Primary pediatric brain tumors

Primary Pediatric Brain TumorsStatistics of Taipei VGH, Taiwan (1975–2004)

Tai-Tong Wong, M.D.1

Donald M. Ho, M.D.2

Kai-Ping Chang, M.D.3

Sang-Hue Yen, M.D.4

Wan-You Guo, M.D., Ph.D.5

Feng-Chi Chang, M.D.5

Muh-Lii Liang, M.D.1

Hung-Chi Pan, M.D.1

Wen-Yuh Chung, M.D.1

1 Department of Neurosurgery, Neurological Insti-tute, Taipei Veterans General Hospital and NationalYang Ming University, School of Medicine, Taiwan,Republic of China.

2 Department of Pathology and Laboratory Medi-cine, Taipei Veterans General Hospital and NationalYang Ming University, School of Medicine, Taiwan,Republic of China.

3 Department of Pediatrics, Taipei Veterans Gen-eral Hospital and National Yang Ming University,School of Medicine, Taiwan, Republic of China.

4 Cancer Center, Taipei Veterans General Hospitaland National Yang Ming University, School of Med-icine, Taiwan, Republic of China.

5 Department of Radiology, Taipei Veterans Gen-eral Hospital and National Yang Ming University,School of Medicine, Taiwan, Republic of China.

Supported by the Pediatric Neuroscience ResearchFund of Taipei Veterans General Hospital, Taipei,Taiwan, Republic of China.

Address for reprints: Tai-Tong Wong M.D., Divisionof Pediatric Neurosurgery, Neurological Institute,Taipei Veterans General Hospital, VACRS, No. 210,Sec 2, Shih-Pai, Taipei, Taiwan, Republic of China,11217; Fax: (011) 886-2-28757587; E-mail:[email protected]

Received February 9, 2005; revision received April29, 2005; accepted June 3, 2005.

BACKGROUND. The purpose of the current study was to investigate a hospital series

of 986 cases of primary pediatric brain tumors in Taiwan.

METHODS. The authors reviewed the database of primary pediatric brain tumors in

patients � 18 years of age collected in Taipei Veterans General Hospital (Taipei

VGH) from 1975 to May 2004. Age and gender distribution, location, and classifi-

cation of brain tumors were analyzed. Intracranial tumors with diagnostic imaging

were included. Nontumoral lesions, cysts, and vascular malformations were ex-

cluded.

RESULTS. The mean age of these 986 patients was 7.8 years, and the male to female

ratio was 1.4:1. Supratentorial (including pineal– quadrigeminal) located tumors

(58.3%) was predominant to infratentorial tumors (41.1%). In these series, 886

patients had either histologic diagnosis (842 patients) or clinical diagnosis (44

patients). The most common 5 categories of tumors were astrocytic tumors

(31.1%), germ cell tumors (14.0%), medulloblastomas (13.3%), craniopharyngio-

mas (8.3%), and ependymal tumors (5.8%). Atypical teratoid/rhabdoid tumors

(AT/RTs), a rare but highly malignant tumor, were 2.1%. The high incidence of

primary intracranial germ cell tumors correlated with reported series from Japan

and Korea. For the remaining 100 patients without diagnostic classifications, the

majority were most likely astrocytic tumors in brain stem.

CONCLUSIONS. The authors analyzed a large hospital series of primary brain tumors

in children. Both histologically verified and unverified tumors were recruited to

avoid selective bias. Although it was not a study of a population-based brain tumor

registry, it could still be representative of primary pediatric brain tumors in Tai-

wan. Cancer 2005;104:2156 – 67. © 2005 American Cancer Society.

KEYWORDS: brain tumor, childhood, demographic data, Taiwan.

In Taiwan, the earliest reported series of pediatric brain tumor was126 cases at the National Defense Medical Center (NDMC) in 1977

and 87 cases at the National Taiwan University Hospital (NTUH) in1980.1,2 Taipei VGH later reported a series of 171 CT scan detectedchildhood brain tumors in 1987.3 Since then, large series of pediatricbrain tumors has not been studied. From 1975 to May 2004, wecollected 986 cases of primary brain tumors in children younger than18 years of age in Taipei VGH. Demographic data (age distribution,gender ratio, location, and classification of tumors) of these patientswere reviewed and analyzed. We were interested in classifying eitherhistologically or clinically the tumors that were detected by neuroim-aging studies.

MATERIALS AND METHODSIn this study, we reviewed the database of 986 cases of primarypediatric brain tumors of younger than 18 years of age collected inTaipei VGH from 1975 to May 2004. Primary intracranial tumors that

2156

© 2005 American Cancer SocietyDOI 10.1002/cncr.21430Published online 11 October 2005 in Wiley InterScience (www.interscience.wiley.com).

were diagnosed by CT scan or MRI were included.Nontumoral lesions, cysts, and vascular malforma-tions were excluded. Among them, 849 (86.1%) pa-tients received surgeries for tumors, and 842 (85.4%)had histologic diagnosis. Of the 144 patients withouthistologic diagnosis, 44 had clinical diagnosis. Eighty-four patients were referred after initial tumor surgeriesin other hospitals, and 46 of them received furthertumor surgeries at Taipei VGH for residue or recurrenttumors. Twenty-six patients died within 1 month aftertumor surgeries with a surgical mortality rate of 3.2%.Demographic data (age, gender, location, and classi-fication of tumors) of these patients were analyzed.The distribution of tumors was defined by imagingstudies and/or operative findings. Tumor locationswere counted as supratentorial, infratentorial, bothsupratentorial and infratentorial, and also their re-lated neuroanatomic locations. Tumors with histo-logic diagnosis were classified according to the WorldHeath Organization 2000 classification as closely aspossible.4 For tumors that were operated upon in Tai-pei VGH, the histologic diagnosis was reviewed andreconfirmed by one senior neuropathologist. For tu-mors without tissue proof, the diagnoses and classifi-cations were made from related specific clinical fea-tures, image findings, and locations of tumors. Forgerm cell tumors (GCTs) without histologic verifica-tion, the diagnosis and classification were achievedthrough image findings, locations, tumor markers andresponse to radiotherapy and/or chemotherapy. Braintumors of phacomatoses without surgical resectionwere classified according to specific locations, andentities of central nervous system (CNS) tumors oc-curred in different syndromes. For hypothalamichamartomas, the classification could be made simplythrough magnetic resonance imaging (MRI) findings.We were also interested in studying data of severalspecific entities: GCTs, atypical teratoid/rhabdoid tu-mors (AT/RTs), phacomatoses, and radiation-inducedsecond tumors.

