Pathogenesis and Pathophysiology. Almost two thirds of these tumors are located in the midline cerebellum, and over 90 percent are located in the vermis with encroachment on the cisterna magna. Laterally placed tumors are more common in adults. The macroscopic appearance is that of a soft friable tumor with central necrosis. In children, these tumors are moderately demarcated, but in adults they are highly demarcated. Microscopically, neuropathological analysis has attempted to define these tumors as a subset in a larger category termed primitive neuroectodermal tumors (PNET). y This classification stems from the belief that these tumors result from the germinal neuroepithelium during embryogenesis and thus can differentiate into tumor cells with neuronal, glial, or ependymal characteristics.
Medulloblastomas are often classified as small blue cell tumors with little cytoplasm and pseudorosettes, which may signify neuronal differentiation ( .Fig, 46.-6 ). A
desmoplastic variant has been proposed for tumors in adults and may signify a different cell of origin.
Epidemiology and Risk Factors. Medulloblastomas are usually located infratentorially, accounting for approximately 2 percent of all CNS tumors in adults and 25 percent of intracranial tumors in children, second only to
Figure 46-6 Histopathological picture of a medulloblastoma, showing primitive, undifferential tumor cells with numerous neuroblastic (Homer-Wright) rosettes.
cerebellar astrocytomas. Although 50 percent of medulloblastomas are seen in children in the first decade of life, approximately 25 percent occur in patients over the age of 18. Tumors diagnosed in the seventh decade of life have been reported. There is a small second peak in incidence in patients 20 to 25 years of age. Interestingly, there seems to be a seasonal variation, with higher incidences in children born during the winter months and in those with congenital cerebral defects, possibly suggesting that these tumors are a remnant of embryonic dysfunction. Familial cases are known, including four cases in monozygotic twins, although there is no proven familial association. An association with leukemias and other CNS tumors, such as glioblastoma multiforme in first-degree relatives, has been noted.
Clinical Features and Associated Disorders. Patients often present with subtle problems that evolve over extended periods of time. In some patients, symptoms can exist for over 3 months before the tumor is diagnosed. The most common complaints include symptoms of increased intracranial pressure such as headache (especially in the morning) and vomiting. In younger children, behavioral changes such as decreases in activity or appetite may exist. Examination may demonstrate papilledema, truncal or limb ataxia, or nystagmus. A few patients have an increased head circumference or symptoms of leptomeningeal seeding similar to that seen in metastatic meningitis. There is a higher incidence of medulloblastoma in patients with nevoid basal cell syndrome, Turcot's syndrome, ataxia telangiectasia, and xeroderma pigmentosa.
Differential Diagnosis and Evaluation. The differential diagnosis for these tumors includes other primary CNS tumors such as ependymomas or gliomas, as discussed earlier, or metastatic tumors. Although CT scans are more readily available and may reveal evidence of hydrocephalus, all patients should undergo MRI with gadolinium. Occasionally, subarachnoid seeding is evident on initial imaging. CT or MRI scans usually demonstrate a hypodense mass with variable heterogeneous enhancement. Patients often present with evidence of obstructive hydrocephalus that requires immediate neurosurgical intervention such as shunting. Often conservative management with corticosteroids
allows surgical planning, and some reports suggest that shunting should not be performed if at all possible. Some believe that midline lesions are more commonly medulloblastomas whereas hemispheric lesions are more often astrocytomas, but histological confirmation is mandatory. Gross total resection of tumor should always be the goal.
Management. Once the diagnosis has been established, patients should receive craniospinal MRI with gadolinium enhancement to study the entire neuroaxis for tumor dissemination. This also allows examination of the resection bed without worry about postoperative enhancement caused by the surgery. If MRI of the spine is contraindicated, myelography can be performed. Patients should undergo cytological evaluation of cerebrospinal fluid at least 2 weeks after surgery. Although medulloblastomas have been known to spread outside the nervous system, especially to the bone and lungs, staging with bone marrow biopsy and imaging of the chest or radioactive bone scan should be performed only when such spread is clinically suggested. Reoperation should be considered at the time of tumor regrowth.
Patients have an increased risk of recurrence if gross total resection was not possible, if they are less than 4 years old, or if the tumor has a lateral location, evidence of cerebrospinal fluid dissemination, or a differentiated cellular histological appearance. Those patients younger than 18 months should undergo chemotherapy alone, whereas older patients should receive both radiotherapy and chemotherapy. Patients without the features just mentioned are considered to have a decreased risk of recurrence and can receive craniospinal irradiation and observation, with chemotherapy given only with evidence of recurrence.
Radiotherapy remains the mainstay of postsurgical treatment. Typically, craniospinal irradiation with increased doses to the tumor bed is performed because undetected tumor may be disseminated in the spinal cord. Recent advances in chemotherapy include the use of CCNU, carboplatin, and vincristine. y Treatment failure is usually evident at the original site alone; cerebrospinal dissemination may occur, or systemic involvement may be seen in a later stage. Almost half the patients show evidence of cerebral hemispheric involvement at recurrence. Refinements in radiotherapy may increase the incidence of systemic dissemination at relapse.y
Neurobehavioral abnormalities such as mutism, pseudobulbar affect, or derangements of eyelid opening have been documented in children undergoing posterior fossa tumor resection.y These usually resolve within months of surgery. Patients may have problems with cerebrospinal fluid drainage, requiring shunting. Children are at risk of decline in intellectual performance related to radiotherapy and possibly chemotherapy, especially if they are younger than 7 years old. Endocrinological problems resulting from pituitary failure, including delay of puberty, may be seen. Children who survive for a long time display decreases in perceptual motor tasks, manual dexterity, learning, and physical growth and development. y
Prognosis and Future Perspectives. Medulloblastoma seems to follow Collin's law that the risk of recurrence of tumor is highest during the period equal to the patient's age at diagnosis plus 9 months. y Survival is correlated with the extent of surgical resection for those over the age of 3 in whom dissemination is absent. y Five-year survival can occur in nearly 75 percent of patients who undergo high-dose craniospinal irradiation after gross total resection. Survival is poorer in patients younger than 5 years of age. Adults seem to have the same survival duration as children. y
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