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C O M N O V E M B E R 2 0 0 8 C A S E 1

POSTERIOR FOSSA TUMOR IN A 12 YEAR-OLD BOY

CLINICAL HISTORY

A 12-year-old male was admitted to our hospital complaining of 

right upper limb tremor, loss of the normal capacity to modulate

fine voluntary movements with his right hand and headache, lasting

for over a month. On neurological examination dysdiadochokine-

sia and intention tremor of the right upper limb was noted. A

computed tomography (CT) scan was performed and revealed a

large lesion expanding in the right cerebellar hemisphere, com-

 pressing the fourth ventricle which was occluded. Magnetic reso-

nance imaging (MRI) of the brain demonstrated the same space-

occupying lesion in the fourth ventricle measuring approximately

4 ¥ 3.8 ¥ 4 cm. It was hypointense on T1-weighted images (Fig. 1),

medium intense on T2 and FLAIR sequences, and heterogeneously

enhanced after gadolinium administration (Fig. 2). The lesion was

surrounded by edema and caused displacement of the cerebellar 

vermis and pons. A suboccipital midline craniotomy was per-

formed, the cerebellar vermis was split and the lesion was totallyexcised.

GROSS AND MICROSCOPIC

PATHOLOGY

Macroscopically, the resected tumor had a varied appearance with

evidence of old and recent hemorrhage, necrosis and areas of firm

tissue. Histological examination revealed extensive infiltration of 

cerebellar tissue by a cellular malignant tumor composed of round 

and spindle cells with eosinophilic cytoplasm, moderate-severe

nuclear atypia and brisk mitotic activity (Fig. 3). Characteristic

features were: a) the presence of numerous giant mononuclear and 

multinuclear neoplastic cells, b) the presence of geographic necro-

sis (necrosis with palisading) (Fig. 4), c) glomeruloid microvascu-

lar hyperplasia, and d) the infiltrating pattern of invasion into the

adjacent parenchyma. Immunohistochemistry showed rare GFAP

expression in the neoplastic cells, while there was no expression of 

synaptophysin, neurofilament, Neu-N (a marker of neurons) and 

Epithelial Membrane antigen (EMA). The INI-1 protein retained 

nuclear expression in the tumor component. The Ki-67/MIB-1 pro-liferative index was detected in>70% ofthe nuclei(Fig. 5) and p53

 protein in 90% of them. No EGFR expression was observed.

Figure 1.

Figure 2.

Figure 3.

Figure 4. Figure 5.

doi:10.1111/j.1750-3639.2009.00278.x

341Brain Pathology 19 (2009) 341–342

© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology

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DIAGNOSIS

Glioblastoma multiforme.

DISCUSSION

Brain neoplasms are the most common childhood cancer after leu-

kemia, accounting for approximately 25% of all pediatric cancers(5). Both the histological type and location of pediatric brain

tumors differ from those occurring in the adult population. Low-

grade astrocytomas and medulloblastomas are the most frequently

encountered in children, whereas anaplastic astrocytomas and glio-

 blastoma multiforme (GBM) are more common in adults and are

extremely rare in children (6, 8).

In our case the radiological differential diagnosis included 

medulloblastoma, ependymoma and low grade astrocytoma. The

constellation of CT and MRI findings suggested medulloblastoma

as the most likely diagnosis. Atypical teratoid/rhabdoid tumor (AT/

RT) should also be included in the differential diagnosis but is

usually encountered earlier in life.

CerebellarGBMs are extremely rare, especially in children, with

only occasional reports (1, 3, 4). From a neuropathological per-

spective, it is very important that the tumor fulfill the diagnostic

criteria for GBM (significant pleomorphism, hypercellularity,

mitoses and especially necrosis with palisading and glomeruloid 

type vascular hyperplasia) (2). On histological examination primi-

tive neuroectodermal tumors (PNETs) and medulloblastomas

that are common tumors in the posterior fossa in children, may

also exhibit pseudopalisading necrosis. Nevertheless, PNETs and 

medulloblastomas are usually positive for synaptophysin by immu-

nohistochemistry. In our case there was no expression of neuronal

antigens (synaptophysin, Neu-N and neurofilaments). Further-

more, there was no convincing evidence of neuronal or neuroblas-

tic differentiation, such as Homer Wright rosettes. AT/RT, a tumor 

that also shares the morphologic features of both medulloblastomaand PNET with epithelial, primitive neuroepithelial and mesenchy-

mal differentiation, was included in the differential diagnosis.

