Correlation of tumor plasminogen activator with peritumoral cerebral edema. A CT and biochemical study

Extracts from 15 human cerebral tumors were tested by a fibrin-plate plasminogen-dependent assay for levels of tumor plasminogen activator (TPA) activity. The TPA activity was correlated with the amount of perineoplastic edema as quantified on computerized tomography (CT) brain scanning. Analysis of the results showed a correlation coefficient of 0.72 when all tumors were included. Analysis of the nine tumors with the highest TPA levels showed a correlation coefficient of 0.96. One metastatic tumor had the highest level of TPA activity, equivalent to a pure 100-micrograms/ml solution of urokinase, and the greatest amount of cerebral edema on CT. Meningiomas generally had the next highest levels of TPA activity and edema, followed by astrocytomas of varying grades, which generally had the lowest level of TPA activity. However, three astrocytomas that had low TPA activity also had significant edema surrounding the tumor, indicating that more than one mechanism may be producing peritumoral edema. There was no correlation between tumor size and the amount of perineoplastic edema. These preliminary results suggest that TPA's may be involved in the production of perineoplastic cerebral edema and that treatment of patients with currently available plasminogen activator inhibitors may be successful in reducing peritumoral edema.     

A case of multiple meningiomas: two lesions have different clinicopathological features, respectively

A 60-year-old man presented with general convulsion. Computed tomographic (CT) scans and magnetic resonance (MR) imaging showed two meningiomas located at the bilateral frontal convex respectively. In spite of the similar tumor size, the left tumor only had marked peritumoral edema. Angiography showed that the left lesion was more amply supplied from the internal carotid artery than the right one was. These two tumors were totally resected. The left tumor adhered to the surrounding brain tissue more intensely than the right one. Both tumors were microscopically diagnosed as angiomatous meningioma. The left tumor cells have a stronger immunopositivity for VEGF than the right ones. We suggest that pial-blood supply, adhesion to brain tissue and VEGF expression influence the development of meningioma-associated peritumoral edema.     

Relationship between flow cytometric features and clinical behavior of meningiomas

Meningiomas have a wide range of biological potential and clinical behavior. Histological findings are helpful in recognizing the malignant potential of a given tumor, but often fail to correlate with gross features, liability of recurrence, and extent of associated cerebral edema. To find alternate approaches to improve the correlation between biological and clinical behavior, 20 meningiomas were studied by flow cytometry (FC), an assessment that has been applied to meningiomas previously. Such FC features as DNA index (DI) and proliferative index (PI, %G2 + %S) were correlated with size, location, brain invasion, associated edema, and recurrence. Tumors with severe edema had significantly higher PIs (19.5 +/- 4.1) than those with moderate (12.6 +/- 4.5) or minimal (8 +/- 0) edema (P less than 0.05). The PI was greater than 16 in those tumors that recurred (n = 3) or invaded the brain (n = 3). Six tumors were aneuploid (DI, 1.33 +/- 0.17; PI, 17.1 +/- 5.3). These were uniformly large when compared with the diploid tumors, which were more variable in size. All of the aneuploid tumors were associated with moderate to severe cerebral edema. Two partly psammomatous tumors with high PIs and foci of high cellularity suggesting recent growth were associated with severe edema. One of these exhibited brain invasion. These preliminary data indicate that FC may have a potential use in the clinical management of meningiomas.     

Stereotactic radiosurgery for acoustic tumors.