RESULTSAge Distribution and Gender RatioOf these 986 patients, the mean age was 7.8 years(range from the first day of life to 18 yrs) with peakfrequency at 2, 6, 10, and 13 years. The tumors werediagnosed within 1-year-olds in 61 (6.2%) patients.There were 579 (58.7%) boys and 407 (41.3%) girls,with male to female ratio of 1.4:1. Except the agegroups of 2 and 8 years, there was male predominancein all other age groups (Fig.1, Table 1).

Age distribution of different types of tumorsAccording to the mean age at diagnosis, immatureteratomas in ventricles (2.1 yrs), choroids plexus tu-

mors (2.2 yrs), supratentorial primitive neuroectoder-mal tumors (PNET) (3.5 yrs), AT/RTs (4.2 yrs), pine-oblastomas (4.8 yrs), and ependymal tumors (6.0 yrs)occurred in younger age groups. Medulloblastomas(7.0 yrs), astrocytic tumors (7.5 yrs), craniopharyngio-mas (7.8 yrs), and oligodendroglioma (7.9 yrs) werecommon tumors in children 7– 8 years old. Neuronaland mixed neuronal glial tumors (8.6 yrs), germ celltumors (10.6 yrs), tumor of meninges (10.7 yrs), andpituitary tumors (14.3 yrs) were usually diagnosed inolder children. The age distribution and gender ratioof different types of tumors are listed in Tables 2–3.

Gender ratio (male to female ratio) of different types oftumorsOf the five most common types of tumors in children,the gender ratios of astrocytic tumors, ependymal tu-mors, craniopharyngiomas, medulloblastomas, andgerm cell tumors were 1.0, 1.4, 1.5, 1.9, and 3.8, re-spectively. Except astrocytic tumors, all other fourtypes of tumors were predominantly in males. Thistendency of male predominance (above the averageratio of 1.4) was clear in medulloblastoma and germcell tumors. For germ cell tumors, only yolk sac tu-mors or tumors in the suprasellar region were equal ingender ratio or female predominant (Tables 2–3).

FIGURE 1. Chart graphically depicts the age distribution of 986 patients.

TABLE 1Age and Sex Distribution of Pediatric Brain Tumors (N � 986)

Age yrs

Male Female Total

No. % No. % No. %

0–1 36 3.7 25 2.5 61 6.20–2 68 6.9 69 7.0 137 13.90–5 173 17.5 133 13.5 306 31.06–10 197 20.0 148 15.0 345 35.011–15 177 18.0 107 10.8 284 28.816–18 32 3.2 19 1.9 51 5.2Total 579 58.7 407 41.3 986 100

Average age: 7.8 yrs Male to female ratio: 1.4

Primary Pediatric Brain Tumors/Wong et al. 2157

TABLE 2Classification and Age and Gender Distributions of Primary Pediatric Brain Tumors in Taipei VGH

Types of tumorsNo. ofpatients

Cases ofhistologydiagnosis

Cases ofclinicaldiagnosis Mean age (range)

Genderratio(M/F)

Percentagehistologicdiagnosis

PercentageN � 986

Gliomas 403 401 2 7.0 yrs (3 days–17.8 yrs) 1.1 99.5 40.9Astrocytic tumors 307 305 2 7.5 yrs (3 days–17.8 yrs) 1.0 99.3 31.1

Pilocytic astrocytoma 131 131 0 7.0 yrs (4.4 mos–16.4 yrs) 1.0 100 13.3Astrocytoma 74 74 0 7.5 yrs (4.4 mos–15.7 yrs) 1.0 100 7.5Anaplastic astrocytoma 45 45 0 8.6 yrs (3 days–16.6 yrs) 1.3 100 4.6Glioblastoma 39 39 0 7.0 yrs (2.8 mos–17.8 yrs) 0.7 100 4.0Giant cell astrocytoma 13 11 2 8.0 yrs (1–11.6 yrs) 3.3 84.6 1.3PXAa 4 4 0 7.8 yrs (7.9 mos–13 yrs) 4/0 100 0.4Primary leptomeningeal gliomatosis 1 1 0 12.5 yrs 0/1 100 0.1

Oligodendroglial tumors 12 12 0 7.9 yrs (1.1 mos–15.1 yrs) 1.4 100 1.2Ependymal tumors 56 56 0 6.0 yrs (3.8–17.4 mos) 1.3 100 5.7

Ependymoma 25 25 0 5.8 yrs (10.1 mos–16.8 yrs) 1.3 2.5Anaplastic ependymoma 31 31 0 6.0 yrs (3.8 mos–17.4 yrs) 1.4 3.1

Choroid plexus tumors 19 19 0 2.2 yrs (0.5 mos–12.4 yrs) 1.4 100 1.9Choroid plexus papilloma 17 17 0 2.4 yrs (0.5 mos–12.4 yrs) 1.1 1.7Choroid plexus carcinoma 2 2 0 1.2 yrs (9.0 mos–1.6 yrs) 2/0 0.2

Glial tumor of uncertain origin 1 1 0 9.0 yrs 0/1 100 0.1Astroblastoma —

Mixed gliomas 7 7 0 6.1 yrs (5.6 mos–12.7 yrs) 2.5 100 0.7Embryonal tumors 165 165 0 6.4 yrs (1 day–18 yrs) 1.7 100 16.7

Medulloblastomas 131 131 0 7.0 yrs (2.5 mos–18 yrs) 1.9 100 13.2PNET/supratentorial 12 12 0 3.5 yrs (1 day–13 yrs) 0.7 100 1.2Ependymoblastoma 1 1 0 1.7 yrs 1/0 100 0.1AT/RTs 21 21 0 4.2 yrs (0.5 mos–10.7 yrs) 1.6 100 2.1

Germ cell tumors 138 105 33 10.6 yrs (3 days–18 yrs) 3.8 75.5 14.0Germinoma 75 52 23 11.9 yrs (1.3–18 yrs) 4.0 69.3 7.6Teratoma, mature 8 8 0 6.9 yrs (8.5 mos–15.3 yrs) 8/0 100 0.8Teratoma, immature 14 14 0 6.8 yrs (7 days–14.4 yrs) 13 100 1.4YST, pure 10 10 0 10.0 yrs (2.6–14.5 yrs) 1.0 100 1.0Mixed GCTsb 19 19 0 10.1 yrs (1.6–15.4 yrs) 2.8 100 1.9

G � T (MT2/IT3) 5 5 0G � IT � YST 4 4 0G � AFP/HCG 2 2 0

T(MT2/IT5)�YST 7 7 0MT � unclassified GCT 1 1 0Unclassified GCT 2 2 0 7.2 yrs (5.8–8.7 yrs) 2/0 100 0.2Diagnosed by markers 10 0 10 11 yrs (3 days–16.5 yrs 2.3 0 1.0

