Journal of Neuro-Oncology 60: 43–52, 2002.© 2002 Kluwer Academic Publishers. Printed in the Netherlands.

Clinical Study

Supratentorial primitive neuroectodermal tumors in adults

Dong Gyu Kim1, Dong Yeob Lee1, Sun Ha Paek1, Je G. Chi2, Gheeyoung Choe2 and Hee-Won Jung1

1Department of Neurosurgery, 2Department of Pathology, Seoul National University College of Medicine,Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea

Key words: primitive neuroectodermal tumor (PNET), supratentorial, adult, prognosis, calcification, Ki-67

Summary

A retrospective clinical analysis was made of 12 patients with supratentorial primitive neuroectodermal tumor(PNET) who ranged in age from 20 to 62 years (median 24) and were managed at Seoul National University Hospitalbetween January 1987 and December 1997. Six patients were male and six were female. Most presented withsymptoms of increased intracranial pressure and mean duration of symptoms was four months (range: 1–12 months).The tumors were located in the posterior parieto-occipital area in six cases and the mean diameter of mass of thesetumors was 5.3 cm. The characteristic magnetic resonance image finding was a large well-demarcated lobulatingmass with intratumoral cyst, necrosis, and/or hemorrhage. Calcification was seen in five out of six patients whounderwent computed tomography scan. All patients underwent craniotomy and three of them received subsequentoperations due to local recurrence. Ten patients received postoperative whole neuraxis radiation therapy and fivepatients received additional chemotherapy. Mean survival after diagnosis was 86 months. The patients havingintratumoral calcifications are all alive and two out of three showing a Ki-67 labelling index greater than 30% diedat eight and 20 months after operation, respectively. In conclusion, supratentorial PNET must be included, evenin adults, in the differential diagnoses if a tumor has characteristic radiological features. The adult supratentorialPNET seemed similar to that of children in the clinical features and the prognosis. Intratumoral calcifications andthe Ki-67 labelling index might be prognostic factors, however, it should be considered that the sample size is toosmall and not all patients were evaluated.

Introduction

Primitive neuroectodermal tumor (PNET) is an undif-ferentiated neoplasm arising from the germinal matrixof the primitive neural tube. In 1973, Hart andEarle introduced the term primitive neuroectodermaltumor describing embryonal neoplasm outside thecerebellum, morphologically similar to medulloblas-toma [1]. In 1993, the World Health Organization(WHO) classification of brain tumors defined allprimitive neuroectodermal tumors of central nervoussystem as PNET, regardless of the location; inside(PNET/medulloblastoma) and outside (supratentorialPNET) the cerebellum [2]. Supratentorial PNET inchildren is not a rare intracranial neoplasm and muchis known about the clinical manifestation, treatment,and prognosis. However, only sporadic case reports ofsupratentorial PNET in adults have been reported inthe literature [3–8]. This study examined twelve adult

cases of supratentorial PNET managed at one insti-tute during the recent eleven years, possibly the largestseries in this field.

Clinical materials and methods

Between 1987 and 1997, during the magnetic reso-nance imaging (MRI) era at Seoul National UniversityHospital, 56 patients were diagnosed with supraten-torial PNET based on histological findings. Twelvepatients were aged over 20 years and consideredadult cases (0.46% of all primary brain tumors inadults during the same period). A retrospective anal-ysis was performed using clinical charts, radiologicalinvestigations, and pathological examinations.

On the basis of surgical records and postoperativecomputed tomography (CT)/MRI, the extent of resec-tion was assessed and defined as follows: gross total

44

resection (GTR) in cases of no enhancement on post-operative imaging, near total resection (NTR) in casesof >90% tumor removal, subtotal resection (STR) incases of >50% tumor removal, partial resection (PR)in cases of 10–50% tumor removal, or biopsy in casesof <10% removal. M-stage of Chang’s classificationfor PNET/medulloblastomas was evaluated by wholespine MR images and cerebrospinal fluid (CSF) exam-ination with lumbar spinal tapping prior to surgeryor within two weeks following initial surgery in allpatients [9].