Stereotactic radiosurgery is an important alternative treatment for carefully selected patients with acoustic tumors. We perform radiosurgery under local anesthesia, and 91% of our patients have been discharged from the hospital within 24 hours after treatment. All returned to their preoperative level of function or employment within 5 to 7 days after treatment. Our current tumor control rate is 97%, but reduction in tumor size, judged by strict, objective criteria, was achieved in only 23%. Our actuarial rate of useful hearing preservation after radiosurgery is 38% at 1 year. Three tumors increased in size after treatment. Only one of the three demonstrated increased mass effect on surrounding brain structures by neuroimaging criteria. No increase has led to worsened clinical symptoms or has required surgical excision at this point in follow-up. The 1-year rates for developing new facial or trigeminal neuropathies after radiosurgery were 30% and 33%, respectively. Cranial neuropathies had a delayed onset, with the median onset occurring after 5 to 6 months. The vast majority were partial at onset, and most improved over time. Communicating hydrocephalus requiring ventriculoperitoneal shunts developed after radiosurgery in four patients. Eight patients developed increased signal within adjacent brain parenchyma on T2-weighted MR imaging, consistent with edema or blood-brain barrier breakdown. It is unlikely that stereotactic radiosurgery using the gamma knife will obviate the need for microsurgical removal performed by skilled and experienced microsurgeons. However, radiosurgery is a safe and effective treatment for patients whose medical problems make surgery unacceptably dangerous, those with bilateral tumors or a tumor in their only hearing ear, those who have recurrent tumor despite surgical resection, or patients who refuse microsurgical excision.     

Lipomatous meningioma: report of 2 cases and review of the literature

BACKGROUND: Lipomatous meningioma is a rare but, most of the time, benign tumor. Its pathogenesis is still debated: it is usually considered to be part of the metaplastic meningioma, but several authors recently suggested that fat accumulation inside the tumor was related to metabolic disorders of the meningothelial cells. CASES DESCRIPTION: We report 2 cases of lipomatous meningioma. Both patients were women older than 60 years. One patient suffered from headache and seizures, the other one presented with behavioral disturbance. Radiological features depended on the amount of fat accumulation within the tumor. Surgical treatment allowed complete resection in both cases without any complications. Both meningiomas were of transitional-type and were apparently composed of 2 populations of cells: meningothelial cells and lipid-laden cells resembling mature adipocytes. Immunohistochemical study showed that lipid-laden cells expressed EMA, CD99, and progesteron receptor, favoring a meningothelial differentiation rather than an adipocytic lineage. CONCLUSION: Our study strongly suggests that lipomatous meningioma results from an accumulation of lipid inside meningothelial cells rather than a true metaplasia.     

Immunohistological evaluation of macrophage infiltrates in brain tumors. Correlation with peritumoral edema

Peritumoral edema is one of the most serious complications of intracranial neoplasms; however, the exact pathogenesis of this condition is still unknown. To explore the effect of macrophages in brain tumors on the pathogenesis of peritumoral edema, 42 specimens of primary or metastatic brain tumors were studied. Frozen sections were examined by an immunoperoxidase staining technique with anti-Leu-M3 monoclonal antibody. Eight of 14 gliomas demonstrated Leu-M3-positive cell (macrophage) infiltration. The two glioblastomas showed a moderate or marked degree of macrophage infiltration. Twelve of 16 meningiomas demonstrated varying degrees of macrophage infiltration. All six metastatic brain tumors exhibited prominent macrophages in intra- and peritumoral tissues. Four acoustic neurinomas and two hemangioblastomas showed a slight to moderate degree of macrophage infiltration. Excellent correlation was found between the degree of macrophage infiltration seen on immunoperoxidase staining and the peritumoral edema detected on computerized tomography brain scans of patients with supratentorial tumors, especially meningiomas. Macrophages are known to secrete various substances (including arachidonate metabolites) that may interfere with vascular permeability. These data suggest that macrophages infiltrating brain tumors may play an important role in the pathogenesis of peritumoral edema.     

The effect of 5-lipoxygenase inhibition on blood-brain barrier permeability in experimental brain tumors.

