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 dysdiadochokinesia 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, compressing the fourth ventricle which was occluded. Magnetic resonance 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 performed, the cerebellar vermis was split and the lesion was totally excised.

Figure 1.

Figure 2.

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 necrosis (necrosis with palisading) ( Fig. 4 ), c) glomeruloid microvascular 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 proliferative index was detected in >70% of the nuclei ( Fig. 5 ) and p53 protein in 90% of them. No EGFR expression was observed.

Figure 3.

Figure 4.

Figure 5.

DIAGNOSIS

Glioblastoma multiforme.

DISCUSSION

Brain neoplasms are the most common childhood cancer after leukemia, 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 glioblastoma 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.

Cerebellar GBMs are extremely rare, especially in children, with only occasional reports 1, 3, 4. From a neuropathological perspective, 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 primitive 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 immunohistochemistry. In our case there was no expression of neuronal antigens (synaptophysin, Neu‐N and neurofilaments). Furthermore, there was no convincing evidence of neuronal or neuroblastic differentiation, such as Homer Wright rosettes. AT/RT, a tumor that also shares the morphologic features of both medulloblastoma and PNET with epithelial, primitive neuroepithelial and mesenchymal differentiation, was included in the differential diagnosis. However, AT/RT tumors lack INI1 immunohistochemical expression 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 radiation 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 dissemination 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 devastating. 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 compared to supratentorial GBMs. In a series of 14 patients with cerebellar GBM, 11 died after a mean survival time of 9.9 months whereas 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 resection should be always attempted, where possible, in order a better outcome to be achieved.

ABSTRACT

Cerebellar glioblastoma multiforme (GBM) has rarely been reported in children. We report a case of a 12‐year‐old child complaining 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.