Chordoid Meningioma: Differentiating a Rare World Health Organization Grade II Tumor from Other Meningioma Histologic Subtypes Using MRI.

BACKGROUND AND PURPOSE: Meningiomas are very commonly diagnosed intracranial primary neoplasms, of which the chordoid subtype is seldom encountered. Our aim was to retrospectively review preoperative MR imaging of intracranial chordoid meningiomas, a rare WHO grade II variant, in an effort to determine if there exist distinguishing MR imaging characteristics that can aid in differentiating this atypical variety from other meningioma subtypes. MATERIALS AND METHODS: Ten cases of WHO grade II chordoid meningioma were diagnosed at our institution over an 11-year span, 8 of which had preoperative MR imaging available for review and were included in our analysis. Chordoid meningioma MR imaging characteristics, including ADC values and normalized ADC ratios, were compared with those of 80 consecutive cases of WHO grade I meningioma, 21 consecutive cases of nonchordoid WHO grade II meningioma, and 1 case of WHO grade III meningioma. RESULTS: Preoperative MR imaging revealed no significant differences in size, location, signal characteristics, or contrast enhancement between chordoid meningiomas and other meningiomas. There were, however, clear differences in the ADC values and normalized ADC ratios, with a mean absolute ADC value of 1.62 ± 0.33 × 10(-3) mm(2)/s and a mean normalized ADC ratio of 2.22 ± 0.47 × 10(-3) mm(2)/s in chordoid meningiomas compared with mean ADC and normalized ADC values, respectively, of 0.88 ± 0.13 × 10(-3) mm(2)/s and 1.17 ± 0.16 × 10(-3) mm(2)/s in benign WHO grade I meningiomas, 0.84 ± 0.11 × 10(-3) mm(2)/s and 1.11 ± 0.15 × 10(-3) mm(2)/s in nonchordoid WHO grade II meningiomas, and 0.57 × 10(-3) mm(2)/s and 0.75 × 10(-3) mm(2)/s in the 1 WHO grade III meningioma. CONCLUSIONS: Chordoid meningiomas have statistically significant elevations of ADC and normalized ADC values when compared with all other WHO grade I, II, and III subtypes, which enables reliable preoperative prediction of this atypical histopathologic diagnosis.

Non-pituitary origin sellar tumours mimicking pituitary macroadenomas.

Although the large majority of sellar tumours are pituitary adenomas, several other pituitary and non-pituitary origin tumours arise in the sellar and parasellar regions. Given their location, non-adenomatous lesions frequently mimic pituitary macroadenomas and can pose a diagnostic challenge for the radiologist. Distinguishing rare sellar lesions from the common macroadenoma helps to direct the correct surgical approach and reduce the risk of incomplete resection and/or complications such as cerebrospinal fluid leak with the potential for meningitis. The purpose of this article is to review the imaging features of non-pituitary-origin sellar tumours, focusing on characteristics that may distinguish them from pituitary macroadenomas. Lesions include meningioma, metastatic disease, epidermoid cyst, germinoma, chondrosarcoma, giant cell tumour, and giant aneurysm.

RIP1 links inflammatory and growth factor signaling pathways by regulating expression of the EGFR.

There is considerable interest in understanding how inflammatory responses influence cell proliferation and cancer. In this study, we show that the receptor-interacting protein (RIP1), a critical mediator of inflammation and stress-induced NF-kappaB activation, regulates the expression of the epidermal growth factor receptor (EGFR). Mouse embryo fibroblasts (MEFs) derived from RIP1 knockout mice express very high levels of the EGFR. Reconstitution of RIP1(-/-) MEFs with RIP1 results in a lowering of EGFR levels. RIP1 influences EGFR at the mRNA level by regulating the EGFR promoter. Expression of RIP1 inhibits the EGFR promoter. RIP1 downregulates EGFR expression by interfering with the function of Sp1, which is a key activator of EGFR transcription. RIP1 suppresses Sp1 activity and overexpression of Sp1 reverses RIP1-mediated repression of the EGFR promoter. RIP1 is present both in the cytoplasm and in the nucleus. RIP1 coimmunoprecipitates with Sp1 in vivo and binds directly to Sp1 in vitro. A RIP1 mutant lacking the death domain fails to suppress Sp1 activity and the EGFR promoter, suggesting a critical role for the RIP1 death domain in EGFR regulation. Thus, our study identifies a new link between inflammatory and growth factor signaling pathways mediated by RIP1 and provides insight into the mechanism used by RIP1 to regulate EGFR levels.

