas, craniopharyngioma, followed by ependymoma among others.
Conclusion: Though posterior fossa neoplasms are more common in children, supratentorial tumors show a rising trend worldwide in the pediatric population. Our study gives an overview of the incidence and histopathological profile of supratentorial CNS tumors. Copyright:

INTRODUCTION

Central nervous system (CNS) tumors constitute the second most frequent childhood neoplasm next to leukemias and remain the most important cause of morbidity and mortality in children. They show considerable variation in terms of anatomical location, clinical presentation, histological features, and prognosis compared with adults. Intracranial neoplasms in children significantly affect their quality of life and they predominantly present with features of increased intracranial pressure such as lethargy, increase in head circumference, vomiting, and headache. Although infratentorial tumors are more common in children, supratentorial tumors show a diverse histological pattern. Glial neoplasms encompass the most common supratentorial intraaxial tumors and include pilocytic astrocytoma, oligodendroglioma, glioblastoma, pleomorphic xanthoastrocytoma (PXA), subependymal giant cell astrocytoma (SEGA), and the predominant extraaxial tumors include craniopharygioma, pituitary adenoma, and meningiomas. Choroid plexus tumors and ependymoma contribute to supratentorial intraventricular tumors in children.

In India, there are very limited published data on the epidemiological profile of pediatric supratentorial tumors. This study attempts to analyze in detail the incidence and categorize the histomorphological patterns of pediatric supratentorial neoplasms in accordance with World Health Organization (WHO) classification 2016 and the data compared with Indian and International statistics.

SUBJECTS AND METHODS

This is a retrospective study wherein data on supratentorial CNS neoplasms in the pediatric age group (<18 years) were collected and histological slides reviewed from January 2017 to December 2019. Immunohistochemistry was used where necessary and the cases categorized as per the 2016 WHO classification.

Inclusion criteria

All histologically proven supratentorial neoplasms including intraaxial, extraaxial, and intraventricular tumors were included in the study. The pediatric age group was further subcategorized into 0–2 years, 3–6 years, 7–12 years, and 13–18 years as per WHO standards. The age categorization is usually done to better understand the incidence and behavior of various tumors in children and adolescents

Age, sex, clinical presentation, site of lesion, and histopathological findings were recorded and a comprehensive analysis was done.

Exclusion criteria

Primary brain tumors arising from the infratentorium, space-occupying lesions of infective etiology, benign cystic lesions, metastasis, and other developmental and vascular malformations were excluded from the study.

RESULTS

In our institution, of the total 1134 CNS and spinal cord neoplasms, pediatric CNS and spinal tumors were 124 cases with exclusive pediatric intracranial tumors accounting for 117 cases with an incidence of 10.31%. Supratentorial tumors accounted for 44.44% (52 cases) and infratentorial tumors 55.55% (65 cases).

Distribution based on age and gender

There were 33 males (63.46%) and 19 females (36.53%) in the study group with a male: female ratio of 1.7:1. Majority of supratentorial CNS tumors were common in the age group of (13–18) years constituting 44.23% and least common in (0–2) years age category (13.46%) [Figures 1 and 2].

Figure 1

Distribution based on gender

Figure 2

Distribution based on age

Distribution based on location

Of the 52 supratentorial tumors, 20 cases were intraaxial with an incidence of 38.46%, 27 cases were extraaxial (51.92%), and 5 cases intraventricular with 9.61% [Figures 3 and 4].

Figure 3

Compartmental distribution

Figure 4

Distribution based on location in relation to gender

Distribution based on histological subtypes and WHO grading

The number and percentage of various histological subtypes of supratentorial location are summarized in Table 1. The most common neoplasms were Astrocytic tumors accounting for 26.92%, followed closely by craniopharyngioma with an average of 25% and ependymomas accounting for 15.38%. Figure 5 depicts glial and glianeuronal tumours percentage distribution.. The tumors were graded as per the 2016 WHO classification. Of the total 52 cases, WHO grade I tumors accounted for 58.33% followed by grade II tumors with an average of 22.91% with the least common being grade IV tumors accounting for 8.33%. The grade distribution is depicted in Figure 6.