To determine if leukotrienes are important mediators of vascular permeability in brain tumors, the effect of 5-lipoxygenase inhibitors on blood-tumor barrier permeability in rats harboring HK Walker 256 brain tumors was examined using quantitative autoradiography with alpha-14C-aminoisobutyric acid. The 5-lipoxygenase enzyme converts arachidonic acid to leukotrienes. Three 5-lipoxygenase inhibitors were utilized: BW755C, nordihydroguaiaretic acid, and AA-861. All three 5-lipoxygenase inhibitors significantly decreased vascular permeability both within the tumors and in brain adjacent to tumor. This suggests that capillary permeability in and adjacent to tumors is influenced by endogenous leukotrienes and that leukotrienes play an important role in brain tumor edema.     

Preservation of hearing in patients undergoing excision of acoustic neuromas and other cerebellopontine angle tumors

Microsurgical techniques have made it possible to identify and preserve the cochlear nerve from its origin at the brain stem and along its course through the internal auditory canal in patients undergoing removal of small or medium-sized acoustic neuromas or other cerebellopontine angle (CPA) tumors. In a consecutive series of 100 patients with such tumors operated on between 1975 and 1981, an attempt was made to preserve the cochlear nerve in 23. The decision to attempt to preserve hearing was based on tumor size and the degree of associated hearing loss. In cases of unilateral acoustic neuroma, the criteria for attempted preservation of hearing were tumor size (2.5 cm or less), speech reception threshold (50 dB or less), and speech discrimination score (60% or greater). In patients with bilateral acoustic neuromas or tumors of other types, the size and hearing criteria were significantly broadened. All patients were operated on through a suboccipital approach. Hearing was preserved postoperatively in six (31.6%) of the 19 patients with unilateral acoustic neuromas, although the cochlear nerve was preserved in 16. Of the six patients with postoperative hearing, three retained excellent hearing, and the other three had only sound awareness and poor discrimination. Hearing was preserved in three cases with other CPA tumors, including an epidermoid cyst and small petrous meningiomas in the internal auditory canal. Of the two cases with bilateral tumors, hearing was preserved in one. Of the 23 patients in whom hearing preservation was attempted, nine (39.1%) had some postoperative hearing, which in six was equal to or better than the preoperative level. Thus, it is worthwhile to attempt hearing preservation in selected patients with CPA tumors.     

Intrinsic brain-stem tumors of childhood: surgical indications

This report summarizes the first author's experience with radical excision of intrinsic non-exophytic brain-stem gliomas in 34 pediatric patients. On retrospective analysis, these tumors may be classified into three subgroups: focal, diffuse, and cervicomedullary. A focal neoplasm is a circumscribed mass less than 2 cm in diameter and without associated edema. Tumors of a larger size or in which the "focal" neoplasm is associated with a large area of apparent edema are classified as diffuse. Cervicomedullary neoplasms occur at the junction of the medulla and spinal cord and involve both of the structures but do not extend rostrally into the pons. A radical tumor excision was carried out in all patients, and the only mortality and morbidity occurred in children harboring diffuse gliomas. All of the diffuse gliomas were malignant (grade III or IV astrocytomas), whereas three of the four focal astrocytomas and all of the cervicomedullary tumors were grade II astrocytomas. No patient with a diffuse astrocytoma was benefitted by surgery, while two of the focal astrocytomas and all of the cervicomedullary neoplasms either became stable or improved postoperatively. It is concluded that, although surgery may be accomplished within the substance of the brain stem with low morbidity and mortality rates, it is not indicated for malignant astrocytomas as it has no impact on the biology of the neoplasm. Therefore, while primary radical excision is recommended for cervicomedullary neoplasms, which are often benign, the more traditional radiation therapy and/or chemotherapy remain appropriate for tumors above the medulla.     

Transcranial color-coded real-time sonography in the evaluation of intracranial neoplasms and arteriovenous malformations.