Characterization of initiated cells in N-methylnitrosourea-induced carcinogenesis of the CNS in the adult rat.

Glial tumors may originate from the malignant transformation of multipotent glial progenitor cells, but tools to study malignant transformation leading to gliomas are limited by the lack of biological systems that represent early stages of this disease in adult animals. In order to characterize the initiated cells that give rise to gliomas, we have employed the N-methylnitrosourea (MNU) model for induction of brain tumors in adult rats (Rushing et al., 1998). Specifically, we have isolated and cultured transformed (premalignant) cells from normal-appearing brains of rats exposed to MNU for 10 weeks and from histologically abnormal brains of rats exposed to MNU for 15 weeks. We compared them with cells cultured from control animals under identical conditions. Cultured cells were classified according to their morphology, immunophenotype, karyotype, proliferation capacity, and tumorigenicity in athymic mice. Cultures from untreated normal rat brains grew as monolayers and had normal karyotypes (42 X,Y), epithelioid morphology, and slow proliferative capacity (doubling time > 120 h). In contrast, cultured cells from brains of MNU-exposed animals had karyotypes that ranged from normal to highly aneuploid. Aneuploid lines grew rapidly in multilayers (doubling time < 24 h), had differentiated astrocytic or oligodendroglial morphology and immunohistochemical staining profile, and yielded tumors in athymic mice. Initiated cells with minor chromosomal aberrations assumed mixed bipolar or tripolar morphologies in high density cultures, proliferated rapidly, but showed contact inhibition and failed to induce tumors when injected s.c. in athymic mice. In general, lines showing no evidence of chromosomal aberrations had the most epithelioid morphology, proliferated slowly (doubling time > 72 h), and retained strict contact growth inhibition. The presumed undifferentiated glial progenitor cells in culture from either control or MNU-treated rats variably expressed markers such as vimentin, nestin, and NG2 proteoglycan, and they weakly expressed the mature astrocytic or oligodendroglial markers glial fibrillary acidic protein or galactocerbroside, respectively. These cultures differentiated to bipolar-tripolar morphology with concomitant maturation to a GFAP+ or GalC+ phenotype upon exposure to secondary messengers such as dibutyryl-cyclic-AMP and/or growth factors such as basic fibrillary growth factor. Continuous stimulation with these messengers resulted in terminal differentiation and consequent death upon withdrawal of the stimulus. These results provide information that could lead to detailed characterization of initiated, premalignant cells in the adult brain and to a better understanding of glial carcinogenesis.

Radiation change versus recurrent astrocytoma: diagnostic utility of the proliferation index?

Differentiation of recurrent glioma from radiation damage can be a challenge to neurologists, neurosurgeons, neuroradiologists, and even neuropathologists. We hypothesized that by evaluating sections of recurrent lesions with proliferation markers we might objectively differentiate between radiation damage gliosis and recurrent astrocytoma. We compared the labeling indices of radiation damage and recurrent neoplasm immunohistochemically, using an antibody to MIB-1, a monoclonal antibody to the Ki-67 proliferation marker. Five of the six recurrent neoplasms were gliomas; four these were astrocytic tumors. In most cases, the MIB-1 LI of radiation damage was < 1% and the LI of recurrent neoplasm was > 3%, with pertinent exceptions. We discuss our findings and their possible interpretation.

Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype.

