BRAIN

SPINE

Primitive Neuroectodermal Tumors (PNET) include: Medulloblastoma
(M); retinoblastoma; pineoblastoma; neuroblastoma; esthesioneuroblastoma; ependymoblastoma; polar spongioblastoma.

Epidemiology
M is a common tumoral lesion in pediatric population, accounting for 25% of all childhood brain tumors (15% - 20% of central nervous system tumors in patient younger than 20 years of age). Median age of diagnosis is 5 years, with 80% of cases being diagnosed in the first 15 years. In adult M accounts for only 1% of all adult brain tumors. The incidence in children is approximately five cases per million people per year. M:F ratio ranges from 1,4:1,0 to 4,8:1,0. Usually M arises in the cerebellar vermis, in the apex of the roof of the fourth ventricle (fastigium). Approximately 50% of adult medulloblastomas are laterally located, compared with less than 10% of childhood medulloblastomas.

Clinical
Clinical presentation is with signs of increased intracranial pressure caused by ostruction of the fourth ventricle and truncal & appendicular ataxia.

Pathology
The external granule cell layer of the cerebellum is thought to be cell layer of origin. Histologically , the tumor is highly cellular and consists of small cells with frequent mitoses and single-cells necrosis. Microinvasion of surrounding neural tissues (facial colliculus) and extension into the overlying leptomeninges and subarachnoid space is typical (“sugar coating”). Hystological subtypes: classic; desmoplastic; nodular; glial; pleomorphic; rhabdomyoblastoma (rare); malanocytic (rare). Compared with pediatric medulloblastomas, the desmoplastic variant is more common in adults (15% in pediatric cases). A few familial cases have been reported in the context of genetic syndromes: Basal Cell Nevus Syndrome (autosomal dominant syndrome- mutations in the PTCH gene on chromosome 9q - rare in classical M); Turcot’s Syndrome (germ-line mutations of APC on chromosome 5q are of autosomal dominant inheritance); Wilms’sTumor; Li-Fraumeni’s Cancer Syndrome (germ-line p53 mutation on chromosome 17p). Some authors suggests a role for the hedgehog signaling pathway in M formation. The Rac 1 GTPase (controlling PAK kinases and COX-2) may contribute to M invasion and metastasis.

Neuroimaging
CT findings: hyperdense (90%); Ca2+ in up 20%; hemorrhage rare; small intratumoral cyst/necrosis (40-50%).
MR findings: T1WI - hypointense to gray matter; T2WI - near gray matter intensity; T1 C+ - >90% enhance, linear icing-like enhancement over brain surface (Zuckerguss).

Differential diagnosis
Cerebellar pilocytic astrocytoma; ependymoma; choroid plexus papilloma; atypical teratoid/rhabdoid tumor; dorsally exophytic brainstem glioma.

Treatment
The goal treatment of choice is tumoral removal and radiotherapy completed as soon as possible (35-40 Gy to whole craniospinal axis + 10-15 Gy boost to tumor bed and to any spinal mets seen). Chemotherapy is no standardized and usually reserved for recurrence, for poor risk patients or for children < 3 yrs age. Ventriculoperitoneal shunt is necessary in 30-40% of children (seeding risk = 10-20%). Prognostic factors are: Chang M stages; sex; the extent of surgery or postoperative residual disease of more than 1,5 cm2; the absence or presence of brainstem invasion; age; the histological subtype; the radiation dose to the posterior fossa. Seeding: 10-35% of Ms have seeded the cranio-spinal axis at the time of diagnosis (extraneural mets = 5% of patients). Late relapse (some studies report recurrences as late as 14 years after treatment), which is uncommon among pediatric patients, occurs much more frequently among adult patients.
Poor prognosis: age < 4 yrs; disseminated lesions; inability to perform gross-total removal; histological differentiation along glial, ependymal, or neuronal lines - 35-50% chance of beeing free of disease at 5 yrs. Good-risk patients: no residual tumor on post-op MRI and negative CSF results with over 75% 5-year survival.

References