Michele Caniglia

Angiogenesis in intracranial meningiomas: immunohistochemical and molecular study

Much of the morbidity of intracranial meningiomas is related to the degree of tumour vascularity and the extent of peritumoural vasogenic oedema. Several studies have shown that vascular endothelial growth factor (VEGF) is up‐regulated in meningiomas, although its relationship with tumour vasculature is still unclear. In order to better understand the angiogenic assessment of intracranial meningiomas, we analysed its vascular pattern, both as number and as morphologic configuration of microvessels. Moreover, we investigated the mRNA‐VEGF expression, relating this expression to vascular pattern. A total of 40 intracranial meningiomas, classified as benign (31 cases), atypical (7 cases), and anaplastic (2 cases) were analysed. RT‐PCR analyses of mRNA‐VEGF and competitive‐PCR were performed. VEGF expression and microvessel density (MVD) were also immunohistochemically investigated. Grade II–III meningiomas showed numerous small microvessels (mean: 34), while the majority of Grade I showed few larger vessels (mean: 13.09) (P = 0.000003). A microvessel pattern overlapping into atypical subtype was found in eignt of the 31 (25.8%) Grade I meningiomas. A significant association was found between grading and vascular pattern (P = 0.0002), as well as between the MVD and the immunohistochemical expression of VEGF (P = 0.0005). The expression of mRNA agreed with the immunohistochemical expression of the protein (P < 0.0001). A total of 39 cases expressed the 121 VEGF isoform and, among these, 28 cases also expressed the 165 isoform. Only 9 cases expressed both isoforms 165 and 189. Grade II and III meningiomas showed a preponderant expression of soluble isoforms (121 and 165). These results prompt us to speculate that the microvessel pattern could underlie a higher metabolic demand, probably due to a rapid growth with a consequent worse clinical behaviour of the tumour. In this sense, the vascular pattern may be used as a prognostic factor, in order to mostly focus attention on those Grade I meningiomas which have a higher likelihood of either recurrence or development of perilesional oedema. The pattern of vasculature itself seems to be dependent on the types of VEGF isoforms: the Grade II–III meningiomas (that presented numerous microvessels) expressed the soluble isoforms 121 and 165, while the isoform 189 was more frequently detected in Grade I meningiomas.

Transnasal endoscopic surgery for selected orbital cavernous hemangiomas: our preliminary experience.

Endoscopic transnasal approaches to the orbit have been recently described and they have been proposed as an option in the surgical management of medial and inferior orbital lesions.

Malignant transformation of intramedullary melanocytoma: case report.

OBJECTIVEMeningeal melanocytomas are low-grade primary melanocytic tumors with benign histological features and a favorable clinical prognosis. Transition from meningeal melanocytoma to primary melanoma of the central nervous system is exceptionally rare, with only 5 cases having been previously reported. Here, we discuss a case of malignant transformation of an intramedullary melanocytoma to primary melanoma and review the pertinent literature. CLINICAL PRESENTATIONA 79-year-old woman presented with progressive paresis in the lower limbs followed by sphincter dysfunction. Magnetic resonance imaging scans disclosed an intramedullary lesion located at the T10–T11 level. INTERVENTIONThe patient underwent subtotal resection of an intermediate-grade melanocytoma. Two years later, the tumor recurred locally, and the patient underwent additional surgery to remove the intramedullary mass. The histological findings of the tumor were consistent with an intramedullary malignant melanoma. CONCLUSIONThe malignant transformation of melanocytic tumors of the central nervous system may occur years after surgical treatment, and its incidence remains unknown. Emphasis should be placed on the importance of careful and continued follow-up monitoring of the tumor.

The role of somatostatin in vasogenic meningioma associated brain edema.

Many tumors, including meningiomas, express somatostatin receptors, suggesting the application of somatostatin analogues for therapy and diagnosis. Sixty percent of meningiomas are associated with perilesional edema, whose development seems to be related to the vascular endothelial growth factor, although it requires an efficient pial blood supply. However, in several neoplastic models, other mediators seem to cooperate with vascular endothelial growth factor in regulating angiogenesis. We evaluated somatostatin receptors (sst2) in relation to the possibility that somatostatin analogues may influence vascular endothelial growth factor production with reduction of edema. Of 35 studied meningiomas, 21 presented peritumoural edema. Vascular endothelial growth factor, microvascular density and pial blood supply were significantly related to the edema (P = 0.0001, P = 0.0001, P = 0.0005). Similarly, a relation was found between sst2 and microvascular density (r = 0.58, P <0.001) and between sst2 and vascular endothelial growth factor expression (P = 0.03). This suggests that somatostatin analogues may be relevant for the treatment of meningiomas.

