Subependymomas

Subependymomas are indolent, slow-growing benign neoplasms originating from the subependymal glial matrix, consisting of a mixture of astrocytic, ependymal and transitional cell clusters surrounded by their fibers. They generally project into the ventricular lumen rather than into the brain parenchyma. Many are asymptomatic, found incidentally at autopsy. In contrast, spinal subependymomas arising in relation to the central canal of the spinal cord compress the cord substance early, invariably produce symptoms, and behave like other primary intrinsic neoplasms of the spinal cord. Likewise, tumors arising from the septum pellucidum, the region of the foramen of Monro or the aqueduct invariably produce symptoms, principally because of early occlusion of midline cerebrospinal fluid pathways. Others compress certain critical diencephalic structures, causing impairment of cognitive functions and memory. About one-fourth of the symptomatic intracranial tumors have mixed tumor cell populations, and consist of a mixture of ependymoma and subependymoma. The prognosis in such instances is much less favorable, approximating that of a pure ependymoma. The size of the neoplasm is another factor that affects the prognosis. Symptomatic tumors, regardless of their lo­cation. tend to be large. Although the neoplasm is known to occur in either sex, it is more common in men, and those harboring asymptomatic lesions tend to be older, in their seventh to ninth decades. The tumor has been reported in all decades of life; the mean age of occurrence of symptomatic tumors is 39 years, com­pared to 59 for asymptomatic lesions. To this date, subepen­dymomas have not been detected in children under 2 years of age.

Scheinker  is generally credited as being the first to report this neoplasm as a distinct entity (in 1945), although there are other earlier series of astrocytic and ependymal neoplasms, some of which contained tumors that can be classified as subependymomas by currently accepted histologic criteria. Fewer than 300 authentic cases have been reported to date, but increasing numbers of asymptomatic lesions are likely to be detected with the widespread use of computed tomography (CT) and magnetic resonance imaging (MRI).

Although the subependymoma is generally considered to be a neoplasm, there is some suggestive evidence to indicate that subependymomas may represent hamartomas from maldevelopment. Subependymomas of the fourth ventricle have been associated with heterotopic neuroglial tissue in the leptomeninges. There is also an isolated case report of subependymomas presenting at the same time in identical twins. Rubinstein considers that in some instances the lesions may be reactive in nature; he quotes one instance of chronic granular cryptococcal ependymitis and meningitis associated with subependymoma.

Pathology

The lesion originates immediately beneath the ependymal surface. As it grows. it almost invariably projects into the ventricular lumen, lifting the ependymal surface. Exceptionally, a subependymoma originating along the lateral ventricle may grow out into the brain parenchyma rather than into the ventricle, resembling a primary frontal lobe neoplasm.'? Typically, there is a well-defined demarcation between the deeper surface of the lesion and the adja­cent brain parenchyma. It does not have a true capsule. but it grows by expansion rather than infiltration. The surface of the mass is very smooth because it is covered by an ependymal lining. Larger lesions may be lobulated. The common sites of occurrence are the lateral ventricles, the septum pellucidum area, the foramen of Monro region, the third ventricle, the aqueduct and the fourth ventricle. In the fourth ventricle it may be attached to the floor, roof, or lateral recess or recesses. The distribution of the tumor in the various areas of the ventricular system is presumably related to the amount of subependymal glial matrix, which varies from region to region. The size of the neoplasm ranges from a few millimeters to several centimeters across. Although the tumor occurs as a single mass, as many as eight nodules have been recorded in a single patient. On occasion, the tumor arises concurrently with other primary neoplasms, such as glioblastoma or choroid plexus papilloma, but this is probably coincidental.

Attachment of the neoplasm to the underlying brain parenchyma through a broad base is the rule, but a few pedunculated subependymomas have been reported. The latter float free in the ventricular fluid, tethered to the ventricular wall through a narrow pedicle. Large masses may have multiple secondary sites of attachment to the ventricular surface; in such cases it may be difficult to ascertain the primary site of origin during surgical exploration.

The consistency varies from soft to rubbery, presumably depending upon the proportion of glial fibers within the lesion. The cut surface is smooth, with a very light tan color. Gross calcification and cystic changes have been observed. The tumor is generally avascular, hemorrhage within the lesion is exceptional. In rare instances, subarachnoid hemorrhage has been the presenting manifestation.

Obstructive ventriculomegaly is to be expected with subependymomas in certain strategic locations along the midline cerebrospinal fluid pathways. A lesion originating from the septum pellucidum may occlude one or both foramina of Monro, and a mesencephalic lesion, the aqueduct. A large fourth ventricular lesion may entirely fill that cavity. A tumor originating in the lateral recess of the fourth ventricle may extend out into the cerebello-pontine angle, erode the petrous bone and simulate a primary neoplasm in that location, such as an acoustic neurinoma or meningioma. A tumor arising from the roof or the floor of the fourth ventricle may encroach rostrally into the cerebral aqueduct or caudally into the cervical spinal canal.

Microscopically. the tumor typically consists of nests of glial cells separated by glial fibers. This characteristic appearance has led some pathologists to coin the term subependymal glomerate astrocytoma. Critical histologic studies have shown that some of the cells within these glomerate nests have attributes of ependymal cells (blepharoplasts, microvilli, cilia and characteristic junctional complexes) and others of astrocytes: still others are transitional between the two. Indeed, a peculiar type of primitive cell called the tanycyte, which has attributes of an ependymal cell in one pole and of a glial cell in the opposite pole, has been noted in ependymal neoplasms. These cells are normally found in the ependymal lining of lower mammals. Although the term subependymal mixed glioma is more accurate, the simpler alternative subependymomas is well established in the literature: it is doubtful that other terms will replace the latter.

Two unusual histologic variants have been reported recently. One is rhabdomyosarcomutous differentiation, the other is the presence of melanin pigment within the tumor cells. The tumor is sparsely cellular and mitotic figures are extremely rare. confirming the slow nature of tumor growth. The fibers between the cells stain positive for glial fibrillary acidic protein by the immunoperoxidase technique. Microcystic degeneration may occur within the glial fibrous matrix, giving it a spongy appearance. These microcysts may coalesce to form larger cyst. Variably scattered foci of calcification may appear within the glial matrix. Hemorrhage and hemosiderin deposition within the neoplasm are extremely rare.

The tumor in about 25 percent of individuals contains area, of cellular ependymoma. The latter areas show the features expected of classic ependymomas such as true or pseudoroettes, increased vascularity, frequent mitotic figures, area of necrosis and increased cellularity.

Symptoms and Signs

Headache and vomiting, an indication of raised intracranial pressure, are the most common initial presenting symptoms. Papilledema with transient obscurations of vision may be present in individuals with long-standing raised intracranial pressure. Ataxia in itself is a nonspecific sign. It may be related to ventriculomegaly with stretching of the corticospinal tract fibers, or it may he a sign of tumor arising from the floor of the fourth ventricle, especially if associated with vertiginous spells, vomiting, horizontal, vertical or rotary nystagmus, bilateral spasticity hyperactive reflexes and Babinski's sign. Lesions arising from the septum pellucidum can induce a personality disorders, impairment of recent and remote memory, episodes of transient loss of consciousness and generalized convulsions. Some may exhibit parkinsonian feature such as bradykinesia, heel rigidity and rhythmic tremor. Alteration of mood, apathy, and lack of initiative may suggest impairment of limbic structures. Diplopia and cranial nerve impairment are seen in brain stem lesions. In late or extreme obstructive hydrocephalus, patient, may present in coma with no focal localizing signs. Occasionally, an asymptomatic subependymoma is discovered by CT or MRI during the evaluation of a patient with an unrelated neurological disorder or unrelated symptoms.

Diagnostic Imaging

The majority of subependymomas are isodense with brain parenchyma on CT-scan without contrast administration or with contrast they generally not not enhance. Although diffuse and uniform enhancement has been reported with authentic subependymomas, intense diffuse enhancement associated with parenchymal edema should arouse suspicion (If a mixed ependymoma­subependymoma. Calcification and cystic changes within the tumor can be readily discerned on CT as hyperdense and hypodense areas, respectively. Rare instances- of hemorrhage into the tumor may be diagnosed as well.

MRI is a very helpful test, especially in instances where the tumor is isodense on CT -scan and dose not enhance with a contrast agent. The tumor outline appears as a hyperintense signal in T1 and T2-weighted images. Because these tumors are avascular, cerebral angiography is the least useful diagnostic test.

Therapy and Prognosis

Septum pellucidum lesions may be approached either through a transcallosal or a transfrontal, transventricular  route. Removal of the tumor is technically simple because of its avascularity. Fourth ventricular lesions ordinarily are exposed through a standard mid­line posterior fossa approach, with splitting of the vermis.

Tumors, attached to the floor of the fourth ventricle carry the worst prognosis, because  of the location. A mixed ependymoma­subependymoma carries a worse prognosis than a pure subependymoma. Recurrences do not occur unless the initial tumor resection is incomplete or the original tumor was a mixed tumor. Radiation therapy or other adjunctive therapies are unjustified in pure subependymomas.