The image follow-ups of the brain and whole spinehad been performed every 3–6 months after initialsurgery for first two years and then yearly. Tumorprogression was defined as an increase in measuredtumor volume of more than 25% associated with clin-ical deterioration. During the follow-up period, CSFsampling was not performed. The end points in eval-uation of survival of this study were death or the lastfollow-up.

Pathological examination was performed usingarchival material preserved on glass slides using H&Estains, Masson’s trichrome stains, and immunohis-tochemical stains for glial fibrillary acidic protein(GFAP) and synaptophysin. The term PNET wasapplied to undifferentiated embryonal tumors whichare morphologically similar to medulloblastomas.Labelling for Ki-67 and p53 protein was performed ineight cases using formalin-fixed, paraffin-embeddedarchival material, which were routinely processedaccording to standard histological techniques. Fivemicrometer-thick sections placed on silanized slideswere immunohistochemically stained with the Ki-67monoclonal antibody (Zymed, CA, 1 : 100) and p53monoclonal antibody (Zymed, CA, 1 : 800) usingLSAB kits (DAKO, Denmark) following antigenretrieval by microwave oven irradiation. A total of1000 cells were counted in five representative areas.The labelling index (LI) of Ki-67 or p53 was cal-culated as the ratio of labelled cells to the totalnumber of tumor cells and expressed as percentage.Immunohistochemical expression of synaptophysinwas classified as neuronal differentiation, and expres-sion of GFAP, as glial differentiation. Perivascularpseudorosette formation with GFAP expression ofperivascular fibrillary processes was classified asependymal differentiation.

The Kaplan–Meier method was used for the cal-culation of patients’ survival time. The log-rank testwas used to compare two groups in univariate analy-sis. The Cox proportional hazard model was used in

multivariate analysis. P -value <0.05 was consideredsignificant in all analysis.

Results

Clinical and radiological findings

The age of patients at diagnosis ranged from 20 to62 years (median 24), and the male : female ratiowas 6 : 6. The duration of symptoms before diagnosisranged from 1 to 12 months (mean 4). The most com-mon initial symptoms were those related to increasedintracranial pressure. Three patients presented withfocal neurologic deficits. One patient presented withgeneralized tonic clonic seizure. Upon neurologicalexamination at admission, visual field defects werepresent in six cases. Four of these cases presentedwith homonymous hemianopsia and the others withunilateral hemianopsia. Papilledema was detected insix patients. Facial nerve palsy, motor dysphasia, hemi-paresthesia, and hemiparesis were detected in one case,respectively.

All patients underwent MRI, and in six cases, CTwas also performed. The tumors involved the parieto-occipital area in six, the temporal lobe in four, andthe frontal lobe in two. There was no case of pinealPNET in this study. The size of the tumors was mea-sured between three and eight centimeters in longestdimension (mean 5.3). On MR images, the lobulat-ing mass showed heterogeneous signal intensity inboth T1- and T2-weighted images. The demarcationbetween the mass and adjacent normal tissue was rel-atively good in eleven cases. One case showed poordemarcation. The solid portion of tumor was slightlyhypointense on T1-weighted images and hyperintenseon T2-weighted images. On postcontrast T1-weightedMR image, the solid portion of mass showed stronghomogeneous enhancement in all cases. Intratumoralcyst (four cases), necrosis (three cases), and/or hemor-rhage (two cases) were present. Moderate to severe per-itumoral edema was present in most patients (Figure 1).On precontrast CT, the mass was isodense or hyper-dense in five cases, which suggested hypercellularityof the tumor. Intratumoral calcification was observed infive cases. Single globular calcification was observedin four and multiple small calcifications in one.Postcontrast CT showed a moderate enhancement inthe solid portion of the mass. Focal areas of promi-nent vascularity were seen in five out of six casesthat had undergone cerebral angiography (Figure 2).