Redistribution of cerebropetal blood flow in patients with carotid artery stenosis measured non-invasively with fast cine phase contrast MR angiography

The purpose was to evaluate the blood flow redistribution in the neck vessels of patients with internal carotid artery (ICA) stenosis. Eighty-six patients with ICA stenosis underwent contrast-enhanced magnetic resonance angiography (CEMRA) and fast 2D phase contrast (2D-PC) sequence to measure the mean blood flow (MBF) of ICA, basilar artery (BA) and middle cerebral artery (MCA). CEMRA revealed 53 severe stenoses, 45 moderate stenoses and 3 occluded vessels. Patients with a unilateral severe ICA stenosis had a significantly reduced MBF of the ICA compared to the control group; the MBF reduction of the severely stenosed ICA was less conspicuous if associated with a controlateral severe stenosis. The MBF of the BA increased significantly in the presence of the bilateral severe ICA stenosis and in the ICA occlusion. The MBF of the MCA was unchanged in the presence of various degrees of ICA stenosis. Measurement of MBF with fast PC MRA permits cerebropethal blood flow assessment and gives additional information in grading ICA stenosis. The reduced MBF of a severe ICA stenosis has to be considered with caution since it depends also on the status of the controlateral ICA and may be considered a confident parameter only in case of unilateral carotid stenosis.

Immunohistochemical and molecular study of radiation-induced multiple meningiomas with pleural and pulmonary metastasis

In the present study, the telomerase activity and the putative alterations of genes involved in cell-cycle control (p53, Fas and pRb) were investigated in a radiation-induced meningioma with multiple recurrences and pleural-pulmonary metastases (the patient, a 34-year-old male, had a history of carcinoma of the tongue of testicular lymphocytic lymphoma). Expression of VEGF and vasculature pattern were also studied. Expression of VEGF, pRb and p53 were evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded samples of the tumor. VEGFmRNA was determined by competitive PCR. Fas, FasL and hTERT were evaluated by RT-PCR. Telomerase activity was examined by the TRAP assay. An intense vascularization was observed, supported by high expression of VEGFmRNA (isoforms 121 and 165). pRb and p53 were overexpressed. Fas was undectable with PCR, whereas FasL was positive. Furthermore, the lesion showed an elevated telomerase activity (TPG, 22), according to the high expression of hTERT. These findings emphasized that even among generally benign neoplasms, such as meningiomas, some highly malignant tumors may develop, as in our case, in which several mechanisms were activated in the cancer progression to guarantee the immortalization of cellular clones (angiogenic phenomenon, activation of telomerase and of anti-apoptotic mechanisms) and the blood spread. Thus, the data illustrate the importance of searching for genetic aberrations (which are a hallmark of malignancy) in meningiomas, as predictive and reliable factors of the possibility to recur and to metastasize.

Wrapping of intracranial aneurysms: Single-center series and systematic review of the literature

Background. Circumferential wrapping of the aneurysm wall with a variety of materials is a well-known therapeutic approach for the repair of unclippable intracranial aneurysms (IAs). Wrapping materials can stimulate foreign-body inflammatory reactions and parent artery narrowing with resultant ischemic stroke. In this study, a single-center retrospective review of the outcome with wrapping of IAs is presented beside an analysis of existing literature. Methods. For the institutional analysis, all patients who underwent wrapping of IAs in the last five years were analyzed. For the analysis of the literature, a MEDLINE search between 1990 and the present was performed for clinical series reporting wrapping of IAs. Specifically, the risk of rebleeding, cerebrovascular complications, and the incidence of granuloma formation were evaluated. Results. Two hundred and ninety patients with IA were surgically treated in our department. Fifteen patients (5.2%) underwent wrapping of IA. Early parent artery narrowing occurred in one patient (6.7%) and was associated with ischemic stroke. Delayed cerebrovascular complications, including parent artery narrowing (one case), granuloma formation (one case), and fatal bleeding from an unruptured aneurysm, occurred in three patients (20%). For the review of the literature, 197 cases of wrapped aneurysms were collected. Bleeding after wrapping occurred in 16 (12%) of the patients with ruptured aneurysms. Acute ischemic complications were reported in 7 cases (3.5%) and granuloma formation was observed in 3 patients (1.5%). Conclusions. These data suggest that the microsurgical wrapping of IAs present a risk of ischemic complications and granuloma formation. Additionally, the rebleeding rate of ruptured aneurysms remains high, although still lower than the natural history of untreated ruptured aneurysms

Cerebellar Mass as a Location of Acute Lymphoblastic Leukaemia

A 22-year-old man with acute lymphoblastic leukaemia was referred to our observation for headache, cervical pain and sopor. A computed tomography study revealed triventricular obstructive hydrocephalus due to a left cerebellar hyperdense mass impinging on the fourth ventricle. A magnetic resonance study demonstrated an area of hyperintensity on T2-weighted images, hypointensity on T1, restricted diffusivity and contrast enhancement involving the left hemispherical cerebellar cortex and the vermis and causing cerebellar herniation. After surgical excision of the lesion, histological examination revealed an infiltrate of lymphoblastic leukaemia with B cells. Leukaemic intracranial masses are rare. Our report describes a case presenting a cerebellar mass of leukaemic tissue characterized by high cellularity and low apparent diffusion coefficient value comparable to acute ischaemia. Therefore leukaemic intracranial mass has to be considered in the differential diagnosis of cerebellar masses.