Childhood Tumors of the Brain: Demographic Pattern ...

Original Paper Received: November 3, 2010 Accepted after revision: March 8, 2011 Published online: May 5, 2011

Pediatr Neurosurg 2011;47:31–37 DOI: 10.1159/000327143

Childhood Tumors of the Brain: Demographic Pattern over a Ten-Year Period in the Kashmir Valley Khursheed Nayil a Rumana Makhdoomi b Altaf Ramzan a Sheikh Zahoor a Mohsin Rasool b Abrar Wani a Anil Dhar a Basharat Mubeen b Sarbjit Singh a Rashid Bhat a Altaf Kirmani a

Departments of a Neurosurgery and b Pathology, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India

Key Words Brain tumor ⴢ Astrocytoma ⴢ Kashmir Valley ⴢ Demographic pattern

ryngioma and medulloblastoma, respectively. Our experience reflects a different demographic profile of pediatric brain tumors as compared with other regions of the world. Copyright © 2011 S. Karger AG, Basel

Abstract Brain tumors in children represent the second most frequent tumors in this age group after hematologic malignancies. We highlight the demographic pattern after retrospective analysis of brain tumors in children from geographically and ethnically distinct Kashmir Valley managed in our center between 2000 and 2009. We had a total of 248 pediatric patients with brain tumors. The parameters analyzed were age, gender, location of tumors and histopathological subtypes as well as WHO grade of tumor. We also did a comparison between the frequencies of common varieties of tumor in the first and second 5-year periods. We found that 111 tumors (44.75%) were supratentorial, and 137 (55.25%) were infratentorial. The male-to-female ratio was 1.4:1. The proportions of low-grade and high-grade tumors were 60 and 40%, respectively. The most common tumor in our series was astrocytoma. The most common tumors in the supratentorial and infratentorial compartments were craniopha-

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Introduction

Tumors of the brain in children are the second most common malignancy in the pediatric age group and the most common solid tumors in children [1]. There are several studies on the epidemiology and distribution of brain tumors from Asia [2, 3], Europe [4], Africa [5] and North America [6, 7] which show different patterns in different regions. No such study is available from India; thus we analyzed brain tumors in pediatric age in the Kashmir Valley, which is a geographically distinct zone stretching over a 200 ! 200 mile area in the Himalayan Mountains, and the incidence of various tumors is different from that in the rest of India [8, 9]. We endeavored to analyze the demographic parameters, site distribution of brain tumors, histopathological types and grades over the last 10 years.

Dr. Khursheed Nayil Department of Neurosurgery Sher-i-Kashmir Institute of Medical Sciences Srinagar 190011 (India) Tel. +91 94 1999 9465, E-Mail nayilkhursh @ gmail.com

Patients and Methods This is a retrospective study conducted in the Departments of Neurosurgery and Pathology at the Sher-i-Kashmir Institute of Medical Sciences, Kashmir, India. This institute caters to the entire population of the Kashmir Valley. The study period was from 2000 to 2009, a period of 10 years. The study period was divided into two halves, i.e. from 2000 to 2004 and from 2005 to 2009. This was done to observe any change in the pattern of any tumor. All the children aged ^18 years who were admitted with a diagnosis of brain tumor were included in this study. The parameters analyzed were age, gender, location of the tumor on CT/MRI, histopathological type, and grade of the tumor according to the WHO 2007 classification [10]. The age groups of the patients were stratified as 0–2 years, 12–5 years, 15–10 years, 110–15 years and 115– 18 years. Biopsy of the tumors was obtained mostly after open surgery or sometimes stereotactically. All the biopsy specimens were reexamined and redefined by a single pathologist. Routine hematoxylin-eosin was used for staining the biopsy specimens. However, at times special stains, namely phosphotungstic acid hematoxylin and immunohistochemistry, were used in a few cases.

Results

There were 145 boys and 103 girls with brain tumors in the study. The male-to-female ratio was 1.4:1. Supratentorial tumors were seen in 111/248 patients (44.75%) and infratentorial tumors in 137/248 patients (55.25%; table 1). The age group most frequently involved was the 110- to 15-year group. In the age group of 0–2 years, only high- grade tumors were seen which included 8 glioblastomas multiforme, 4 supratentorial primitive neuroectodermal tumors (PNET) and 4 malignant ependymomas. Astrocytoma and craniopharyngioma were most common in the 110- to 15-year age group, medulloblastoma in the 15- to 10-year group, and ependymomas in the 12to 5-year group (table 2; fig. 1). Overall, the most common tumor in our series of 248 patients was astrocytoma (29%; table 3). In the supratentorial compartment, the most common tumor was craniopharyngioma (20%), whereas in the infratentorial compartment, the most common tumor was medulloblastoma (21%; table 1). There were 18 brain stem astrocytomas (7.25%), with a ratio of 2.6:1 (13 of high grade and 5 of low grade) between the high- and low-grade subtypes. Overall, we had 149/248 (60%) low-grade tumors (WHO grades I/II) and 99/248 (40%) high-grade tumors (WHO grades III/IV; table 4). In the low-grade tumor group, the male-to-female ratio was 1.06:1 (77 boys and 72 girls), and in the high-grade tumor group, it was 2.19:1 (68 boys and 31 girls; p = 0.009), a difference which was statistically significant. 32