45

Figure 1. Case 7. (Left) T2-weighted MR image showing a mass with heterogeneous signal intensity in the right parieto-occipital area.The area with bright high signal intensity with smooth wall suggesting intratumoral cyst was seen in the anterior portion of the mass.The solid portion is hyperintense and severe peritumoral edema is also observed. (Center) T1-weighted MR image showing a sharplydemarcated mass with heterogeneous signal intensity. The solid portion of mass is hypointense. (Right) Strong homogeneous enhancementwas observed on the postcontrast T1-weighted MR image.

MR spectroscopy was performed at the solid portion ofmass in two patients. The results showed an increaseof the choline peak, decrease of the N -acetyl aspar-tate peak, and the presence of a lactate peak, pos-sibly the nonspecific findings of a malignant braintumor. Preoperative radiological differential diagnosesincluded anaplastic oligodendroglioma, glioblastoma,and metastatic brain tumor. The clinical and radiolog-ical findings of the twelve patients are summarized inTable 1.

Treatment

All patients underwent craniotomy for both diagno-sis and decompression. Stereotactic biopsy was per-formed in one patient before craniotomy. Gross totalremoval was performed in seven cases and subtotalremoval in five. The gross appearance was purplishgray or pinkish in color with lobulating contourand the masses in eleven cases were well demar-cated. One patient who underwent STR had poordemarcation both on operation field and preoperativeMR images. Four cases were subtotally resected dueto profuse bleeding or adjacency to the eloquent area.Nine patients recovered uneventfully after the cran-iotomy, whereas tumor bed bleeding, brain swelling,and hemiparesis developed in three patients. Therewas no operative mortality. There was no case ofcerebrospinal dissemination in whole spine MRI andCSF examination performed prior to surgery or within

two weeks following surgery. Whole neuraxis radia-tion therapy was performed subsequent to the histo-logical diagnosis in ten cases, although none of thepatients showed spinal seeding. One patient declinedradiation therapy and the other deteriorated rapidly dueto the progression of the tumor. Ten patients receivedthe planned dose of radiation between 5040 and5580 cGy at primary site (mean 5410 cGy), between3000 and 3600 cGy at whole brain (mean 3450 cGy),and between 2700 and 3600 cGy at whole spine (mean3250 cGy). Four of five patients who had residualtumors after initial surgery underwent whole neuraxisradiation therapy. Chemotherapy following three kindsof regimen (CCNU, vincristine, and cisplatin/CCNU,vincristine, and procarbazine/vincristine) was per-formed without any protocol in five patients; as anadjuvant therapy following radiation in four and as apalliative therapy of recurrent tumor in one. Amongfive patients who underwent chemotherapy, one patienttreated with vincristine experienced pancytopenia andanother patient treated with CCNU, vincristine, andprocarbazine experienced skin eruption and nausea.Seven additional surgical procedures were performeddue to local recurrence in three cases. One patientunderwent additional surgery due to radiation necro-sis. Two patients received stereotactic radiosurgeryfor the recurrent lesion after craniotomy and radia-tion therapy. None of the patients exhibited tumorseeding along the CSF during the follow-up periodin MRI.

46

Pathological findings

Upon gross inspection, the tumors had relatively well-demarcated margins and lobulated external surfaces.The cut surfaces were pinkish gray and exhibited asolid, maintaining lobular pattern (Figure 3). Cysticchange, necrosis, and calcification were focally notedin some cases.