Craniopharyngioma 82 81 1 7.8 yrs (7.3 mos–17.7 yrs) 1.5 98.8 8.3Neuronal and mixed neuronal-glial

tumors 21 21 0 8.6 yrs (1.3–17.8 yrs) 0.8 100 2.1Ganglioglioma 12 12 0 8.5 yrs (1.4–17.8 yrs) 0.7 100 1.2Anaplastic ganglioglioma 2 2 0 5.2 yrs (2.6–7.8 yrs) 1 100 0.2DNT 5 5 0 10.4 yrs (6.6–14.6 yrs) 0.7 100 0.5Desmoplastic infantile

astrocytoma/ganglioglioma 1 1 0 5.2 yrs 1/0 100 0.1Central neurocytoma 1 1 0 8.6 yrs 0/1 100 0.1

Hamartoma 9 4 5 4.5 yrs (8.8 mos–12.8 yrs) 0.1 44.4 0.9Pineal parenchymal tumors 9 9 0 5.2 yrs (1.6–13 yrs) 0.8 100 0.9

Pineoblastoma 8 8 0 4.8 yrs (1.6–13 yrs) 1.0 100 0.8Pineocytoma 1 1 0 8.7 yrs 0/1 100 0.1

Tumors of meninges 19 19 0 10.9 yrs (11.9 mos–17.4 yrs) 0.7 100 1.9Meningiomas 13 13 0 10.6 yrs (11.9 mos–17.4 yrs) 0.6 100 1.3Dural sarcoma 5 5 0 10.6 yrs (1.6–14.6 yrs) 0.7 100 0.5

(continued)

2158 CANCER November 15, 2005 / Volume 104 / Number 10

Classification of TumorsWith reference to the World Heath Organization 2000classification,4 we classified and counted relative inci-dence of different types of brain tumors with eitherhistologic diagnosis or clinical diagnosis in the wholeseries. In this series of 986 patients, 842 (85.4%) pa-tients had histologic diagnoses, and the other 44 pa-tients had clinical diagnoses. The common entities oftumors were astrocytic tumors (31.1%), germ cell tu-mors (14.0%), medulloblastomas (13.2%), craniophar-yngiomas (8.3%), and ependymal tumors (5.7%). Rel-ative rare entities of tumors included neuronal andmixed neuronal glial tumors (2.1%), AT/RTs (2.1%),tumors of meninges (1.9%), tumors of choroids plexus(1.9%), tumors of cranial nerves (1.4%), oligodendro-glioma (1.2%), supratentorial PNET (1.2%), pituitaryadenomas (1.0%), pineal parenchymal tumors (0.9%),hamartomas (0.9%), chordomas (0.5%), hemangio-blastomas (0.3%), primary melanocytic tumors (0.2%),ependymoblastomas (0.1%), and astroblastoma(0.1%). For remaining 100 cases with tumors havingneither histologic nor clinical classification, there were73 brainstem tumors. The majority of these unclassi-fied tumors in brainstem, cerebral hemisphere, opticapparatus, and thalamus were most likely astrocytictumors (Table 2). Classified gliomas constituted 40.8%of tumors in this series. If most of the tumors withouthistologic diagnosis or clinical diagnosis were astro-cytic tumors or other gliomas, the proportion of glio-

mas would be up to 50% of primary brain tumors inchildren (Tables 2–3).

Specific entities of tumorsGerm cell tumors (GCTs). In this series, a total of 138GCTs were diagnosed at an average age of 10.7 yearswith a male to female ratio of 3.8:1. One hundred-fivepatients had histologic verification, and the remaining33 were diagnosed clinically. Of these 33 histologicallyunverified GCTs, 23 tumors were defined as germino-mas, and 10 tumors were defined as nongerminoma-tous malignant germ cell tumors (NG-MGCTs). Thediagnosis was made according to clinical features,neuroimaging, serum tumor markers (alpha-fetapro-tein [AFP], beta human chorionic gonadotropin [beta-hCG]), and response to radiation therapy and/or che-motherapy. The diagnosed entities of these tumorsincluded germinomas (54.4%), mature and immatureteratomas (15.9%), pure yolk sac tumors (7.3%), mixedGCTs (13.8%), unclassified GCTs (1.5%), and tumorsdiagnosed by tumor markers (7.3%). Among 19 casesof mixed GCTs, 16 cases had component of teratoma,11 cases had component of germinoma, 11 cases hadcomponent of yolk sac tumor, and 1 case had compo-nent of unclassified GCT. In two cases with compo-nent of germinoma, the diagnosis of mixed GCTs re-lied on elevated serum titer of AFP. Five of the 19mixed GCTs were initially teratomas (3 immature ter-atomas and 2 mature teratomas) in their first tumor

TABLE 2(continued)

Types of tumorsNo. ofpatients

Cases ofhistologydiagnosis

Cases ofclinicaldiagnosis Mean age (range)

Genderratio(M/F)


PercentageN � 986

Chondroma 1 1 0 15.3 yrs 1/0 100 0.1Tumors of peripheral nerve 14 14 0 12.7 yrs (5.4–17.9 yrs) 1.0 50 1.4

Vestibular schwannoma 13 13 0 12.8 yrs (5.4–17.9 yrs) 1.2 46.2 1.3MPNSTc 1 1 0 11.5 yrs 0/1 100 0.1

Pituitary adenomas 10 10 0 14.3 yrs (12.4–17.7 yrs) 2.3 100 1.0Primary melanocytic lesions 2 2 0 7.7 yrs (1.5–13.9 yrs) 0/2 100 0.2

Malignant melanomaTumors of uncertain histogenesis 2 0 0 10.8 yrs (6.7–14.8 yrs) 1/1 100 0.2

Hemangioblastoma —Chordoma 5 5 0 7.6 yrs (4.4–13 yrs) 1.5 100 0.5Tumor without histology clinical

diagnosisd 100 0 0 7.8 yrs (0.9 mos–17.9 yrs) 1.5 0 10.1

a PXA: pleomorphic xanthoastrocytoma.b Mixed GCTs: G � T(MT/IT) represents mixed GCTs with components of germinoma (G), mature teratoma (MT) or immature teratoma (IT); G � IT � YST represents mixed GCTs with components of germinoma

(G), immature teratoma (IT), and yolk sac tumor (YST); G � AFP/HCG represents mixed GCTs with components germinoma with elevated serum titer of AFP with/without elevated serum titer of HCG; T(MT/IT)�YST

represents GCTs with component of teratoma (mature teratoma or immature teratoma) and yolk sac tumor; MT � unclassified GCT represents mixed GCT with components of mature teratoma and unclassified

GCT.c MPNST: malignant Triton tumor arising from trigeminal nerve.d Tumors without histologic or clinical diagnosis included 73 tumors in brainstem, 5 tumors in cerebral hemisphere, 5 tumors in thalamus, 1 tumor in hypothalamus, 5 tumors in sellar-suprasellar region, 5 tumors

in pineal region, 2 tumors in basal ganglia, and 4 tumors in cerebellar vermis and 4th ventricle. The majority of these tumors may be astrocytic tumors.


resection. The pathologies changed to other types ofGCTs on recurrence.

