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Tumors of the Brain Stem, Cerebellum, and Fourth Ventricle

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Tumors of the Brain Stem, Cerebellum, and Fourth Ventricle 3601_e06_p171-192 2/15/02 4:32 PM Page 171 6 Tumors Of The Brain Stem, Cerebellum, and Fourth Ventricle ROGER J. PACKER, HENRY S. FRIEDMAN, LARRY E. KUN, AND GREGORY N. FULLER The posterior fossa is a small region of brain cradled in the posterior fossa than those in adults. Ependy- on all sides by bone and limited above by the tento- momas, which are more frequent in a supratentorial rium. The brain stem, cerebellum, and fourth ventri- region in adulthood, are more frequently found in the cle occupy this region of brain. Expansion of a mass posterior fossa in childhood. in this infratentorial area occurs at the expense of the With the modern neuroimaging techniques, which normal structures in the region and may result in have replaced previously used tests such as pneu- brain stem or cerebellar dysfunction, often associated moencephalography and angiography, these tumors with blockage of the fourth ventricle and hydro- can now be diagnosed at earlier stages of disease. cephalus. Although many different tumor types may Computed tomography (CT) delineates the presence arise in the posterior fossa and affect the brain stem, of tumor in greater than 95% of patients with poste- cerebellum, and fourth ventricle, the majority are rior fossa tumors, but, due to bone artifact obfusca- either medulloblastomas, cerebellar astrocytomas tion, this technique has limited applicability. For le- (rarely, higher grade cerebellar glial tumors), brain sions that arise deep within the posterior fossa, stem gliomas, or ependymomas. Other tumor types, especially those at the cervicomedullary junction, and which may arise less frequently, include choroid for lesions that infiltrate the brain stem, magnetic res- plexus papillomas, germ cell tumors, and dermoid onance imaging (MRI) has become the procedure of lesions. Because tumors do not respect discrete com- choice. The beauty of MRI is that it allows scanning partmental landmarks, those that arise in the thala- in all planes without reformatting, which makes it eas- mus or suprasellar region can extend inferiorly into ier to anatomically define a lesion in the brain stem the posterior fossa. Similarly, lesions that arise from or deep in the cerebellum. The extent of the infil- the spinal cord can extend up into the medullary area trating component of posterior fossa tumors, espe- and cause symptoms of brain stem dysfunction. cially those that infiltrate the brain stem, are visual- Fewer than 5% of all adult tumors originate in the ized considerably better with MRI than with CT. posterior fossa, whereas approximately 50% of pri- The clinical presentation associated with posterior mary central nervous system (CNS) tumors occurring fossa tumors is essentially similar in adults and chil- in patients younger than 15 years of age arise in the dren. In general, the briefer the history, the more fourth ventricular region. For unclear reasons, lower likely the tumor is to be growing rapidly and arising grade lesions in children are more frequently found in the axial midline of the posterior fossa, obstruct- 171 3601_e06_p171-192 2/15/02 4:32 PM Page 172 172 PRIMARY CENTRAL NERVOUS SYSTEM TUMORS ing cerebrospinal fluid (CSF) flow. Late in the course SPECIFIC TUMORS of illness, symptoms usually include increased in- tracranial pressure, focal neurologic deficits sec- Medulloblastoma ondary to compromise of brain stem or cerebellar tissue, and meningeal irritation, whereas early in the Medulloblastomas are common tumors of childhood course of illness nonspecific complaints of vague, in- in the posterior fossa. They typically arise in the ver- termittent headache, fatigue, and personality change mis but can arise in the cerebellar hemisphere (Fig. may predominate. The clinical triad of increased 6–1). Medulloblastomas are classic “small round intracranial pressure—headache, vomiting, and blue cell” tumors in which neoplastic cells may ex- blurred or double vision—is the hallmark of an in- hibit various organizational patterns, including un- fratentorial tumor. Although a classic headache of in- structured sheets, nests, and cords. Four named mor- creased intracranial pressure is common late in the phologic variants are recognized by the current WHO disease, early on the headache may be far less spe- classification: classic medulloblastoma, desmoplastic cific. Similarly, vomiting, which occurs in the morn- medulloblastoma, medulloblastoma with extensive ing and is associated with relief of head pain, is a nodularity and advanced neuronal differentiation, and footprint of posterior fossa tumors that have ob- large cell medulloblastoma. In addition, there are two structed the fourth ventricle. Less frequently, vomit- very