Transcranial color-coded real-time sonography (TCCS) was performed in 57 patients with primary intracranial brain tumors (n = 49) or arteriovenous malformations (n = 8) to evaluate its diagnostic potential. In 46 patients (81%), lesions could be identified employing this technique. In 7 patients, transcranial ultrasound examination was not feasible because of bone thickness; in the remaining 4 patients, the tumor was indistinguishable from adjacent brain tissue despite sufficient insonation, suggesting that these neoplasms are isoechogenic. The sonographic features of brain tumors were very similar: a hyperechogenic matrix of the lesion was interspersed by hypoechogenic pixels. Larger hypoechogenic areas (0.5-1 cm) gave evidence of tumor necrosis. Differences between the findings of TCCS and computed tomography concerning tumor size were found in 7 patients, in whom TCCS revealed an area of smaller extension within the corresponding hypodense area on the computed tomographic scan. Perifocal brain edema could not be detected by ultrasound examination. In 13 patients, a thin, hypoechogenic peritumoral halo was disclosed that did not correlate with perifocal brain edema identified by computed tomography and that may have been due to compression of adjacent parenchyma. In patients with arteriovenous malformations, TCCS permitted the identification of the main feeders, the nidus, and the draining venous system by color-coded depiction of intravascular blood flow. In conclusion, TCCS is an additional method for initial diagnosis and highly suitable for follow-up in tumor patients and provides valuable information about tissue characteristics and blood flow.     

Small cell carcinoma of the breast: a clinicopathologic and immunohistochemical study of nine patients

Small cell carcinoma of the breast is an uncommon neoplasm that has been reported rarely in the literature. The aim of this study was to characterize better the pathologic and immunohistochemical features of this neoplasm. Nine examples of mammary small cell carcinoma were retrieved from the authors' consultation files and reviewed. The patients ranged in age from 43 to 70 years. Two patients had a previous history of cutaneous malignant melanoma and one had prior lobular carcinoma in situ and atypical duct hyperplasia in the same breast as the small cell carcinoma. Eight patients presented with a mass in the breast; one patient had an axillary tumor. Tumor size ranged from 1.3 to 5.0 cm (mean, 2.6 cm). Histologically, the nine tumors had characteristics of small cell carcinoma with high mitotic activity and necrosis. A dimorphic histologic appearance was observed in four tumors. In one instance, this consisted of small cell carcinoma merging with invasive lobular carcinoma. In three cases, small cell carcinoma was present together with invasive, poorly differentiated duct carcinoma; invasive carcinoma with "lobular and gland-forming elements"; and focal squamous differentiation, respectively. Lymphatic tumor emboli were identified in four instances. An in situ component was seen in seven tumors; five were of the small cell type in ducts and two were of the ductal type with high nuclear grade. Immunohistochemical analysis showed consistent staining for cytokeratin markers but variable staining with neuroendocrine markers. Sixty-six percent of the tumors (six of nine) were reactive for chromogranin, synaptophysin, or peptide hormones, including four positive for chromogranin and synaptophysin, one positive for synaptophysin and calcitonin, and one positive for calcitonin alone. One tumor that was reactive for chromogranin and synaptophysin also contained calcitonin immunoreactive cells, whereas gastrin-releasing peptide was present in two other tumors that were also positive for chromogranin. Leu 7 was positive in three cases that were reactive for either chromogranin or synaptophysin. Five tumors were estrogen and progesterone receptor-positive. All tumors were positive for bcl-2 and negative for HER2/neu. Patients were treated by mastectomy (n = 3) or lumpectomy (n = 6). Eight underwent an axillary dissection that revealed metastatic carcinoma in four patients. Seven patients received adjuvant chemotherapy and four patients received radiation. Two patients also received tamoxifen treatment. Metastases developed in two patients (22%) with a follow-up period of 11 and 32 months. All patients were alive at last follow up 3 to 35 months after treatment. When compared with published reports of mammary small cell carcinoma, our results show that the prognosis in these patients may not be as poor as previously suggested.     