Common locations of GCTs in these series werepineal (58, 42%), suprasellar–pineal (9, 6.5%), sellar–anterior third ventricle– hypothalamic region (36,26.1%), cerebral hemisphere including 25 basal gan-glia tumors and 2 cerebral lobe tumors (27, 19.6%),and ventricle (7, 5.1%). The location, age distribution,gender ratio, and percentage to the whole series ofdifferent types of GCTs are shown in Tables 3– 8. Inthese 138 GCTs, 111 tumors had serum tumor markers(AFP, beta-hCG) studies at diagnosis. Eighty-two pa-tients had both histologic diagnosis and serum tumormarker studies. Correlation with different histologictypes of GCTs and serum titers of tumor markers isshown in Table 4.

Atypical rhabdoid/teratoid tumors (AT/RTs). Among165 embryonal tumors, there were 131 medulloblas-tomas and 21 AT/RTs. AT/RTs constituting 2.1% of

primary brain tumors in this series. The mean age ofdiagnosis was 4.2 years (range, 0.5 mos to 10.7 yrs)with a male to female ratio of 1.6:1. These AT/RTs ofthe brain were located predominately in the cere-bellum (71.4%). Other locations included cerebralhemisphere, pineal– quadrigeminal region, and lat-eral ventricle. Cerebellar AR/RT mimics medullo-blastoma. The ratio of cerebellar medulloblastomato cerebellar AT/RTs was 131/15 (8.7:1) (Tables 2, 8).

Phacomatoses. In this series of primary pediatric braintumors, 39 (4.0%) children had phacomatoses. Theaverage age of diagnosis was 9.6 years (range, 1–18yrs). Male to female ratio was 1.5:1. Ten children hadNFI. Five of them had optic gliomas, with histologicdiagnosis of pilocytic astrocytomas in 2 patients. Fourpatients had astrocytic tumors including 1 in pons(pilocytic astrocytoma), 1 in cerebellar vermis (pilo-cytic astrocytoma), 1 in thalamus (pilocytic astrocy-toma), and 1 in hypothalamus (astrocytoma). The re-

TABLE 3Classification, Locations, Age Distribution, Gender Ratio, and Percentage of Specific Types of Primary Intracranial Germ Cell Tumors (N � 138/986)

Types of tumorsNo. ofcases

Cases ofhistologicdiagnosis Mean age (range)

Sex ratio(M/F)


PercentageN � 986

Total 138 105 10.6 yrs (3 days–18 yrs) 3.8/1 76 14.0Germinoma 75 52 11.9 yrs (1.3–18 yrs) 4 69.3 7.6

Suprasellar 19 15 11.8 yrs (5.6–16.5 yrs) 0.9 78.9 12.9Pineal 29 19 11.7 yrs (1.3–17.7 yrs) 8.7 65.5 2.9Suprasellar � pineal 7 6 14.5 yrs (8.7–18 yrs) 2.5 85.7 0.7Basal ganglia 18 10 11.1 yrs (7.3–14.4 yrs) 18/0 55.6 1.8Cerebral lobes 2 2 14.4 yrs (14–14.7 yrs) 2/0 100 0.2

Teratoma, mature 8 8 6.9 yrs (8.5 mos–15.3 yrs) 8/0 100 0.8Pineal 7 7 7.8 yrs (1.9–15.3 yrs) 7/0 100 0.7Deep hemisphere 1 1 8.5 mos. 1/0 100 0.1

Teratoma, immature 14 14 6.8 yrs (7 days–14.4 yrs) 13 100 1.4Suprasellar 1 1 6.0 yrs 0/1 100 0.1Pineal 4 4 12.0 yrs (7.2–14.3 yrs) 4 100 0.4Basal ganglia 2 2 13.1 yrs (11.7–14.5 yrs) 2/0 100 0.2Ventricle 7 7 2.1 yrs (7 days–13.2 yrs) 7/0 100 0.7

YST, pure 10 10 10.0 yrs (2.6–14.5 yrs) 1 100 1.0Suprasellar 5 5 11.3 yrs (7.7–14.5 yrs) 1/4 100 0.5Pineal 4 4 10.3 yrs (8.3–12.5 yrs) 3 100 0.4Cerebellum 1 1 2.6 yrs 1/0 100 0.1

Mixed GCT 19 19 10.1 yrs (1.6–15.4 yrs) 2.8 100 1.9Suprasellar 6 6 8.9 yrs (1.6–13.1 yrs) 1/1 100 0.6Pineal 8 8 10.5 yrs (3–15.4 yrs) 3/1 100 0.8Suprasellar � pineal 1 1 15.0 yrs 1/0 100 0.1Basal ganglia 4 4 10.1 yrs (8.8–11.5 yrs) 4/0 100 0.4

Unclassified GCT 2 2 7.2 yrs (5.8–8.7 yrs) 2/0 100 0.2Suprasellar 1 1 8.7 yrs 1/0 100 0.1Pineal 1 1 5.8 yrs 1/0 100 0.1

Diagnosed by markers 10 0 11 yrs (3 days–16.5 yrs) 2.3 0 1.0Suprasellar 4 0 11.7 yrs (7.1–16.5 yrs) 1 0 0.4Pineal 5 0 9.3 yrs (3 days–13.5 yrs) 4 0 0.5Suprasellar � pineal 1 0 16.4 yrs 1/0 0 0.1


maining 1 patient had a germinoma at the basalganglia.5 Thirteen children had NFII. All of them hadbilateral vestibular schwannomas. Cranial meningio-mas were also recorded in 6 patients. Twelve patientshad tuberous sclerosis with subependymal giant cellastrcytomas (SEGAs). Ten of them had histologic di-agnosis. Two patients had neurocutaneous melanosisand histologic proof of intracranial malignant mela-nomas. Basal cell nevus syndrome (Gorlin syndrome)was observed in 2 children with medulloblastomas(Table 5).