Upon microscopic examination, the cellular tumorconsisted of small undifferentiated cells with hyper-chromatic, round to oval nuclei (Figure 4). The cyto-plasm of tumor cells was scanty and ill-defined. Thetumor cells were arranged in cords or nests surroundedby loose or sometimes desmoplastic connective tis-sue. Mitoses were present and mitotic activity wasvariable. Microscopic calcifications were noted in five

A B

C D

Figure 2. (Continued)

47

E F

Figure 2. Case 3. (A) T2-weighted MR image showing a mass with heterogeneous signal intensity in the left parieto-occipital area. Thehyperintense area suggesting intratumoral necrosis is seen within the mass. Severe peritumoral edema is also seen. (B) In postcontrastT1-weighted MR image, the solid portion of mass shows strong homogeneous enhancement. (C) The precontrast CT scan showing themass with heterogeneous density. A single globular calcification is seen within the mass. Peritumoral edema is also seen. (D) PostcontrastCT scan shows moderate enhancement. (E) Left vertebral angiography, antero-posterior and (F) lateral view, showing hypervascularitysupplied by the left posterior cerebral artery.

cases and necroses were present in six cases. Elevenout of twelve cases disclosed neuronal or glial differ-entiation. Immunohistochemical expression of synap-tophysin was noted in seven cases, and expressionof GFAP was noted in seven cases (Table 1). Fourcases showed neuronal differentiation only and threecases, glial differentiation only. Three cases displayedboth neuronal and glial differentiation. One case exhib-ited mixed glial and mesenchymal differentiation. Onecase revealed neither neuronal nor glial differentiation.Three cases with glial differentiation only, two casesdisplayed perivascular pseudorosettes and expressionof GFAP in perivascular fibrillary processes. They werediagnosed as PNET with ependymal differentiation.Upon immunohistochemical examinations, the meanvalue of Ki-67 LI was 20.6% ranging from 2% to 38%and that of p53 LI was 7.6% ranging from 3% to 17%.

Prognosis and prognostic factors

The mean duration of follow-up was 43 months(ranging from 8 to 124 months). Two patients diedof local recurrence at eight and 20 months after theoperation. However, ten are still alive. The mean sur-vival time for all patients was 86 months from thetime of operation. The overall 1- and 3-year survivalrate were 91% and 75%, respectively, and progression

free survival at 1- and 3-year were 91% and 63%,respectively. The Karnofsky performance scales (KPS)of those who are still alive are over 70 with the meanfollow-up duration of 49 months. The patients havingintratumoral calcifications are all alive and two out ofthree showing Ki-67 LI greater than 30% died at eightand 20 months after surgery, respectively. Mean sur-vival time and one-year survival rate of three patientswith a Ki-67 LI greater than 30% were 17 monthsand 67%, respectively. Patient’s age at diagnosis, pre-senting symptom (increased intracranial pressure vs.others), presence of intratumoral necrosis, cyst, andhemorrhage, type of histological differentiation, extentof resection at the initial operation (GTR vs. STR),chemotherapy, size of tumor (<5 vs. ≥5 cm), and thep53 LI showed no relation to survival.

Discussion

Clinical and radiological findings

Most patients presented with symptoms and signsof increased intracranial pressure. No characteristicsymptom and sign of supratentorial PNET was present,however, visual field defect was a frequent neurolog-ical deficit due to predilection of this tumor for theparieto-occipital and temporal area.

48

Tabl

e1.

Sum

mar

yof

twel

vepa

tient

sof

supr

aten

tori

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ET

inad

ults

Cas

eA

gePr

esen

ting

Sym

ptom

Loc

.Si

zeC

a2+M

RE

xten

tof

Adj

uvan

tPa

thol

ogic

Ki-

67p5

3FU

Rec

urre

nce

KPS

atN

o.(y

rs),

sym

ptom

dura

tion

(cm

)in

findi

ngs

rese

ctio

nth

erap

yfin

ding

sL

IL

I(m

os)

last

FUse

xor

sign

(mos

)C

T(d

iffe

rent

iatio

n)(%

)(%

)