In this study, we report our results on the proliferative activity of ependymomas as determined by MIB-1 (also known as Ki-67) immunohistochemical analysis, and we compare our results with those obtained by immunolabeling with monoclonal antibodies to p53 and bcl-2 proteins to assess whether expression correlated with ependymoma subtype or tumor grade. The study included 4 myxopapillary ependymomas (Grade I of the World Health Organization [WHO] scale), 10 subependymomas (WHO Grade I), 17 ependymomas (WHO Grade II), 2 papillary ependymomas (WHO grade II), and 4 anaplastic ependymomas (WHO Grade III). The MIB-1 proliferation index was significantly higher in tumors diagnosed as anaplastic ependymoma (P < .001), with a moderate level of correlation (Kendall's tau-b = 0.557, asymptotic standard error = 108). In addition, one ependymoma (WHO Grade II) not considered overtly anaplastic by routine histologic criteria showed a high MIB-1 labeling index, suggesting that the MIB-1 proliferation index might be a more objective indicator of tumor grade. The remaining WHO Grade I and Grade II ependymomas showed low proliferative activity. bcl-2 oncoprotein expression was identified in all of the four myxopapillary and in both papillary ependymomas. An additional observation was the correlation of p53 expression with increasing WHO grade. These data suggest that high MIB-1 and p53 immunolabeling might be objective indicators of high grade in ependymomas that do not otherwise meet routine histologic criteria for high-grade ependymoma. Subsequent clinicopathologic analyses will be important in assessing whether these markers are useful as independent predictors of survival.

Therapeutic dilemma of disseminated CNS germinoma and the potential of increased platinum-based chemotherapy delivery with osmotic blood-brain barrier disruption.

In contrast to disseminated extraneural germinoma, systemic chemotherapy in disseminated central nervous system germinoma often results in only transient responses. After surgery, cytoreduction was accomplished with systemic multiagent platinum-based chemotherapy in 4 consecutive patients known to have a poor prognosis, due to central nervous system germinoma at more than one anatomic site. When tumor enhancement resolved (i.e., blood-brain barrier integrity was restored), intensive consolidation therapy with carboplatin and etoposide was given in association with mannitol-induced osmotic blood-brain barrier disruption. Complete responses occurred in all 4 patients and currently 3 are tumor-free without radiotherapy 24-40 months from diagnosis, suggesting the importance of increased drug delivery for an extended period.

Asymmetric pneumatization of the petrous apex.

Three patients with high-intensity MR signals from one petrous apex, but nonpathologic fine-cut computed tomography are reported. In two of the three patients, normal bone marrow within the petrous apex on one side is believed to have generated the high-intensity signal. In one of the three patients, the etiology of the MR image remains obscure, but may represent the earliest stages of petrous cholesterol granuloma or mucocele. We have reviewed 500 head CT scans performed for non-otologic reasons, in an attempt to establish the frequency of this finding. The literature on MR and CT imaging of the petrous apex and asymmetric pneumatization of the petrous apex is reviewed.

Spinal fluid profile following surgery in the subarachnoid space.

Neurotologic and skull base procedures that include dissection within the subarachnoid space carry with them the potential for meningitis. Postoperative aseptic leptomeningitis occurs more frequently than purulent bacterial meningitis. Differentiation between these two conditions early in the postoperative period is important to avoid delay in or unnecessary treatment. The definitive diagnosis is made with cerebral spinal fluid culture. Early differentiation between postoperative aseptic leptomeningitis and purulent bacterial meningitis on the basis of results of cerebral spinal fluid profile before cerebral spinal fluid culture would result in earlier appropriate therapy.

Surgical management of nasopharyngeal angiofibroma involving the cavernous sinus.

Involvement of the cavernous sinus by juvenile nasopharyngeal angiofibroma represents a therapeutic challenge. We present our experience over the past 5 years with the surgical management of six cases of juvenile nasopharyngeal angiofibroma involving this site. Three of six patients had involvement of the medial aspect of the cavernous sinus and tumor was removed using a midline extracranial approach. Of three remaining patients, two had invasion of the medial and inferior margin of the cavernous sinus and one represented a recurrent lesion. The tumor in these three cases was resected using a combined frontotemporal and lateral infratemporal fossa approach. An extracranial recurrence occurred in one patient, and the remaining five patients have had no evidence of recurrent disease 12 to 71 months following surgery. Morbidity has been limited to trismus, facial hypesthesia, and serous otitis media.

Magnetic resonance imaging in the diagnosis of temporal bone and skull base lesions.