Radiation-induced tumors. We observed 7 patientswho developed second tumors after radiation therapyfor primary brain tumors. Their primary tumors werecerebellar medulloblastomas in 4 patients, sellar cra-niopharyngioma in 1 patient, pineal germinoma in 1patient, and posterior temporal residue pilocytic as-trocytoma in 1 patient. The durations of time afterresection and radiation therapy to diagnosis of secondtumors were from 2.8 –21.1 years. These radiation-induced tumors included basal cell epithelioma ofscalp and meningioma of cerebral convexity devel-oped in a girl at 16.3 years after radiation for hermedulloblastoma at 2 years old. Multiple supratento-rial meningiomas were found at 21.1 years after cra-niospinal irradiation (CSI) for medulloblastoma at 5.5

years of age. An anaplastic oligodendroglioma withtumoral hemorrhage was found 20.5 years after CSI formedulloblastoma in a girl aged 9 years. A left frontalpole meningioma was diagnosed 20 years in a girl afterCSI for medulloblastoma at 5.1 years of age. Atypicalmeningioma of the tentorium was found 13.1 yearsafter local radiation of a residue pilocytic astrocytomaof the posterior temporal region. A glioblastoma mul-tiforme of pons was diagnosed 8 years after radiationtherapy for a craniopharyngioma in a girl 4 years old.Angiosarcoma in soft tissue of occipital region oc-curred at 2.8 years after radiotherapy for a pinealgerminoma. These tumors were excluded from thestudy series of primary brain tumors.

Locations of tumorsIncluding 91 cases of pineal– quadrigeminal tumors,there were 575 (58.3%) supratentorial tumors and 405(41.1%) infratentorial tumors. Another 6 (0.6%) pa-tients had both supra- and infratentorial tumors andall of them had traits of neurofibromatosis (Table 6).Infratentorial tumors predominated only in thegroups aged 5, 6, and 8 years. There was almost equaldistribution of supratentorial and infratentorial tu-mors in the age groups of 4 and 18 years. Supratento-rial tumors predominated in all of the other yeargroups (Fig. 2). The neuroanatomic distributions of

TABLE 4Correlation of Serum Tumor Markers (AFP, HCG) and Different Types of Intracranial GCTs with Histologic Diagnosis

Histologic typesNo. ofpatients

Serum AFP ng/mL Serum HCG mIU/mL

ND N E ND N E

Germinoma 40 0 38 2 13.3 20.1 3 30 7 44.6 77859.1 151980.8 6555128

Teratoma, mature 7 2 5 0 0 7 0Teratoma, immature 9 0 0 9 21.5 116 2 6 1 27.6

26 53738 55292.8 901193.9

YST, pure 9 0 0 9 1293 2650 1 5 3 28.8 8041355 5427 1871590 61091876 73042177

Mixed GCT 17 1 3 13 21.5 146 3 7 7 10.5 17524.9 365 30.8 280238.0 366 61.4 331249.4 1874 15654.1 202659.8 2126120

AFP: alpha-fetoprotein; HCG: human chorionic gonadotropin; ND: not done; N: normal (within reference range); E: elevated (higher than reference range)


tumors were cerebellum 24.2% (239), cerebral hemi-sphere 19.7% (194), sellar-suprasellar–anterior thirdventricular– hypothalamus region 19.2% (189), brainstem 12.2% (120), ventricles 8.3% (82), single pinealregion tumors 7.5% (74), tumors of both suprasellarand pineal regions 1.0% (10), thalamus 4.7% (46), dura1.5% (15), and bilateral vestibular schwannoma 1.3%(13) (Table 7).

Types of tumors in specific neruoanatomic locations.Common tumors in cerebral hemisphere were astro-cytic tumors (49.0%), GCTs (13.9%), ependymal tu-mors (10.3%), gangliogliomas (7.2%), and oligoden-droglioma (6.2%). In cerebral hemisphere, themajority of GCTs (23/25 patients) originated in thedeep hemisphere—the basal ganglia region. Commontumors of sellar–anterior III ventricular– hypothalamicregion were craniopharyngiomas (43.4%), astrocytictumors (21.2%), GCTs (19.1%), pituitary adenomas(5.3%), and hamartomas (4.2%). For gliomas in thislocation, most were optic pathway gliomas, and 3 of37 patients had no histologic confirmation. In supra-sellar region, 28 of 36 GCTs had histologic diagnosis.

Types of GCTs in this area were germinomas (52.8%),immature teratoma (2.8%), mixed GCTs (16.7%), pureyolk sac tumors (13.9%), unclassified GCT (2.8%), andtumors diagnosed by tumor markers (11.1%). Twotypes of tumors occurred in the hypothalamus, theastrocytic tumors and the hamartomas. For pinealtumors, there were 74 patients with tumors in thepineal region alone. Another 10 patients had bothsuprasellar and pineal tumors. The average age atdiagnosis of these tumors was 10.3 years with a maleto female ratio of 5.5:1. Tumors in the pineal or su-prasellar–pineal regions were GCTs (79.8%), pine-oblastomas (9.5%), astrocytic tumors (2.4%), and pine-ocytoma (1.2%). Common tumors in thalamus regionwere astrocytic tumors (71.7%) and PNETs (15.2%).Cerebellar tumors were mainly medulloblastomas(54.8%), astrocytic tumors (33.5%), and AR/RTs (7.1%).In cerebellar vermis, 65.3% tumors were medulloblas-toma. In cerebellar hemisphere, 63.5% were astrocytictumors. For brain stem tumors, among 120 patients ofprimary brain stem tumors, only 46 (38.3%) had his-tologic diagnosis, and the majority was astrocytic tu-mors. These tumors were distributed at the midbrain(7), pons (94), and the medulla and cervicomedullaryjunction (18). The distribution of 46 histologically

TABLE 5Phacomatoses and Brain Tumors

PhacomatosesNo. ofcases Intracranial tumors

NFI 10 Optic gliomas 5pilocytic astrocytoma 2no histologic diagnosis 3a

Pilocytic astrocytoma 3thalamus, cerebellar vermis, pons

Astrocytoma 1hypothalamus

Germinoma 1Basal ganglia

NFII 13 Bilateral vestibular schwannomashistologic diagnosis 6no histologic diagnosis 7b

Meningiomas 6histologic diagnosis 6

Tuberous sclerosis 12 Subependymal giant cellastrocytomas 10histologic diagnosis 10no histologic diagnosis 2c

Basal cell nevus syndrome 2 Medulloblastomas 2Cerebellar vermis 1Cerebellar hemisphere 1

Neurocutaneous melanosis 2 Malignant melanomas 2

a Three sellar region tumors in NFI patients without histologic diagnosis were classified as optic

gliomas.b Bilateral tumors in internal meatus of 7 NFII patients without histologic diagnosis were classified as

vestibular schwannomas.c Among 13 patients with SEGA, 12 patients presented clinical features of tuberous sclerosis, and 2 of

these SEGAs had no histologic diagnosis.