Pediatr Neurosurg 2011;47:31–37

Table 1. Compartments involved by tumors (n)

Supratentorial Infratentorial (n = 111) (n = 137) Astrocytoma 20 Medulloblastoma 0 Craniopharyngioma 50 Ependymoma 0 Choroid plexus papilloma 5 Germ cell tumor 5 Oligoastrocytoma 5 Meningioma 4 Pituitary adenoma 4 Supratentorial PNET 4 Ganglioglioma 3 Oligodendroglioma 3 Hemangioblastoma 0 Central neurocytoma 2 DNET 2 Epidermoid 0 Schwannoma 1 Choroid plexus carcinoma 1 Extraventricular neurocytoma 0 Astroblastoma 1 Pleomorphic xanthoastrocytoma 1

52 53 0 26 0 0 0 0 0 0 0 0 2 0 0 2 1 0 1 0 0

DNET = Dysembryoplastic neuroepithelial tumor.

A few other tumors observed by us were: germ cell tumors of the posterior third ventricle (4 cases) and suprasellar area (1 case), 4 meningiomas, 4 pituitary tumors, 6 choroid plexus tumors, 1 facial nerve schwannoma, 1 extraventricular neurocytoma [11] and 1 frontal intraparenchymal schwannoma [12]. There were no lymphomas or metastases in our series. The craniopharyngiomas were of the adamantinomatous type, and all the pituitary tumors were nonfunctioning. When comparing our series with other studies from the Far East (China) [3], Middle East (Syria) [2], Africa (Tunisia) [5], Europe (Germany) [4], North America (USA [6] and Canada [7]), we observed that astrocytomas were the most common tumors in most of the series, except in a series from Syria in which medulloblastoma was the most common tumor reported (table 5; fig. 2). We also compared our data from the first 5-year period (2000– 2004) with the second 5-year period of our series (2005– 2009), and we observed that the percentage of ependymomas had almost doubled (6.17 vs. 12.57%; p ! 0.05; fig. 3). Some rarer varieties of tumors, i.e. ganglioglioma, dysembryoplastic neuroepithelial tumor, pleomorphic xanthoastrocytoma, extraventricular neurocytoNayil et al.

n 25 20 15 10 5 0

As

Fig. 1. Age-related frequencies of a few common brain tumors.

0–2 years >2–5 years >5–10 years >10–15 years >15–18 years

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ma, intraparenchymal schwannoma and facial nerve schwannoma were observed in the second 5-year period as well (table 3). There were no familial cases in our study.

Discussion

The incidence of brain tumors varies from region to region and between ethnic groups – the Kashmiri population being one of the ethnic groups of Asia – and some of the tumors such as carcinoma of the stomach, esophagus and skin (Kangri cancer) have a high prevalence in the valley probably secondary to dietary (stomach and esophagus), cultural and environmental factors (Kangri cancer) [8, 9]. However, a study by Rumana et al. [13] on the clinicopathologic characteristics of brain gliomas over a period of 3 years in the Kashmir Valley found no deviation in the pattern of gliomas from that in the rest of India. The incidence of childhood brain tumors varies from region to region and depends upon ethnicity as well. Some variation in incidence is due to varying definitions of upper limits of the age of childhood, which varies between 14 and 17 years [2–7]. Another factor could be the lack of proper investigations in underdeveloped countries, thus yielding a fake low incidence, as has been observed in a few studies [14, 15]. The median age at diagnosis varies from series to series, with the age group of 5–10 years as the most common one involved [5, 16, 17]. In our study, we observed that the 110- to 15-year age group was most frequently involved. Males have consistently been reported to be affected more often than females, and this holds true for both childhood and adult brain tumors [2, 5, 18–20]. However, a series from Africa reports a female preponderance regarding childhood brain tumors [21]. The Childhood Brain Tumors in the Kashmir Valley

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Table 2. Age-related frequencies of common types of brain tumor 0–2 years

Astrocytoma Medulloblastoma Craniopharyngioma Ependymoma Germ cell tumor Supratentorial PNET Total