Unusual presentations of cerebral solitary fibrous tumors: report of four cases

OBJECTIVE AND IMPORTANCE: Four rare cases of central nervous system solitary fibrous tumors (C-SoFTs) are described. This tumor has not previously been reported in children or in deep cortical structures. Three of these tumors occurred in the posterior fossa. Only four cases in the posterior fossa have been described previously. Nine years after its debulking from the posterior fossa, one tumor disseminated to the spine, lung, and liver. Only one such aggressive C-SoFT has been described previously. CLINICAL PRESENTATION: A 7-year-old child had had 1 year of right-sided weakness at presentation. Magnetic resonance imaging scans revealed a left basal ganglia lesion. A 49-year-old woman and a 30-year-old man presented after experiencing headaches for months. Magnetic resonance imaging scans in these patients revealed a tumor in the fourth ventricle and right jugular foramen, respectively. A 55-year-old man had spinal, liver, and lung dissemination of a previous posterior fossa tumor at presentation. INTERVENTION AND TECHNIQUE: All four patients underwent craniotomy for resection or subtotal removal of the tumor. Intraoperative observations noted solid well-encapsulated tumors. Immunohistochemistry confirmed C-SoFTs in all four cases. CONCLUSION: C-SoFTs are rare central nervous system, typically dural-based, tumors. They frequently are overlooked in the differential diagnosis of solid central nervous system tumors. Our findings suggest that these tumors can occur at any age and in most locations, regardless of proximity to the meninges (basal ganglia and ventricle), suggesting that the cells of origin are not meningothelial, but rather the mesenchyme of the cerebral vasculature. T1- and T2-weighted magnetic resonance imaging was notable for areas of hypointensity and of hyperintensity best described as patchy or a ying-yang appearance in all cases. Delayed extracranial metastasis may be noted.     

Expression of matrix metalloproteinases 2 and 9 in meningiomas associated with different degrees of brain invasiveness and edema.

OBJECT: Meningiomas display clinical characteristics that vary from very benign to clearly malignant with rapid invasive growth and metastasis. Benign meningiomas differ in their invasiveness and concomitant edema. This study was undertaken to analyze the expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively) in meningiomas associated with different degrees of brain invasion and edema. METHODS: Tissue samples from 16 meningiomas were selected according to tumor invasiveness from a consecutive series of patients. Samples were analyzed for expression of both MMP-2 and MMP-9 by using in situ hybridization. The meningiomas consisted of three types: Group I, benign meningiomas that did not interfere with the arachnoid plane and exhibited no edema; Group II, benign meningiomas that invaded the arachnoid plane and caused edema; and Group III, aggressive and malignant meningiomas that caused edema and displayed brain invasion. In all 16 tumors analyzed, MMP-2 mRNA was identified. Levels of expression of MMP-2 mRNA were similar in all samples, and no correlation with increasing tumor invasiveness or associated edema could be detected. Expression of MMP-9 mRNA was identified in 14 of the 16 tumors, and a clear correlation with increasing tumor invasion into the brain was noted. CONCLUSIONS: Meningiomas express both MMP-2 and MMP-9. Tumor invasiveness, which ranged from minor with respect to the arachnoid membrane and progressed to frank brain invasion, correlated with the extent of MMP-9 expression. The findings indicate that MMP-9 expression and brain invasion are relevant mechanisms that must be interfered with in the treatment of aggressive and malignant meningiomas. No such correlation with MMP-2 was found.     

Long-term survival of patients treated with BCNU for brain tumors.

The authors present three patients who, after excision and irradiation of their brain tumors, were treated with BCNU for recurrence. All three patients responded well and now are without evidence of tumor, 37, 30, and 36 months after BCNU was stopped. Although these patients represent only a small fraction of those treated with BCNU, they indicate the potential role of chemotherapy in the management of glial tumors.     

Avoidance of vascular compression in decompressive surgery for brain edema caused by trauma and tumor ablation.