TABLE 6Distribution of Pediatric Brain Tumors in Taiwan

No.supratentorialtumors (%)

No.infratentorialtumors (%)

No. supra- &infratentorialtumors (%)

Shih et al. NDMC, Taipei,1977a N � 126 67 (53.2) 59 (46.8)

Ho et al. NTUH, Taipei,1969–1978b N � 87 53 (60.9) 34 (39.1)

Wong et al. Taipei VGH,1978–1985 Age � 15yrsc N � 171 99 (57.9) 72 (42.1)

Wong et al. Taipei VGH,1978–1994 Age � 15yrsd N � 501 291 (58.1) 207 (41.3) 3 (0.6)

Wong et al. Taipei VGH,1975–2004 Age � 15yrse N � 935 540 (57.8) 390 (41.7) 5 (0.5)

Wong et al. Taipei VGH,1975–2004 Age � 18yrsf N � 986 575 (58.3) 405 (41.1) 6 (0.6)

a If 7 arteriovenous malformations and 4 arachnoid cysts were excluded, the ratio of supratentorial and

infratentorial tumors would be 49.6 –50.4%.b If 22 histologically unverified brain stem gliomas were included, the ratio of supratentorial and

infratentorial tumors would be 48.6 –51.4%.c Data from study of 171 cases of pediatric brain tumors of � 15 yrs of age after the CT brain scan was

used as the diagnostic tool in Taipei VGH.d Data from study of 501 cases of pediatric brain tumors of � 15 yrs of age with diagnostic images.e Data from study of 935 cases of pediatric brain tumors of � 15 yrs of age with diagnostic images.f Data from study of 986 cases of pediatric brain tumors of � 18 yrs of age with diagnostic images.


proved tumors in brainstem were 41 astrocytic tumors(midbrain 3, pons 23, medullar/cervicomedullary 15),3 gangliogliomas (pons 2, medulla 1), 1 ependymo-blastomas (pons 1), and 1 hemangioblastoms (pons 1).These histologic findings demonstrated that the ma-jority of brainstem tumors (89.1% in this series) wereactually brainstem astrocytic tumors. Ventricular tu-mors were mainly posterior fossa ependymomas(43.9%), choroids plexus tumors (23.2%), SEGAs(14.6%), GCTs (8.5%), and meningiomas (4.9%). Thetwo major types of tumors of meninges were menin-giomas (56.3%) and meningeal sarcomas (31.3%) (Ta-ble 8).

Location distributions of specific primary brain tu-mors. Astrocytic tumors and gangliogliomas distributeboth supratentorially and infratentorially in brain.Other types of primary brain tumors in children tendto arise in specific neuroanatomic locations. In thisseries, the most common distributions of astrocytictumors were cerebral hemisphere (30.9%), cerebellum(26.1%), brain stem (13.4%), optic appraratus-sellar–hypothalamus region (13.0%), thalamus (10.7%), andSEGAs in the lateral ventricle (4.2%). Ependymal tu-mors distributed in cerebral hemisphere (35.7%) andin fourth ventricle of the posterior fossa (64.3%). Alloligodendrogliomas and mixed gliomas originated incerebral hemisphere. The 3 most common locationsfor GCTs were pineal and suprasellar–pineal region

(48.6%), sellar–anterior third ventricle– hypothalamicregion (26.1%), and basal ganglia and cerebral lobes(19.6%). All medulloblastomas occurred within cere-bellum, and the majority of them in cerebellar vermis(86.3%). AT/RTs, which may mimic medulloblasto-mas, in cerebellum (71.4%), but they were also distrib-uted in cerebral hemisphere, ventricle, and pineal–quadrigeminal region. Supratentorial PNETs werefound mainly in thalamus (58.3%), cerebral hemi-sphere (16.7%), and sellar region (16.7%). All cranio-pharyngioma in this series were sellar or suprasellartumors with various extensions and directions of ex-tension. Neuronal and mixed neuronal glial tumorswere mainly in cerebral hemisphere (66.7%), cerebel-lum (14.3%), brain stem (14.3%), and hypothalamus(4.8%). Meninigiomas were tumors arising from duralmatter (64.3%), but there were also tumors in ventricleor cerebral hemisphere. Meningeal sarcomas all orig-inated from dura of anterior temporal region (Table 9).

DISCUSSIONIn this study, specific tumor data that highlight thecharacter of this series were 1) average age of diagno-sis � 7.8 years; 2) male to female ratio of 1.4/1; 3) highincidence of germ cell tumors (14%); 4) AT/RTs rep-resenting 2.1% of tumors in this series; 5) Thirty-nine(3.9%) patients with traits of phacomatoses; 6) sevenpatients who developed second tumors after radio-therapy for primary tumors; 7) supratentorial tumors(58.3%) predominated over infratentorial tumors(41.8%); 8) neuroanatomical locations of tumors com-mon in cerebellum, cerebral hemisphere, sellar–ante-rior third ventricular– hypothalamic region and brainstem; 9) tumors in pineal and basal ganglia regionsmostly germ cell tumors.

Increased incidence of brain tumors in childrenhas been observed and reported in the West. Alsoreported is an increased incidence of astrocytoma andmedulloblastoma and/or primitive neuroectodermaltumor (M/PNET).6 –11 In Japan, a study of incidence ofchildhood brain tumors in Hokkaido Prefectureshowed increased incidence.12 According to the regis-ter of the childhood brain tumor (age � 18 yrs) from17 representative hospitals by the Childhood CancerFoundation, R.O.C. Taiwan from 1995 to 2002, theannual registered cases varied from 116 to 144 withannual incidence rate of 1.84, 2.02, 2.03, 2.4, 2.09, 2.25,2.03, 2.23/100,000, respectively. There was no evi-dence of trend increase. This collection representedthe majority of childhood brain tumors diagnosed inTaiwan but was still not a national registration.

We compared the reported data of ChildhoodBrain Tumor Consortium (CBTC), hospital series ofUniversity Hospital of Munster (UHM), the collectionof Brain Tumor Registry of Japan (BTRJ), the hospital

TABLE 7Neuroanatomic Locations of Pediatric Brain Tumors

Cerebral hemisphere 19.7%Lobe 15.2%Deep hemisphere 4.5%

Sellar-anterior III ventricle-hypothalamus 19.2%Hypothalamus 1.7%

Thalamus 4.7%Pineal 7.5%Suprasellar-pineal 1.0%Cerebellum 24.2%

Vermis 17.2%Hemisphere 6.4%Brachium 0.2%NOSa 0.2%

Brainstem 12.2%Midbrain 0.7%Pons 9.5%Medulla 1.5%Cervicomedulla 0.3%NOSa 0.1%

Ventricle 8.3%Extraparenchymatous 1.9%

Bil, vestibular schwannoma 1.3%Dura 1.5%

a Not otherwise specified in location.