124

,FII

CP

1o

5N

DC

yst

GT

RR

T,C

Rx

Glia

l38

1220

Yes

Exp

ire

226

,FII

CP

3f

3+

−G

TR

ND

Epe

ndym

alN

DN

D58

Yes

903

20,M

IIC

P7

p-o

5+

−ST

RR

TG

lial&

26

48N

o10

0m

esen

chym

al4

21,M

IIC

P2

o7

+−

GT

RR

T,C

Rx

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l&16

938

No

80ne

uron

al5

23,M

IIC

P12

t8

+H

emor

rhag

eST

RR

TN

euro

nal

153

45N

o90

necr

osis

627

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rest

hesi

a10

p4

+−

GT

RR

T,C

Rx

NO

SN

DN

D98

No

907

26,M

IIC

P1

p-o

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DC

yst

GT

RR

T,C

Rx

Neu

rona

l36

1724

No

100

853

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asia

3t

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Nec

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DG

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304

8N

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n9

20,F

Hem

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esis

2f

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GT

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rona

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312

4Y

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1024

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ND

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No

9011

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D16

No

100

1262

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No

70ne

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Ca2+

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atio

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Rx:

chem

othe

rapy

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pute

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oval

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P:in

crea

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intr

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nial

pres

sure

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arno

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perf

orm

ance

scal

e,L

I:la

belli

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dex,

mos

:mon

ths,

Loc

.:lo

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n,M

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e,M

R:m

agne

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ND

:not

done

,NO

S:no

toth

erw

ise

spec

ified

,o:o

ccip

ital,

p:pa

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al,R

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T:r

adia

tion

ther

apy,

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:sub

tota

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oval

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yrs:

year

s,+:

pres

ence

,−:a

bsen

ce.

49

Figure 3. The cut surface of the tumor. Note pinkish grayand solid cut surface with lobular pattern and relativelywell-demarcated margin.

Figure 4. Photomicrograph of the tumor. Note highly cellularsmall undifferentiated cells with frequent mitoses. The nucleiare hyperchromatic, round to oval, and the cytoplasm are scanty(H&E, original magnification × 400).

Suspicion of supratentorial PNET in adults, thoughrare, seems very important for the preoperative diagno-sis. Supratentorial PNET in adults usually looks like ahigh-grade astrocytoma in CT or MR image. However,there are several different findings from high-gradeastrocytoma. Tumor cyst, calcification, and lobulating

contour with good demarcation which are unusual find-ings in the high-grade astrocytoma, are the charac-teristic findings in the supratentorial PNET in adult.Differentiation between anaplastic oligodendrogliomaand supratentorial PNET is sometimes problematic,however, supratentorial PNET usually exhibits gooddemarcation. Although not performed in all patientsin this study, CT scan seems important because pres-ence of intratumoral calcification which is helpful indifferential diagnosis from metastatic brain tumor andhigh-grade astrocytoma except anaplastic oligoden-droglioma, could not be detected in MR image. Theradiological findings of adult supratentorial PNET inour series are very similar to that of another reportedseries [8].

The clinical and radiological findings of supraten-torial PNET in adults are similar to those of PNET inchildren and ten out of twelve patients of our serieswere in third decade [10]. This suggests that supraten-torial PNET in adults might be a variant form of child’sdisease with delayed onset, as was displayed in cranio-pharyngioma. However, there are a few cases suggest-ing presence of more delayed onset variant, which isunusual in craniopharyngioma. Two patients who were58-year and 62-year old in our series and several caseswho were older than 50 years in the previous reportsmay be considered as more delayed onset variants [3,4].The presence of two peaks in the age profile for adultsupratentorial PNET; twenties and middle age, must bedocumented further.

Treatment and prognosis

Radical resection followed by whole neuraxis radia-tion was the mainstay of management in our series.The degree of resection might be not a major fac-tor in the prognosis of adult supratentorial PNET.GTR could be performed in seven cases because ofgood demarcation, large tumor cyst, and superficiallocation. In five cases, subtotal removal was donedue to profuse bleeding, poor demarcation, and/oradjacency to eloquent area, such as basal ganglia orinternal capsule. However, there was no difference insurvival between total-removal and subtotal-removalgroups. Four of five patients who had residual tumorsafter initial surgery and underwent no other adjuvanttherapy but whole neuraxis radiation therapy wereall alive to the last follow-up without progression(16–48 months). STR followed by radiation therapyseems a reasonable treatment option particularly when

50

GTR of the tumor might lead to further neurologicaldeficit.