>2–5 years

>5–10 >10–15 >15–18 Total years years years

8 0 0 4 0 4

14 9 8 12 0 0

13 21 11 9 3 0

25 18 22 1 2 0

12 5 9 0 0 0

72 53 50 26 5 4

16

43

57

67

26

210

Values in italics are the most common tumors in the corresponding age groups.

male-to-female ratio in our series was 1.4:1, and males outnumbered females in all tumor types and all age groups. The male predominance was most striking for high-grade tumors, for which the male-to-female ratio was 2.19:1, as compared with the male-to-female ratio for low-grade tumors, which was 1.06:1, and the difference was found to be statistically significant (p = 0.009). In an earlier 3-year study from our institute on gliomas of the brain, the male-to-female ratio for high-grade gliomas was 2.8:1, as compared with low-grade gliomas, for which it was 1.94:1. Most of the patients in our series [13] had infratentorial tumors. This was because of the higher frequency of medulloblastomas in our series. Kadri et al. [2] from Syria found in their series that infratentorial tumors outnumbered supratentorial tumors. Similarly, Yates et al. [7] from Canada in their series observed infratentorial tumors more often than supratentorial tumors. However, a series on childhood brain tumors from Tunisia [5] rePediatr Neurosurg 2011;47:31–37

33

Table 3. Frequency of brain tumors in our study

Table 4. Frequency of low-grade and high-grade tumors

2000–2004 2005–2009 Total (n = 81) (n = 167) (n = 248) Astrocytoma Grade I Grade II Grade III Grade IV Medulloblastoma Craniopharyngioma Ependymoma Choroid plexus papilloma Germ cell tumor Oligoastrocytoma Meningioma Pituitary adenoma Supratentorial PNET Ganglioglioma Oligodendroglioma Hemangioblastoma DNET Central neurocytoma Epidermoid Schwannoma Choroid plexus carcinoma Extraventricular neurocytoma Astroblastoma Pleomorphic xanthoastrocytoma

24 (29.62) 12 (50) 7 (29) 3 (12.5) 2 (8.5) 19 (23.45) 14 (17.28) 5 (6.17) 2 4 2 2 1 3 0 1 1 0 1 1 0 1

48 (28.74) 18 (37.5) 18 (37.5) 9 (18.7) 3 (6.3) 34 (20.35) 36 (21.55) 21 (12.57) 3 1 3 2 3 1 3 2 1 2 1 1 2 0

72 (29) 30 (41.7) 25 (34.8) 12 (16.6) 5 (6.9) 53 (21) 50 (20) 26 (10) 5 5 5 4 4 4 3 3 2 2 2 2 2 1

0 0

1 1

1 1

0

1

1

Figures in parentheses are percentages. DNET = Dysembryoplastic neuroepithelial tumor.

ported 50.24% tumors in the supratentorial, and 49.76% in the infratentorial compartment. In a series of 1,371 brain tumors in children, Zhou et al. [3] from China found a supratentorial location more often. This was because in their series, the incidence of astrocytoma was much higher than in our series. Though astrocytoma was the most common tumor in our series, even then infratentorial tumors outnumbered supratentorial tumors because there were 52 astrocytomas of the brain stem and cerebellum. In our study, astrocytoma was the most frequent tumor followed by medulloblastoma. Similar results have been reported in studies from Tunisia [5], UK [22], Iran [23], the USA [6] and Canada [7]. We had a predominance of low-grade tumors (60 vs. 40%) similar to values which have been reported from Syria [2], China [3], Tunisia [5] and Canada [7], i.e. 67.3, 53.5, 65 and 40.9%, respectively. 34


Astrocytoma Medulloblastoma Craniopharyngioma Ependymoma Choroid plexus papilloma Germ cell tumor Oligoastrocytoma Meningioma Pituitary adenoma Supratentorial PNET Ganglioglioma Oligodendroglioma Hemangioblastoma Central neurocytoma DNET Epidermoid Schwannoma Choroid plexus carcinoma Extraventricular neurocytoma Astroblastoma Pleomorphic xanthoastrocytoma

Low-grade tumors (n = 149; 60%)

High-grade tumors (n = 99; 40%)

55 0 50 11 5 0 4 4 4 0 2 2 2 2 2 2 2 0 1 0 1

17 53 0 15 0 5 1 0 0 4 1 1 0 0 0 0 0 1 0 1 0

DNET = Dysembryoplastic neuroepithelial tumor.