series of Seoul National University Hospital (SNUH) ofKorea, and our series.13–16 The CBTC collected data on3291 children with CNS brain tumors. These patientsreceived first tumor surgery at one of the CBTC cen-ters before January 1, 1979 before age 21 years. Theseries of UHM consisted of 319 cases of brain tumorsof up to 17 years of age (age 0 –17 yrs) with biopsysamples. Patient data were collected over a 17-yearperiod (1984 –2000) by the Institute of NeuropathologyMunster from 7 regional neurosurgical departments.In BTRJ (1969 –1996), there were 4280 cases of child-

hood brain tumors under the age of 15 years (age 0 –14yrs). Among them, 210 patients had no histologic di-agnosis. In the SNUH series, a series of 677 patientswith age younger than 16 years old, only surgicallytreated patients were included. The Taipei VGH series,a series of 986 patients, age younger than 18 years, andall of the patients with computed tomography (CT) orMRI diagnosis were recruited. Among them, 953 pa-tients were younger than 16 years of age. The threeseries in Asia had similar mean age and gender ratio ofpatients. The mean age of diagnosis, gender ratio, andrelative frequency of common tumor entities of thefive comparative series are listed in Table 10. Exceptthe series of CBTC, the other 4 series were predomi-nant in supratentorial tumors that were 53.3%, 52.8%,60.0% and 58.3%, respectively. In the recently reportedseries of primary pediatric brain tumors in children,supratentorial tumors predominated over infratento-rial tumors.14,16,17 By using chi-square test, statisticalcomparison of relative incidence of tumors in theseseries was performed (data not shown). Except cho-roid plexus tumor and pineal parenchymal tumor,significant statistical difference (P � 0.05) of relative

TABLE 8Types of Tumors in Specific Neuroanatomic Locations

LocationsNo. ofcases

Cases of tissuediagnosis

Cases of clinicaldiagnosis Types and percentage (%) of tumors

Cerebral hemisphere 194 179 7 Ast GCT Epen Gang Olig49.0 13.9 10.3 7.2 6.2

Sellar-anterior IIIV-Hypothalamus 189 166 17 Cran Ast GCT Pit Ham43.4 21.2 19.1 5.3 4.2

Pineal & suprasellar-pineal 74 54 15 GCT PB Ast PC10 8 2 79.8 9.5 2.4 1.2

Thalamus 46 41 0 Ast PNET71.7 15.2MDB Ast AT/RT Gang D.I. Gang

Cerebellum 239 236 0 54.8 33.5 7.1 0.8 0.4Vermis 170 167 0 65.3 22.9 6.5 0.6Hemisphere 63 63 0 25.4 63.5 6.4 1.6Brachium 4 4 0 25 50 25NOS* 2 2 0 100

Ast Gang EB HemBrainstem 120 46 0 34.2 2.5 0.8 0.8

Midbrain 7 3 0 42.9Pons 94 27 0 24.5 2.1 1.0Medulla/cervicomedulla 18 16 0 83.3 5.6NOS* 1 0 0

Ventricle 82 79 2 Epen CPT SEGA GCT Men43.9 23.2 14.6 8.5 4.9

Meninges 15 15 0 Men Sar Chon Ast53.3 33.3 6.7 6.7

Ast: astrocytic tumor; AT/RT: atypical teratoid/rhabdoid tumor; Chon: chondroma; CPT: choroid plexus tumor; Cran: craniopharyngioma; D.I. Gang: desmoplastic infantile gangliglioma; EB: ependymoblastoma;

Epen: ependymal tumor; Gang: ganglioglioma; GCT: Germ cell tumor; Ham: hamartoma; Hem: hemangioblastoma; MDB: medulloblastoma; Men: meningioma; Olig: oligodendroglial tumor; PB: pineoblastoma; PC:

pineocytoma; Pit: pituitary adenoma; PNET: primitive neuroepithelial tumor; Sar: sarcoma; SEGA: subependymal giant cell astrocytoma.aNOS: not otherwise specified in location.

FIGURE 2. Chart shows the distribution of supratentorial ( including pineal–

quadrigeminal) versus infratentorial tumors.


incidence existed in astrocytic tumor, medulloblas-toma, germ cell tumor, craniopharyngioma, ependy-moma, and oligodendroglioma. Comparing our serieswith the series of CBTC and the series of UHM indi-vidually, significant statistical difference (P � 0.0125)of relative incidence existed in both astrocytic tumorsand germ cell tumors. There was no such statisticaldifference between our series and the series of BTRJand the series of SNUH. The results showed geo-graphic differences in incidences existed between

countries and geographic regions for astrocytic tumorand other tumors. We have no explanation for therelatively higher incidence of astrocytic tumors in thetwo series from Western countries. For the extremesignificant difference of incidence in germ cell tumorbetween the two series of Western countries and the 3Asian series (P � 0.0001), genomic difference shouldbe considered.

In this series, we classified part of those histologicunverified tumors through their own specific clinical

TABLE 9Location Distribution of Specific Primary Brain Tumors in Children

Types of tumorsNo. ofcases

Cases withhistologicdiagnosis

Neuroanatomic location and percentage of tumors

CerebralHem

Sellar-anteriorIII V-hypothalamus

Pineal andsuprasellar-pineal Ventricle Cerebellum

Brainstem Thalamus Meninges

Ast 307 305 30.9 13.0 0.7 4.2 26.1 13.4 10.75 0.3Epen 56 56 35.7 64.3a

Olig 12 12 100M. glioma 7 7 100GCT 138 105 19.6 26.1 48.6 5.1 0.7MDB 131 131 100b

AT/RT 21 21 9.5 4.8 4.8 81.0c

PNET 12 12 16.7 16.7 8.3 58.3Cran 82 81 100NMNGT 21 21 66.7 9.5 14.3 4.8Men 14 14 7.1 28.6 64.3M. Sa 5 5 100

Ast: astrocytic tumor, AT/RT: atypical teratoid/rhabdoid tumor; Cran: crnaiopharyngioma; Epen: ependymal tumor; GCT: germ cell tumor; MDB: medulloblastoma; M. glioma: mixed glioma; NMNGT: neuronal and

mixed neuronal glial tumor, Men: meningioma; M. Sa: meningeal sarcoma; Olig: oligodendroglial tumor; PNET: primitive neuroepithelial tumor.a 4th ventricular ependymoma.b cerebellar vermis 86.3%, cerebellar hemisphere 12.2%, cerebellar location undetermined 1.5%.c cerebellar vermis 11 (52.4%), cerebellar hemisphere 4 (19.1%), brachium cerebellum 2 (9.5%).