Postoperative whole neuraxis radiation therapy wasperformed in all ten cases in apprehension to cran-iospinal seeding frequently observed in the supratento-rial PNET in children [11–13], although none of themshowed any evidence of craniospinal seeding. None ofthese patients exhibited tumor seeding along the CSFduring the follow-up period. The median survival afterdiagnosis was 86 months. Additionally chemother-apy with different chemotherapeutic regimens wasperformed postoperatively case by case without anyprotocol in some cases of our series. Comparisonof survival rates between patients with and withoutadjuvant chemotherapy showed no significant differ-ence. However, two patients who have been alive for98 and 124 months after first diagnosis had under-gone both whole neuraxis radiotherapy and adjuvantchemotherapy after initial GTR.

In three cases, the tumors recurred after GTR and allof them received subsequent operation. Two of thesepatients are still alive with a KPS of 90 at 58 monthsand 80 at 124 months of the last follow-up, respectively.Radiosurgery might be performed as an adjuvant ther-apy because of good demarcation and delineation of themass in the radiological examinations. Radiosurgerywas performed in two recurrent cases, but the role ofradiosurgery must be evaluated further.

The outcome of adult supratentorial PNET in thisstudy seems to be good compared to that of childsupratentorial PNET in the previous reports. The3-year survival rate of supratentorial PNET in childrenranges from 29% to 57%, whereas the mean survivaland 3-year survival rate are 86 months and 75%,respectively, in our series [14–18]. Among previousreports, the most favorable outcome was reported bythe Children’s Cancer Group (CCG). They conductedstudy CCG-921 from May 1986 until June 1992 forpatients aged 18 months to less than 22 years withdiagnosis of 203 posterior fossa medulloblastomasand 52 supratentorial PNETs [15]. They reported a 3-year overall survival of 57% for supratentorial PNETsand 73% for pineal PNET. However, they excludedthe patients under the age of 18 months and includedthose over the age of 18 years who might influenceoutcomes of their cohort. In 1999, Pediatric Divi-sion of our department reported 28 cases of pediatricsupratentorial PNET under the age of 17 (8 months to17 years) [19]. There was no difference in the clinicalmanifestation and radiological findings between chil-dren and adults. Among 28 pediatric patients, GTR

was performed in 17, NTR in three, STR in seven,and biopsy in one. For 25 patients who completedwhole neuraxis radiation therapy, median survival was68 months and the 3-year survival rate was 73%. Thismight be due to absence of CSF seeding cases in thisstudy. The limited use of radiation therapy due to itsdeleterious effect on children under age of three andcases of local and CSF tumor spread might be thereasons for the difference. The 3-year survival rateof 73% for child supratentorial PNET experienced inour institute was longer than that previously reported[14–19]. Radical resection of tumors and high percent-age (82%) of patients who had underwent radiationtherapy even in the case of a child, might explain thismore positive outcome.

The cells of PNET have a pleuripotentiality of dif-ferentiations and, in fact, the histological findings ofPNETs have shown a variety of differentiation in ourseries as well [20,21]. Janss et al. reported a differenceof biological behavior according to the histological dif-ferentiation; the supratentorial PNET with glial differ-entiation showed a 6.7-fold increased risk of recurrence[22]. The biological differentiations of the two caseswho died in our series were glial in one and glial andneuronal in the other.