We noticed 41.7, 34.8, 16.6 and 6.9%, respectively, of WHO grade I, II, III and IV astrocytomas (table 3). Medulloblastoma cases comprised 21% of our patients. The peak age group was 15–10 years. Medulloblastoma was the most common tumor in a series of 367 total tumors reported from Syria [2], followed by astrocytomas (25.8%). The peak age group in their series for medulloblastoma was 6–8 years. In another large series of 1,371 pediatric brain tumors from China [3], medulloblastoma was the third most frequent tumor (14.6%) after astrocytoma (30.5%) and craniopharyngioma (18.4%). In a Canadian series of 689 pediatric brain tumors, medulloblastoma was the second most common brain tumor after astrocytoma. It accounted for 16.3% of the total brain tumors (table 5). Craniopharyngiomas have a bimodal distribution for age at presentation. The first peak is at 5–15 years and another peak in adult life [24]. In children, most of the tumors are of adamantinomatous subtypes. Craniopharyngiomas were seen in 20% of our patients, and the age group most affected was 110–15 years. In a neighboring country like China, craniopharyngioma comprised Nayil et al.

n 50 45 40 35 30 25 20 15 10 5 0

Fig. 2. Comparative analysis of brain tumor frequencies from the Near East (China), Middle East (Syria), Africa (Tunisia), Europe (Germany), North America (Canada) and the Kashmir Valley.

Astrocytoma Medulloblastoma Craniopharyngioma Ependymoma Germ cell tumor

Ch

in

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Sy

ria

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isi

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n 30 25 20 15 10 5 0 Astrocytoma

Medulloblastoma

Craniopharyngioma

Fig. 3. Pattern of common tumors over the

2000–2004

29.62%

23.45%

17.28%

Ependymoma* 6.17%

last decade. The incidence of ependymoma has increased significantly. * Statistically significant at p ! 0.05.

2005–2009

28.74%

20.35%

21.55%

12.57%

Table 5. Comparison of common tumors between various regions in percentages

Astrocytoma Medulloblastoma Craniopharyngioma Ependymoma Germ cell tumor

Syria [2]

China [3]

Germany [4]

Tunisia [5]

Canada [7]

Present study

25.8 27.5 14.1 11.4 1.1

30.5 14.6 18.4 5.6 7.9

47.3 16.3 5.6 10.1 2.5

38 16.2 6.3 6.9 2.5

40.9 16.3 6.0 12.8 2.3

29 21 20 10 2

Values in italics are the most common tumors in the respective series.

Childhood Brain Tumors in the Kashmir Valley


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18.38% of brain tumors in children [3]. Similarly, a high percentage of craniopharyngiomas (14.1%) was reported from Syria by Kadri et al. [2]. However, contrastingly, a low incidence of 6.3% was reported from Tunisia [5], 6.6% from Canada [7] and 4.4% from Germany [4]. In the USA, the overall incidence of craniopharyngioma is also low, with 96 craniopharyngiomas occurring per year in children [25]. So far, our study has reported the highest incidence of pediatric craniopharyngioma (table 5). It remains to be seen if it is related to genetic or to any environmental carcinogen; further studies in this regard need to be done. Ependymomas are malignant tumors and occur mostly below 5 years of age. Their overall incidence is increasing [26]. Studies from other Asian countries, e.g. China [3], and Saudi Arabia [27] show low incidence rates of ependymomas, i.e. 5.64 and 3.5%, respectively. However, reports from Canada [7], Syria [2], Mexico [16] and Germany [18] quote high frequencies, i.e. 12.8, 11.4, 11 and 10%, respectively. Ependymomas comprised 10% of the tumors in our series, 6.17% in the first 5-year period and 12.57% in the second half. The difference was statistically significant at p ! 0.05. We also compared the patterns for other common tumors such as astrocytoma, medulloblastoma and craniopharyngioma between the first and second 5-year periods, but we did not notice any sta-

tistically significant change in the frequencies of these tumors (fig. 3). Germ cell tumors usually arise from the posterior third ventricular region and sometimes can arise from the suprasellar area. These tumors are common in Japan (13.25%) [20], Korea (11.2%) [28] and China (7.9%) [3]. Despite being in the neighborhood of China, we observed only 5 germ cell tumors (2%) in the entire 10-year period. Out of these 5 tumors, 4 were observed in the first 5-year period arising from the posterior third ventricular area, and 1 was seen in the suprasellar area in the second 5-year period. Our observation supports the fact that the Kashmir Valley falls in the low-risk area for pediatric germ cell tumors of the brain. Reports from Syria [2], Canada [7] and Germany [18] also suggest a low incidence of these tumors, proving that certain brain tumors have a racial association. Our analysis of 248 patients of childhood brain tumors suggests that the profile of childhood brain tumors in the Kashmir Valley differs from what has been reported in the literature, and even from that of neighboring countries like China. In conclusion, the demographic and histopathological diversities noticed in studies from different parts of the world reflect that environmental, ethnic as well as genetic factors all contribute to the development of brain tumors in children.

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