However, AT/RT tumors lack INI1 immunohistochemical expres-

sion in the nucleus and our case showed positive INI1 staining.

Furthermore, anaplastic oligodendrogliomas may also exhibit

 pseudopalisading necrosis but they are relatively uncommon and 

the increased pleomorphism was also more compatible with

glioblastoma.

Regarding the management of cerebellar lesions, a gross-total

resection, if feasible, would be the appropriate treatment in all

cases. Post-operative radiation in children older than 3 years is no

longer in question; given that in few cases treated without radiation

survival was less than a month. The question is whether the radia-

tion therapy should be delivered to the tumor bed alone or the entire

neuraxis. The radiation of entire neuraxis has now been established 

as the treatment of choice,given that the incidence of CSF dissemi-

nation in patients who did not received craniospinal irradiation was

high and with elective neuraxis irradiation there was nearly an

elimination of this complication (1, 4, 5, 7). Chemotherapy may

hold a role in pediatric cerebellar GBM but its usefulness has not

 been well studied due to the limited number of patients. However, it

definitely offers a reasonable treatment available to very young

children in whom the effect of brain radiation would be devastat-

ing. The same treatment options are offered for high-grade diffuse

 pontine gliomas, however in such cases a gross total resection is

unfeasible. The prognosis of cerebellar GBMs is poorer even com-

 pared to supratentorial GBMs. In a series of 14 patients with cer-

ebellar GBM, 11 died after a mean survival time of 9.9 monthswhereas the remaining patients were alive with a mean follow-up

 period of 24 months (7).

In conclusion, GBM should be kept in mind in the differential

diagnosis of the lesions in the posterior fossa. A gross total resec-

tion should be always attempted, where possible, in order a better 

outcome to be achieved.

REFERENCES

1. Campbell JW, Pollack IF (1996) Cerebellar astrocytomas in children. J 

 Neurooncol  28:223–231.

2. Chamberlain MC, Silver P, Levin VA (1990) Poorly differentiated 

gliomas of the cerebellum. A study of 18 patients. Cancer 65:337–340.

3. Georges PM, Noterman J, Flament-Durand J (1983) Glioblastoma of the cerebellum in children and adolescents. Case report and review of 

the literature. J Neurooncol 1:275–278.

4. Kopelson G (1982) Cerebellar glioblastoma. Cancer 50:308–311.

5. Salazar OM (1981) Primary malignant cerebellar astrocytomas in

children: a signal for postoperative craniospinal irradiation. Int J 

 Radiat Oncol Biol Phys 7:1661–1665.

6. Sanders RP, Kocak M, Burger PC, Merchant TE, Gajjar A, Broniscer A

(2007) High-grade astrocytoma in very young children. Pediatr Blood 

Cancer 6: [Epub ahead of print]

7. Ushio Y, Arita N, Yoshimine T, Ikeda T, Mogami H (1987) Malignant

recurrence of childhood cerebellar astrocytoma: case report.

 Neurosurgery 21:251–255.

8. Viano JC, Herrera EJ, Suarez JC (2001) Cerebellar astrocytomas: a

24-year experience. Childs Nerv Syst 17:607–610.

Contributors:

Evriviadis Mpairamidis1 MD, George A Alexiou1 MD,

Kalliopi Stefanaki2 MD, PhD, Ilias Manolakos1 MD,

George Sfakianos1 MD, PhD, Neofytos Prodromou1 MD, PhD1  Department of Neurosurgery, 2  Department of Pathology,

Children’s Hospital “Agia Sofia”, Athens, Greece.

ABSTRACT

Cerebellar glioblastoma multiforme (GBM) has rarely been

reported in children. We report a case of a 12-year-old child com-

 plaining of right upper limb tremor, loss of the normal capacity to

modulate fine voluntary movements with right hand and headache,

lasting for over a month. Radiological studies (CT and MRI)

revealed a lesion of the right cerebellar hemisphere. The tumor was

surgically excised and the histological examination revealed the

 presence of a GBM. The differential diagnosis of the lesions in the

 posterior fossa should include GBM.A gross total resection should 

 be always attempted in order to achieve a better clinical outcome,

although nearly all of these tumors recur.

Correspondence

342 Brain Pathology 19 (2009) 341–342

© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology