Faculty Bibliography

Meningiomas are the second most common tumor to involve the cerebellopontine angle (CPA), but controversy exists as to whether they can arise within the internal auditory canal (IAC) or whether involvement of the IAC occurs secondarily by extension from the CPA. This paper reports on a patient with an enhancing IAC meningioma that then grew and on subsequent scans was found to involve the CPA. This case demonstrates that these tumors can arise within the IAC and can grow out to involve the CPA. These findings are discussed within the context of meningioma tumor genetics and the histologic evidence for precursor cells in the IAC. The radiologic findings useful in distinguishing an acoustic neuroma from a meningioma are reviewed in the light of this case. While an enhancing mass projecting into the IAC is most often an acoustic neuroma, this radiologic findings is not pathognomonic

Calcification, as a feature of the vasculopathy, is a common pathological finding in children with acquired immunodeficiency syndrome. Large and small blood vessels of many organs including brain, heart, lungs, kidneys, liver, and spleen are affected. We report a case with calcification in multiple organs that was most prominent in the cardiac and skeletal muscle cells and the blood vessels of the cerebrum. To our knowledge, calcification of this degree has not been documented previously in a human immunodeficiency virus-infected child

OBJECTIVE AND IMPORTANCE: Although the differential diagnosis of intracranial lesions in patients who have tested positive for human immunodeficiency virus is extensive, toxoplasmosis, lymphoma, and progressive multifocal leukoencephalopathy comprise approximately 90% of such cases. Cytomegalovirus infection of the central nervous system may be difficult to diagnose and rarely presents as mass lesions revealed by radiographic studies. CLINICAL PRESENTATION: Two patients who had tested positive for human immunodeficiency virus presented with progressive focal neurological deficits. Radiographic studies revealed solitary contrast-enhancing lesions in the right basal ganglia and right cerebellar hemisphere, respectively. INTERVENTION: The first patient underwent a stereotactic biopsy but died despite appropriate therapy. The second patient died without tissue having been obtained for diagnosis. Postmortem examinations revealed necrotizing lesions with diffuse areas of infiltrating histiocytes containing eosinophilic cytomegalovirus inclusion bodies. CONCLUSION: Although rare, cytomegalovirus infection should be considered in patients who have tested positive for human immunodeficiency virus and who present with enhancing intracranial lesions

OBJECTIVE AND IMPORTANCE: Intracerebral schwannomas not associated with cranial nerves account for less than 1% of surgically treated schwannomas of the central and peripheral nervous system. Subfrontal schwannomas are extremely rare, with only 15 cases reported to date. CLINICAL PRESENTATION: A 33-year-old man presented with a 4-month history of progressive headaches and lethargy. Radiographic studies revealed a large subfrontal tumor thought to be a meningioma preoperatively. INTERVENTION: The patient underwent a craniotomy for resection of his tumor. Intraoperatively, a large extra-axial tumor arising from the floor of the left frontal fossa was encountered. CONCLUSION: Microscopic examination of the tumor revealed a schwannoma. Several theories on the possible origin of intracerebral schwannomas have been considered. Because of the age of the patient at presentation, many authors have postulated a developmental origin for these lesions. However, extra-axial schwannomas not associated with cranial nerves often present later in life, suggesting a different pathogenesis for this subgroup

Ependymomas are rare central nervous system (CNS) neoplasms that occasionally disseminate along the neuraxis or to extraneural sites. Definitive criteria predictive of dissemination have yet to be determined. One hundred forty patients with CNS ependymoma (88 primary spinal and 52 primary intracranial tumors) were surgically treated by the senior author (F.J.E.) between 1986 and 1994. Sixteen patients (11.4%) demonstrated tumor dissemination. The disseminated group consisted of 11 (12.5%) of 88 primary spinal and five (9.6%) of 52 primary intracranial ependymomas. The authors retrospectively reviewed the patients with CNS ependymoma and have identified several characteristics associated with dissemination from the primary tumor site. The mean time from diagnosis to dissemination was 6.8 years. The patients with disseminated disease were younger (16.8 vs. 28.3 years old, p = 0.02), had fewer gross-total resections (29% vs. 68%, p = 0.015), and had tumors with higher proliferative indices (MIB-1 staining, 13.14% vs. 2.06%, p = 0.02). High-grade tumors had a mean proliferation index of 21%, versus 2.4% and 1.6% for myxopapillary and low-grade tumors, respectively (p = 0.0003). In contrast to previous studies, tumor histology was the most significant variable for time to dissemination as determined by multivariate analysis (p = 0.008). Myxopapillary and high-grade tumors were 3.6 and 5.6 times more likely to have a shorter time to dissemination than low-grade tumors. In addition, dissemination is associated with a worse prognosis. At follow-up review, 31% of patients with disseminated disease had died compared to 7% of patients without dissemination (p = 0.04). It is concluded that younger patients with subtotal resections, myxopapillary or high-grade histology, and tumors with high proliferative indices are at substantial risk for the development of disseminated disease during their clinical course

An important contributor to the malignancy of brain tumors is their ability to infiltrate the brain. Extracellular matrix molecules and cell adhesion molecules on cell surfaces play key roles in cell migration. In the present study, we used reaggregates of dissociated cells from freshly excised human brain tumors to analyze the migration of cells from human brain tumors of different types and grades on many different adhesion proteins adsorbed to glass substrates. Proteins were chosen based on their presence in normal or neoplastic nervous tissue, and included the extra-cellular matrix molecules fibronectin, collagens, fibrinogen, laminin, tenascin-C, thrombospondin, and the neuron-glia cell adhesion molecule, Ng-CAM. Cells from astrocytomas (n = 24) migrated on a variety of substrates, in contrast to cells from primitive neuroectodermal tumors cells (n=6), which only migrated well on laminin, fibronectin, or type IV collagen but not on the other substrates. Typically, migrating cells from astrocytomas of all grades had long, slender processes, were usually bipolar, and their cell bodies did not spread well on any substrate. Although there was variability in the migration of cells from astrocytomas of the same grade, cells from high-grade astrocytomas tended to migrate more extensively (42.3 +/- 4.7 micrometers/16 h: n = 16) than cells from lower grade astrocytomas (28.9 +/- 3.9 micrometers/16 h; P = 0.07; n = 8); the most striking differences were observed for collagen substrates, on which cells from lower grade astrocytomas migrated at very low levels (7.6 +/- 2 .6 micrometers/16 h) and cells from high-grade astrocytomas at higher levels (24.4 +/- 5.2 micrometers;P = 0.01). In contrast to primary cells from glioblastomas (n = 13), glioblastoma cell lines (n = 10) consistently spread on various substrates and migrated at high levels (69.5 +/- 7.6 versus 46.4 +/-5.7 micrometers/16 h; P = 0.03), in particular, on collagens (108.4 +/- 20.2 versus 28.0 +/- 6.1 micrometers/16 h; P= 0.001). Specific monoclonal antibodies to alphaV and beta1 integrin monomers completely inhibited the migration of astrocytoma cells on most substrates, suggesting that alphaV and beta1 integrins play a crucial role in brain tumor infiltration. These studies also suggest that although a large number of extracellular matrix molecules may promote tumor cell migration, disrupting the function of only a few tumor cell receptors may be critical for tumor infiltration in the brain

A consecutive series of six patients underwent operative resection of intramedullary spinal cord subependymomas between January 1981 and August 1993. Three men and three women between the ages of 26 and 66 years experienced symptoms for a mean of 50 months preceding diagnosis. The locations of the tumors were predominantly cervical or cervicothoracic, except in one patient. At operation, a complete extirpation was achieved in each patient. No patient received further adjunct therapy. There has been no tumor recurrence in any patient after a mean follow-up period of 39 months. Most of the intramedullary spinal cord tumors are either ependymomas or astrocytomas. Clinical histories, physical examinations, and radiographic investigations are not conclusive for absolute diagnosis of subependymomas; however, intraoperative gross observations have shown these well-demarcated tumors to be located eccentrically within the spinal cord. Pathological examinations demonstrate tumors with sparse cellularity, clustering of cells, and dense fibrillary stroma. Proliferation studies with the mouse monoclonal antibody MIB-1 reconfirm the slow growth potential of these benign tumors

The expression of the extracellular matrix glycoprotein tenascin-C (TN) is enhanced in human astrocytomas and correlates with angiogenesis. To determine whether vascular cells are able to synthesize TN, we investigated the expression of TN protein and mRNA in nine astrocytomas. Immunogold electron microscopy in two glioblastomas multiforme detected the presence of TN in an extracellular perivascular location and to a lesser extent among tumor cells, confirming light microscopy immunohistochemical findings. In situ hybridization of astrocytomas using a digoxigenin-labeled antisense riboprobe detected strong staining for TN mRNA in vascular cells, especially in hyperplastic vessels, including those at the invasive edge of the tumors but not in vessels of normal brains. We observed weaker staining in tumor cells indicating a higher level of TN mRNA in vascular than in tumor cells. No staining was detected with the sense probe. Moreover, we investigated the ability of human brain microvessel endothelial cells (HBMECs) in primary culture to synthesize TN in vitro. Western blot analysis of the culture supernatants from HBMECs detected large amounts of TN. Immunogold silver staining demonstrated the presence of TN on the surface of HBMECs and in the subendothelial matrix. The distribution of TN mRNA in vascular cells of astrocytomas and the ability of HBMECs to synthesize TN in vitro demonstrate that vascular cells, including endothelial cells, are a major source of TN associated with angiogenesis. Furthermore, our results suggest that TN expression may be associated with endothelial cell activation and may play an important role in angiogenesis