Table 1

Distribution of histological subtypes (number and percentage)

Histological diagnosis	Number of cases	Percentage(%)	WHO grade
Pilocytic astrocytoma	6	11.53	I
Pilomyxoid astrocytoma	1	1.92
Diffuse astrocytoma	1	1.92	II
Anaplastic oligodendroglioma	2	3.84	III
Small cell glioblastoma	1	1.92	IV
PXA	3	5.76	II
SEGA	1	1.92	I
DNET	2	3.84	I
Ganglioglioma	1	1.92	I
ATRT	1	1.92	IV
PNET/Ewing’s sarcoma	2	3.84
Craniopharyngioma	13	25	I
Meningioma	3	5.76	I
Atypical meningioma	2	3.84	II
Ependymoma	5	9.62	II
Anaplastic ependymoma	3	5.76	III
Pituitary macroadenoma	2	3.84
Pineoblastoma	1	1.92	IV
Atypical choroid plexus papilloma	1	1.92	II
Choroid plexus carcinoma	1	1.92	III

PXA = pleomorphic xanthoastrocytoma, SEGA = subependymal giant cell astrocytoma, DNET = dysembryoplastic neuroepithelial tumor, ATRT = atypical teratoid/rhabdoid tumor

Figure 5

Distribution of astrocytic, oligodendroglial, and glioneuronal tumors

Figure 6

Distribution of WHO grading of supratentorial tumors

There were 13 cases of craniopharyngiomas with the most common subtype being the adamantinomatous type. Of the 13 cases of meningiomas, two were meningothelial meningiomas, one transitional, and two atypical meningiomas. We had eight cases of ependymomas, of which three are anaplastic ependymomas, one papillary and one tanycytic ependymoma [Figures 5 and 6].

DISCUSSION

Pediatric neurooncology is evolving as a highly challenging and specialized field and in view of increasing incidence of childhood brain tumors and high rates of mortality in children,[1] it demands a comprehensive multidisciplinary approach.[2] However, in India there are very few population-based studies concerning the incidence and histomorphological profile of pediatric supratentorial tumors.[3]

Demography

In our study, the overall incidence of pediatric CNS tumors was found to be 10.31% which is slightly higher compared with CBTRUS statistics (6.06%)[19] but is in parallel with NIMHANS and CMC Vellore statistical data.[3] Among the pediatric brain tumors, supratentorial tumors constituted 44.44% with 52 cases and infratentorial tumors accounting for 55.55% (65 cases) which correlates with the study conducted by Govindan[4] and Sánchez et al.[5] Supratentorial tumors usually show a less dramatic clinical presentation compared to infratentorial tumors[6] and the most common clinical features being headache and vomiting.[2]

Among the supratentorial tumors, extraaxial tumors predominated with 51.98% which is attributed to the greater proportion of craniopharyngiomas (25%)[26] and extraaxial location of six cases of pilocytic astrocytomas (11.53%).

There is a slight male preponderance with a male: female ratio of 1.7:1 which is comparable to the study by Shirazi et al.[7] and Rickert et al.[8] Incidence of pediatric supratentorial tumors is most common in the age group of (13–18) years which is comparable to a study in North Kerala, India.[4]

Histopathology

In this study, the most frequent pediatric supratentorial tumors in descending order are astrocytomas and craniopharyngioma followed by ependymoma. WHO Grade I/II tumors comprising 81% were more common compared with Grade III/IV tumors(19%) and shows concordance with a study conducted by El-Gaidi et al.[9] implying the incidence of low-grade tumors are more common in supratentorial location while tumors in the infratentorial compartment are mostly high-grade tumors and show a more aggressive behavior.

Astrocytic tumors

Astrocytomas accounted for 26.92% and constituted the most common supratentorial pediatric CNS tumor which is comparable to the studies in India[123] and International studies.[10111210-13]

Pilocytic astrocytoma comprised the single most frequent astrocytic tumor (WHO grade I) with 6 cases constituting 40% of pediatric gliomas and 11.53% of supratentorial CNS tumors, which is consistent with CBTRUS statistical data[19] and other published studies.[26,1214] All the six cases had a supratentorial extraaxial location with four cases arising from Optic nerve and two with chiasmatic/hypothalamic location. One of the lesion radiologically mimicked craniopharyngioma similar to a study by Skipworth et al.[20] We also reported a case of extraaxial pilocytic astrocytoma presenting with recurrence. The patient complained of headache and loss of vision in the right eye 4 months postsurgery. Recurrence in pilocytic astrocytoma is uncommon and is attributable to various factors.[21]Table 2 shows the comparative analysis of current study with other studies.