BACKGROUND: In case of severe brain swelling especially caused by trauma or other operative manipulation (tumor ablation), decompressive craniectomy with durotomy has not resulted in significant chances of recovery. Decompressive craniectomy has been defined only as an option within guidelines. METHOD: A new operative technique was developed to improve the efficacy of decompressive surgery. With an increase in intracranial pressure (ICP) threatening with brainstem herniation, wide bilateral craniectomy was carried out, followed by dura opening and subsequent formation of a vascular tunnel in a simple way--using hemostatic sponge cushions--around the main cortical veins at the entering points of the herniated area. The maintenance of vessel patency prevents the herniated brain segment from venous congestion, i.e., from further swelling and necrosis. RESULTS: Twenty operations with traumatic brain edema were performed using this vascular tunnel method. All patients were exposed to surgery in the state of coma. One operation was performed after tumor removal. The results were promising in comparison with the well-known surgical or conservative treatment. DISCUSSION: Applying very strict selection criteria (Glasgow coma scale < 6, signs of severe edema on CT, or intracranial pressure permanently > or = 30 mmHg) in this small series of patients with severe brain injury, good results were achieved using the new operative technique. In case of postoperative edema after tumor ablation, it also showed promising results.     

The role of radiosurgery in the management of chordoma and chondrosarcoma of the cranial base

Despite conventional multimodality treatment (surgery and fractionated radiation therapy), recurrence and clinical progression of cranial base chordomas and chondrosarcomas are common. The malignant behavior of these tumors is a result of their critical location, locally aggressive nature, and high recurrence rate. To explore the role of radiosurgery in the treatment of these skull base neoplasms, we assessed its use in four patients with chordoma and two with chondrosarcoma. In five of the patients, radiosurgery was used as adjuvant therapy for residual or recurrent tumors after surgical debulking, and in one patient with a chordoma, it was the primary treatment. No patient received fractionated external beam radiotherapy. All tumors were less than 30 mm in diameter and were treated with 20 Gy to the tumor margin. Skull base computed tomography and magnetic resonance images were essential to define the anatomic relationships between tumor and adjacent basal structures. During follow-up (mean, 22 mo; range, 8-36 mo), we found no progression of the treated tumor volume in any patient. Neurological deficits before treatment improved in three patients; the other three patients remained in stable neurological condition. Serial follow-up imaging studies demonstrated that two patients showed reduction in tumor size and four patients had no tumor growth. In one patient, a metastatic parietal lobe chondrosarcoma developed and was treated by microsurgery. Another patient showed tumor progression outside of the radiosurgical treatment volume. Our results attest to the value of stereotactic radiosurgery as an adjuvant or primary treatment for selected patients with chordoma or chondrosarcoma and demonstrate its potential advantages over standard fractionated irradiation. Analysis of the long-term clinical and imaging effects after radiosurgery is warranted.     

A case of metastatic suprasellar tumor with edema along the optic pathway

A rare case in presented of a patient with edema formation along the optic pathway, which was caused by metastatic suprasellar tumor mimicking craniopharyngioma. A 63-year-old female with visual disturbance, diabetes insipidus, and symptomatic panhypopituitarism was admitted to our hospital. CT images showed a suprasellar mass lesion. MR images demonstrated a heterogeneously enhanced tumor and edema along the optic nerve and tract. Although no cystic component is shown in radiological findings, these features are commonly observed in cases of craniopharyngioma. The patient underwent removal of the tumor by the transcranial approach. Since histological examination revealed adenocarcinoma, the tumor was diagnosed as metastatic brain tumor originating from non-recurrent rectal cancer operated on eight years previously. Conventional radiotherapy with a dose of 50GY was performed for the residual tumor. The tumor size was unchanged, but the edema had disappeared 7 months after the operation. Edema spreading along the optic tract was reported as a characteristic MR finding for diagnosis of craniopharyngiomas as distinguished from other common parasellar tumors. However, it is suggested that edema of the optic pathway seems to be caused not only by craniopharyngioma but also other suprasellar lesions. Even if there was a characteristic radiological finding for some specific diseases, metastasis should be kept in mind as a differential diagnosis, because of its various appearance in neuroimages.