In child supratentorial PNET, young age(1.5–3 years), tumor necrosis, and evidence of tumordissemination at diagnosis are poor prognostic fac-tors, whereas pineal location and completeness ofinitial surgical resection are good prognostic factors[14–16,19,23]. However, age, tumor necrosis, andextent of removal were not related to prognosis andthere were no cases of CSF dissemination or pineallocation in this adult series. Instead, all five patientshaving intratumoral calcifications in CT scans werealive to the last follow-up whereas two out of threepatients with a Ki-67 LI greater than 30% showedpoor outcomes. Immunohistochemical Ki-67 stainingwas performed to evaluate the proliferative potentialof adult supratentorial PNET and its influence onprognosis. The prognostic significance of Ki-67 LIin astrocytoma has been well reported [24]. For childsupratentorial PNET in our institute, patients withKi-67 LI greater than 10% tend to have shorter survival[19]. Results of our adult series were similar to thechild series. Despite small sample size and incompleteevaluation of this study, intratumoral calcification andKi-67 LI (<30%) were thought to be good prognosticfactors of adult supratentorial PNET in our series.

Though this study is the largest series of adult supra-tentorial PNET examined at one institute, the number of

51

cases is not large enough to verify the clinical featuresand biologic behavior of adult supratentorial PNET.

This study suggested that (1) supratentorial PNETmust be included, even in adult, in the differential diag-nosis if a tumor has characteristic radiological features;(2) the adult supratentorial PNET seemed similar to thatof children in the clinical features and the prognosis;(3) intratumoral clacification and the Ki-67 LI mightbe prognostic factors, however, it should be consideredthat the sample size is too small and not all patientswere evaluated.

Acknowledgement

This work was partially supported by a grant fromSeoul National University Hospital.

References

1. Hart MN, Earle KM: Primitive neuroectodermal tumors ofthe brain in children. Cancer 32: 890–897, 1973

2. Kleihues P, Burger PC, Scheithauer BW: The new WHOclassification of brain tumours. Brain Pathol 3: 255–268,1993

3. Bellis EH, Salcman M, Bastian FO: Primitive neuroectoder-mal tumor in a 57-year-old man. Surg Neurol 20: 30–35,1983

4. Ho YS, Hsieh LL, Chen JS, Chang CN, Lee ST, Chiu LL,Chin TY, Cheng SC: p53 gene mutation in cerebral prim-itive neuroectodermal tumor in Taiwan. Cancer Lett 104:103–113, 1996

5. Kuratsu J, Matsukado Y, Seto H, Nonaka N, Sueyoshi N:Primitive neuroectodermal tumor arising from the thalamusof an adult – case report. Neurol Med Chir (Tokyo) 26:30–34, 1986

6. Louis DN, Hochberg FH: Cerebral primitive neuroectoder-mal tumor in an adult, with spinal cord metastasis after18-year dormancy. J Neuro-Oncol 9: 77–80, 1990

7. Miyazawa T, Ueno H, Hatashita S: ‘Undifferentiated’cerebral primitive neuroectodermal tumor in a youngadult – case report. Neurol Med Chir (Tokyo) 34: 759–762,1994

8. Pickuth D, Leutloff U: Computed tomography and magneticresonance imaging findings in primitive neuroectodermaltumours in adults. Br J Radiol 69: 1–5, 1996

9. Chang CH, Housepian EM, Herbert C Jr: An operative stag-ing system and a megavoltage radiotherapeutic techniquefor cerebellar medulloblastomas. Radiology 92: 1351–1359,1969

10. Figeroa RE, el Gammal T, Brooks BS, Holgate R,Miller W: MR findings on primitive neuroectoder-mal tumors. J Comput Assist Tomogr 13: 773–778,1989

11. Halperin EC, Friedman HS, Schold SC Jr, Fuchs HE,Oakes WJ, Hockenberger B, Burger PC: Surgery,hyperfractionated craniospinal irradiation, and adjuvantchemotherapy in the management of supratentorial embry-onal neuroepithelial neoplasms in children. Surg Neurol 40:278–283, 1993

12. Kosnik EJ, Boesel CP, Bag J, Sayers MP: Primitive neuroec-todermal tumors of the central nervous system in children.J Neurosurg 48: 741–746, 1978