rare related neoplasms: melanotic medulloblas- ing may occur secondary to tumors that invade or toma and medullomyoblastoma (medulloblastoma compress the floor of the fourth ventricle, especially with skeletal muscle differentiation). All medul- in the medullary area. The vomiting pattern from such loblastoma variants are malignant neoplasms in lesions is usually more constant during the day and which mitotic figures are typically numerous and ne- is associated with persistent nausea, anorexia, and crosis is often present. Rapid growth with secondary significant weight loss. involvement of the fourth ventricle and seeding via Cerebellar deficits occur in most patients with pos- CSF pathways is common. terior fossa tumors. In midline lesions, compromise The desmoplastic medulloblastoma, a histologic of the anterior and posterior lobes of the cerebellum variant of the medulloblastoma, received its name causes truncal and gait ataxia manifested by un- from the abundance of connective tissue present, steadiness when sitting and a staggering gait. Limb which can be seen particularly well with reticulin or ataxia occurs more frequently in lesions that involve Masson trichrome stains. The distinctive appearance the lateral cerebellar hemispheres, most commonly of this tumor derives from the contrast of background cerebellar astrocytomas. However, brain stem lesions with scattered circumscribed areas that lack a con- that infiltrate the cerebellar peduncles will frequently nective tissue stroma, so-called “pale islands” (Fig. cause cerebellar symptomatology. 6–2). Such foci often exhibit glial or neuronal dif- Other focal neurologic deficits may occur in pa- ferentiation demonstrated by immunopositivity for tients with posterior symptoms. Ocular motor deficits glial fibrillary acidic protein or synaptophysin, re- are relatively frequent and tend to be of localizing spectively. The prognostic significance of the desmo- value, except for a sixth nerve palsy, which may be plastic variant and glial/neuronal differentiation is not present secondary to diffuse increased intracranial yet known. pressure. Epileptic seizures rarely occur in children In addition to medulloblastoma, another entity in or adults with subtentorial tumors except in patients the differential diagnosis of a malignant neoplasm with infiltrating masses that extend into the subcorti- arising in the cerebellum of a young child is atypical cal areas and in patients with lesions that have dis- teratoid/rhabdoid tumor (ATRT). These neoplasms seminated into the nervous system. Alterations in con- can resemble medulloblastoma, particularly the large sciousness may occur, but tend to be a late finding. cell medulloblastoma variant. In general ATRTs are Acute hemorrhage into a posterior fossa tumor may more heterogeneous and pleomorphic than medul- result in acute coma. loblastomas and their immunophenotypic profile is Infants and young children with posterior fossa distinctive: All are immunopositive for vimentin, the tumors are notoriously difficult to diagnose, although vast majority (95%) are positive for epithelial mem- they may have increasing head circumference due to brane antigen (EMA), and a large percentage (60% their open sutures and fontanelles. to 75%) show positivity for smooth muscle antigen. 3601_e06_p171-192 2/15/02 4:32 PM Page 173 Tumors of the Brain Stem, Cerebellum, and Fourth Ventricle 173 Figure 6–1. Medulloblastoma visible in vermis at time of surgery. Note herniation of cerebellar tonsils. In addition to these markers, a wide range of other antigens may be expressed, including epithelial (ker- atins) and neural (GFAP, synaptophysin) markers (Kleihues and Cavenee, 2000). ATRTs are aggressive tumors with a tendency for widespread dissemination via cerebrospinal pathways. Presentation Patients with medulloblastoma typically present with vomiting, headache, and an ataxic gait (Cushing, 1930). Manifestations of obstruction of the fourth ventricular outlet include vomiting, headache, Figure 6–2. Desmoplastic medulloblastoma. Like all medul- lethargy, and occasionally papilledema. Vomiting sec- loblastomas, this variant is composed of small neoplastic cells with hyperchromatic nuclei and scant cytoplasm. In desmo- ondary to a medulloblastoma usually occurs when the plastic medulloblastomas, there is an abundant reticulin child awakens in the morning and may precede res- stroma throughout the tumor, except in scattered, roughly olution of complaints for the remainder of the day. spherical, aggregates termed “pale islands,” thus imparting a Progressive awkwardness and clumsiness, with diffi- distinctive architectural pattern. culty standing or walking alone, results from in- 3601_e06_p171-192 2/15/02 4:32 PM Page 174 174 PRIMARY CENTRAL NERVOUS SYSTEM TUMORS Table 6–1. Staging of Patients with Medulloblastoma Average Risk
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