Table 2

Comparative analysis of this study with national and international studies

Histological diagnosis	This study (%)	Jain et al.,[3] India (%)	Zhou et al.,[10] Beijing (%)	El-Gaidi,[9] Egypt (%)
Astrocytoma	26.92	34.7	30.5	35
Craniopharyngioma	25	10.2	18.4	11.3
Ependymoma	15.38	9.8	5.6	10.4

We reported one case of small cell glioblastoma in a 16-year-old male patient presenting with a space-occupying lesion in the left temporal region representing 1.92% of supratentorial tumors. Glioblastoma is a WHO Grade IV tumor which is rare in children and most commonly involve frontal and temporal lobes. Small cell variant of glioblastoma is associated with dismal prognosis in children.[22]Figure 7 shows the histological spectrum of glial tumours.

Figure 7

(A) Pilocytic astrocytoma. (B) Pilocytic astrocytoma (40X). (C) Small cell glioblastoma (4X). (D) Small cell glioblastoma (40X). (E) PXA. (F) PXA (40X). (G) SEGA. (H) Anaplastic Oligodendroglioma (4X). (I) Anaplastic Oligodendroglioma (40X)

Interestingly, in our study craniopharyngiomas were the second most common supratentorial neoplasm constituting 25% with a predominant extraaxial suprasellar location, although the overall incidence of pediatric craniopharyngiomas was 1.14% which is well in concordance with international statistics.[19] Various studies conducted in India[34,18] as well as International studies conducted in Egypt, China, Brazil, Korea, and Japan[910,1315,16] showed similar results. These results, however, contradicted with the results of certain international studies,[812,23] which showed an increased frequency of ependymomas compared to craniopharyngiomas. Table 3 shows comparative analysis of pedriatric CNS gliomas with other studies.

Table 3

Comparison of percentage distribution of pediatric CNS gliomas with other studies

Histological subtype (WHO grade)	Present study (%)	Multi-institutional study (India)[3] (%)
Grade I (pilocytic astrocytoma + SEGA)	13.45	23.1
Grade II (PXA + diffuse astrocytoma)	7.68	5.1
Grade III astrocytoma	–	2.1
Grade IV astrocytoma	1.92	4.4
Anaplastic oligodendroglioma grade III	3.84	0.4

Ependymomas are the third most common tumors reported in our group with 15.38% which is comparable to various studies.[37,1317] Among the ependymomas, WHO grade II tumors constituted 9.62% and anaplastic grade III ependymomas accounted for 5.76%. Meningiomas were the next common neoplasms encountered with an incidence of 9.6%. The histological profile of craniopharygioma, ependymoma and meningioma in Figure 8.

Figure 8

(A) Craniopharygioma. (B) Craniopharyngioma. (C) Transitional meningioma. (D) Atypical meningioma. (E) Papillary ependymoma. (F) Tanycytic ependymoma. (G) Anaplastic ependymoma. (H) Pituitary adenoma

Choroid plexus tumors accounted for 3.84% of supratentorial tumors with one reported case of atypical choroid plexus papilloma and other cases of choroid plexus carcinoma, both arising in the lateral ventricle in children <2 years of age. The incidence was found to be consistent with a study conducted by Govindan et al.,[4] in India and also with studies in other countries.[915,25] Choroid plexus papilloma and carcinomas are more common in the lateral ventricular region with the incidence more common in children younger than 2 years of age.[24]

Other less commonly reported entities were Pilomyxoid astrocytoma, SEGA, Ganglioglioma, DNET, atypical teratoid/rhabdoid tumor, pituitary adenoma, pineoblastoma.

On follow-up, children with WHO grade I/II tumors and tumors amenable to complete surgical resection had better survival and improved quality of life in contrast to increased mortality in patients with high-grade tumors and tumors with craniospinal seeding.

This is a single institution based study wherein we have attempted to profile the incidence and highlight the diverse histological spectrum of pediatric supratentorial tumors.

CONCLUSION

From our study, we observed that the supratentorial pediatric tumors tend to have a less dramatic and an insidious clinical course and heterogenous histomorphological features. With respect to topography, extraaxial suprasellar tumors predominated with a comparative increase in the incidence of craniopharyngiomas. Improved survival in supratentorial tumors is attributable to the anatomical location and a relatively high incidence of low-grade tumors in the supratentorial location. To date, pediatric supratentorial tumors show a steady rise in incidence as evidenced by various national and international studies and mandate an updated epidemiological database and surveillance and incorporation of molecular testing for formulating and implementing management protocols and strategies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.