Six patients are presented in whom total reliance on magnetic resonance imaging (MRI) interpretations would have resulted in less than ideal treatment. The misleading information on magnetic resonance imaging could be divided into two types; as follow: type I were those in which there was no signal but nonosseous pathology was present, and in type II an abnormal signal was present but misinterpreted. In three of these patients (cases, 2, 3, and 5), information gained from more traditional means (history, physical examination, audiologic and vestibular testing, and computed tomography) led to proper treatment, whereas, in two patients (cases 4 and 6), treatment exceeded that required by the disease process. In one patient (case 1), ideal therapy resulted, despite a negative magnetic resonance imaging study, when a small intracanalicular tumor was found fortuitously during a translabyrinthine vestibular nerve section for vertigo. Although magnetic resonance imaging provides excellent supplemental information to more traditional means of diagnosis, it cannot be used entirely in their place. As gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) becomes more readily available, as the resolution of magnetic resonance imaging improves, and as we gain more familiarity with this diagnostic modality, misleading information from these studies should decrease.

Vascular decompression of the cochlear nerve in tinnitus sufferers.

An estimated 40 million Americans suffer from tinnitus, and approximately 20% of these sufferers feel that the quality of their life is significantly impaired by this symptom. Despite thorough evaluation, the underlying etiology in the majority of these patients remains obscure or conjectural. Most of these patients will, however, benefit from consultation and avoidance of caffeine, nicotine, and salt, while others require biofeedback, amplification, masking, and even psychotherapy. On rare occasions, physicians are presented with a patient complaining of unilateral tinnitus of undetermined etiology who, in spite of a thorough evaluation and all conventional therapies, continues to be severely handicapped by that symptom. Early findings suggest that these patients may be suffering from vascular loop compression of the cochlear division of the eighth cranial nerve. When patients are carefully selected, retrosigmoid decompression of that vascular loop has provided gratifying relief.

The surgical management of epidural mucoceles.

Mucoceles of the paranasal sinuses extending into the epidural space are both uncommon and difficult to surgically manage. To best overcome the problem of recurrent disease, we have adopted a combined otorhinolaryngologic-neurosurgical approach which emphasizes removal of as much as possible of the mucocele and marsupialization, or permanent drainage, of the disease site into the nasal cavity. Recently, we have modified this procedure in selected cases to include resection of involved dura and isolation of the epidural space from the nasal cavity. The indications and results of both forms of management are now reported in ten patients.

Axial subcutaneous scalp flaps in the reconstruction of the anterior cranial fossa.

A major concern following combined craniofacial resection of neoplasms involving the floor of the anterior cranial fossa is the creation of a watertight separation between the contents of the anterior cranial fossa and the upper aerodigestive tract. The reconstructive technique should satisfy several goals, which we will outline. The axial subcutaneous scalp flap meets these goals and has proved to be useful in reconstruction of the anterior skull base. We used the axial subcutaneous scalp flap for this purpose in three patients. Herein, we report our experience and emphasize the importance of the vascular pattern of the anterior scalp.

Resection of upper aerodigestive tract tumors involving the middle cranial fossa.

Benign and malignant neoplasms of the upper aerodigestive tract that invade the middle cranial fossa are frequently considered unresectable due to the proximity of the cavernous sinus and internal artery, and to the inaccessibility of this region via conventional surgical approaches. We report our experience using a combined, lateral intracranial and infratemporal fossa procedure for the management of these tumors in four patients. Successful removal of neoplasm associated with minimal morbidity was accomplished in 3 patients, 2 with angiofibromas and 1 with an adenoid cystic carcinoma. The postoperative course of the fourth patient was complicated by meningitis which resulted in the patient's death five months following resection of an adenocarcinoma.

Neurosurgical applications of the cyanoacrylate adhesives.

The cyanoacrylate adhesives are a biologically heterogenous group, some of which are potentially valuable additions to the neurosurgical armamentarium. The commercially available cyanoacrylates usually contain the more toxic methyl and ethyl monomers. The safe butyl monomer, isobutyl 2-cyanoacrylate, is approved in the United States by the Food and Drug Administration for investigational use only. Isobutyl 2-cyanoacrylate may prove to be useful for the extravascular reinforcement of intracranial aneurysms and for the intravascular occlusion of carotid-cavernous fistulae. Safe and effective alternatives exist for the management of these two problems. The sealing of certain cerebrospinal fluid fistulae and the intravascular occlusion of certain arteriovenous malformations may be more effectively accomplished with isobutyl 2-cyanoacrylate than with other currently available techniques. The ultimate role of this and of other as yet untested cyanoacrylates in neurosurgery remains to be determined.