TABLE 10Comparison of Case Collections for Average Age, Gender Ratio, and Relative Frequency of the Most Common Childhood Brain Tumors

SeriesCBTCbefore 1979

UHM(1984–2000)

BTRJ(1969–1996)

SNUH(1959–2000)

Taipei VGH(1975–2004)

No. of patients 3291 319 4080 699 986Gender ratio M/F 1.2 1.6 1.3 1.4 1.4Age range in yrs 0–20 0–17 0–14 � 16 � 18Average age 7.8 7.8Supratentorial tumors 40.9% 53.3% 52.8% 60.0% 58.3%

% % % % Mean age M/F % Mean age M/FAstrocytic tumor 40.3 47.3 28.2 25.7 7.4 1.0 31.0 7.5 1.0Medulloblastoma 20.0 16.3 11.9 17.9 7.7 1.7 13.1 7.0 1.9Germ cell tumor 2.3 2.5 15.3 11.2 10.0 1.7 14.0 10.6 3.8Craniopharyngioma 6.8 5.6 8.9 12 8.0 1.5 8.3 7.7 1.5Ependymal tumor 10.9 3.8 4.5 5.0 5.1 1.4 5.7 6.0 1.3Oligodendroglial tumor 1.3 — 0.9 3.5 8.8 0.8 1.2 7.9 1.4Choroid plexus tumor 2.0 0.9 1.9 1.3 4.1 3.5 1.9 2.2 1.4Pineal parenchymal tumor 1.0 0.9 0.9 1.3 8.3 1.3 0.9 5.2 0.8

Case collection of Childhood Brain Tumor Consortium (CTBC), the hospital series of University Hospital of Munster (UHM), Brain Tumor Registry of Japan (BTRJ), Seoul National University Hospital of Korea (SNUH)

and the Taipei VGH series of Taiwan (Taipei-VGH).


features. These tumors were GCTs, specific entities ofCNS tumors of phacomatoses, and hypothalamichamartomas. For tumors of neither histologic diagno-sis nor clinical classification, the majority of thesetumors were brainstem tumors, and most of themwere actually astrocytic tumors. For the present clin-ical practice, histologic diagnosis is not absolutelynecessary for diagnosis and management of GCTs,optic pathway gliomas, vestibular schwannomas, SE-GAs, hypothalamic hamartomas, and pontine gliomas.

Primary intracranial GCTs consist of a variety oftumor types with different degrees of malignancy. Thereported incidences of GCTs in children were high inJapan and Korea as compared with incidence in West-ern countries.14 –16,18 We had a similar high incidence.For GCTs, over 40% of these tumors were germino-mas.15,19 It was 54.3% in our series in children. Intra-cranial GCTs mainly appear in pineal, sellar region,basal ganglia and ventricules. In the pineal region,usually � 70% tumors were GCTs.20,21 In our series, itwas 79.8%. The region of basal ganglia is a significantlocation for germ cell tumors. In a reported series of107 patients with primary germ cell tumors, 16 werelocated in the basal ganglia or the thalamic region.22

In our series, among 138 children with GCTs, 25 werelocated in the basal ganglia, which constituted of67.6% of tumors in the basal ganglia.

Serum titers of AFP and beta-hCG in 82 GCTs inthis series correlated with their histologic entities andan earlier report from this institution.23 Serum AFPlevels were usually higher in pure yolk sac tumors thanin immature teratomas and mixed GCTs. The serumAFP titers in pure yolk sac tumors were more than1000 ng/mL in 9 of 9 cases versus 1 of 9 in immatureteratoma and 3 of 13 in mixed GCTs. Normal serumlevels of AFP were observed in 5 of 5 mature terato-mas. In 2 of 40 germinomas, a low level of elevation ofserum AFP titers was found, but staining for AFP wasnegative in these 3 tumors. The serum hCG levels werehigh in tumors with syncytiotrophoblastic giantcells.23 In this series, there was no histologic diagnosisof choriocarcinomas. Elevated serum titers of beta-hCG occurred in 7 of 37 germinomas (range, 44.6 –6555 mIU/mL), 3 of 8 pure yolk sac tumors (range,28.8 – 804 mIU/mL), and 7 of 14 mixed GCTs (range,10.5–3312 mIU/mL). Serum beta-hCG titers were nor-mal in 7 of 7 mature teratomas. Only 1of 7 immatureteratoma had a low elevation of serum beta-hCG. (Ta-ble 4).

CNS AT/RT was a rare entity of embryonal tu-mors. The incidence in children in 2 reported serieswere 1.3% and 1.6%.14,24 In this series, it was 2.1% ofall primary intracranial tumors in children. These tu-mors are most common in infants of � 2 years of age.The average ages of diagnosis were 17 months and 29

months in 2 reported series as compare with 4.2 yearsin ours.25,26 The diagnosis relied on the specific inter-est of experienced neuropathologists to separate thisentity of tumor from PNET/MB. The diagnosis criteriaincluded morphologic features (rhabdoid cells, smallPNET/MB cells, epithelial components, spindle cells),and immunohistologic profiles.26,27

Phacomatoses represents a diverse group of syn-dromes that is characterized by retinal lesion, cutane-ous signatures, and CNS manifestation, especiallytumors. In the current series, the incidence of phaco-matoses was 3.9% including NF1, NF2, tuberous scle-rosis, BCNS, and neurocutaneous melanosis. Clinicaldiagnosis for brain tumors could be made in some ofthese syndromes, such as optic gliomas in NF1, me-ningiomas and bilateral vestibular schwannomas inNF2, and SEGAs in tuberous sclerosis. From a series inDenmark, among 911 children under 15 years of age,there were 21 patients who had neurofibromatosis.Among them, 16 had an astrocytoma (12 in the opticpathway), 2 had a supartentorial meningioma, and 1had a vestibular schwannoma.17 von Hippel–Lindaudisease with CNS hemangioblastomas usually pre-sented in adult patients. This entity did not occur inthe current series.

Radiation-induced brain tumor is a potentialcomplication of radiation therapy for brain tumors inadult and children. In the current series, radiation-induced meningiomas, glioblastoma, anaplastic oligo-dendroglioma, and soft tissue angiosarcoma were ob-served in 7 patients after radiotherapy for malignantor benign brain tumors. All of these second tumorshave been reported in the literature. Among them,radiation-induced gliomas and meningiomas weremost common.28 –31

ConclusionEpidemiologic studies of pediatric brain tumors areusually based on population-based surveys of child-hood cancer registries, childhood brain tumor regis-tries, or hospital series. Annual incidence rates or age-specific incidence rates in children can be obtained ina country or in a geographic region. The pitfalls forpopulation-based survey of brain tumors in childrenthrough childhood cancer registries or childhoodbrain tumor registries were incompleteness of patientregistration that may lead to underestimation. Biasalso exists for not including benign tumors or tumorswithout histologic verification for registry.32,33 Forhospital series, incompleteness occurred in series in-volving only tumors with surgery or with histologicdiagnosis. In the current series from Taipei VGH, wecollected data on 986 patients with primary pediatricbrain tumors in the years of 1975–2004. Among them,842 (85.4%) patients had histologic diagnosis. This


large hospital series included all primary brain tumorsdiagnosed by CT or MRI. Although it is not a study ofpopulation-based brain tumor registry, it may still bedata representative of primary pediatric brain tumorsin Taiwan.

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