13. Parker JC Jr, Mortara RH, McCloskey JJ: Biological behav-ior of the primitive neuroectodermal tumors: significantsupratentorial childhood gliomas. Surg Neurol 4: 383–388,1975

14. Albright AL, Wisoff JH, Zeltzer P, Boyett J, Rorke LB,Stanley P, Geyer JR, Milstein JM: Prognostic factors inchildren with supratentorial (nonpineal) primitive neuroec-todermal tumor. A neurosurgical perspective from theChildren’s Cancer Group. Pediatr Neurosurg 22: 1–7,1995

15. Cohen BH, Zeltzer PM, Boyett JM, Geyer JR, Allen JC,Finlay JL, McGuire-Cullen P, Milstein JM, Rorke LB,Stanley P: Prognostic factors and treatment results forsupratentorial primitive neuroectodermal tumors in chil-dren using radiation and chemotherapy: a Children’s CancerGroup randomized trial. J Clin Oncol 13: 1687–1696,1995

16. Dirks PB, Harris L, Hoffman HJ, Kumphreys RP, Drake JM,Rutka JT: Supratentorial primitive neuroectodermal tumorsin children. J Neuro-Oncol 29: 75–84, 1996

17. Gaffney CC, Sloane JP, Bradley NJ, Bloom HJ: Primitiveneuroectodermal tumours of the cerebrum. Pathology andtreatment. J Neuro-Oncol 3: 23–33, 1985

18. Jakacki RI, Zeltzer PM, Boyett JM, Albright AL, Allen JC,Geyer JR, Rorke LB, Stanley P, Stevens KR, Wisoff J:Survival and prognostic factors following radiation and/orchemotherapy for primitive neuroectodermal tumors ofthe pineal region in infants and children: a report of theChildren’s Cancer Group. J Clin Oncol 13: 1377–1383,1995

19. Yang HJ, Nam DH, Wang KC, Kim YM, Chi JG, Cho BK:Supratentorial primitive neuroectodermal tumor in children:clinical features, treatment outcome and prognostic factors.Childs Nerv Syst 15: 377–383, 1999

20. Gould VE, Jansson DS, Molenaar WM, Rorke LB,Trojanowski JQ, Lee VM, Packer RJ, Franke WW: Prim-itive neuroectodermal tumors of the central nervous sys-tem. Patterns of expression of neuroendocrine markers, andall classes of intermediate filament proteins. Lab Invest 62:498–509, 1990

21. Gould VE, Wiedenmann B, Lee I, Schwechheimer K,Dockhorn-Dworniczak B, Radosevich JA, Moll R, FrankeWW: Synaptophysin expression in neuroendocrine neo-plasms as determined by immunocytochemistry. Am JPathol 126: 243–257, 1987

22. Janss AJ, Yachnis AT, Silber JH, Trojanowski JQ, LeeVM, Sutton LN, Perilongo G, Rorke LB, Phillips PC: Glialdifferentiation predicts poor clinical outcome in primitiveneuroectodermal brain tumors. Ann Neurol 39: 481–489,1996

52

23. Mikaeloff Y, Raquin MA, Lellouch-Tubiana A,Terrier-Lacombe MJ, Zerah M, Bulteau C, Habrand JL,Kalifa C: Primitive cerebral neuroectodermal tumorsexcluding medulloblastomas: a retrospective study of30 cases. Pediatr Neurosurg 29: 170–177, 1998

24. Jaros E, Perry RH, Adam L, Kelly PJ, Crawford PJ,Kalbag RM, Mendelow AD, Sengupta RP, Pearson ADJ:Prognostic implications of p53 protein, epidermal growth

factor receptor, and Ki-67 labelling in brain tumors. Br JCancer 66: 373–385, 1992

Address for offprints: Dong Gyu Kim, Department of Neurosurgery,Seoul National University Hospital, 28 Yongon-dong, Chongno-gu,Seoul 110-744, Korea; Tel.: 82-2-760-2874; Fax: 82-2-744-8459;E-mail: gknife@plaza.snu.ac.kr