Antonia Cimmino

miR-155 is up-regulated in primary and secondary glioblastoma and promotes tumour growth by inhibiting GABA receptors.

An altered expression of microRNAs (miRNAs) contributes both to the development of cancer and to the progression of the disease. Malignant tumours and tumour cell lines have widespread deregulated expressions of miRNAs compared to normal tissues. In this study, we investigated the expression profiles of 340 mammalian miRNAs in 93 cases of multiform glioblastoma (primary and secondary glioblastoma tumours), by means of DNA microarrays. We show that the expression profiles of 10 miRNAs can distinguish primary from secondary glioblastoma types. Moreover, we found elevated miR-155 levels in primary and secondary glioblastoma tissues as well as in glioblastoma primary cultures. We hypothesised that γ-aminobutyric acid A receptor 1 (GABRA1) is a miR-155 target, and studied the correlation between miR-155 up-regulation and the GABRA1 protein in cultured glioblastoma cells by miRNA silencing. We show that a decrease in miR-155 expression to normal levels restores the expression of GABRA1, making glioblastoma cells sensitive to signals that inhibit cell proliferation mediated by GABRA1. In conclusion, the expression patterns of different miRNAs characterise primary and secondary glioblastomas. The aberrant overexpression of miR-155 contributes to the malignant phenotype of glioblastoma cells removing growth inhibition.

Radiation-induced intracranial meningiomas: review of six operated cases

It is well known that radiation can induce meningiomas. These tumors usually arise in patients with a history of low-dose radiation to the scalp for treatment of tinea capitis or high-dose radiation for a previous brain tumor. Radiation-associated meningiomas (RAMs) morphologically resemble their spontaneously arising counterparts. However, RAMs frequently present a more malignant phenotype and, as such, are diagnosed as “atypical” or “aggressive” meningiomas and occur predominantly in younger patients. This paper describes six cases of radiation-associated intracranial meningiomas in patients previously treated with low-dose radiation to the scalp for tinea capitis.

Pre-operative subarachnoid haemorrhage in a patient with spinal tumour

Despite the guidelines for the treatment of aneurysms or spinal tumours having been described, the coexistence of both pathologies makes their management difficult. In fact, when subarachnoid haemorrhage (SAH) occurs, a correct surgical assessment of the spinal tumour and planning of suitable anaesthesiology are necessary to reduce the risk of cerebral vasospasm (CVS) and subsequent ischaemic complications (1, 2). This holds true not only in the neurosurgical field but in any other emergency surgical practice, requiring general anaesthesia, after early SAH. This paper reports the case of a patient diagnosed with cauda equina syndrome caused by lumbar schwannoma who presented with sudden cephalalgia.

Primary intramedullary primitive neuroectodermal tumor (PNET) – case report and review of the literature

Spinal primitive neuroectodermal tumors (PNET) are very rare tumors, and intramedullary localization is even less common. Indeed, amongst the 23 cases of the spinal PNET described in the literature, only eight cases had an intramedullary localization. Following the WHO 2000 classification, PNETs have been considered embryonal tumors composed of undifferentiated neuroepithelial cells with a capacity of differentiation into different cellular lines, such as astrocytic, ependymal, melanotic and muscular. They have been considered to arise from a neoplastic transformation of primitive neuroepithelial cells, thereby making their presence possible in any part of the central nervous system. The optimal treatment for these malignant tumors is not yet clear, although, over the years, radiotherapy has been considered the best treatment for spinal PNETs. The described case is that of a 38‐year‐old man with a primary intra‐extramedullary PNET, treated by laminectomy, open biopsy and chemotherapy. The patient, 18 months after the onset of his symptomatology, died without cerebral tumor involvement.

Central neurocytoma: two case reports and review of the literature

Central neurocytomas are low grade tumours usually located in the lateral ventricles next to Monro foramina. This paper reviews the literature on central neurocytomas observed in the last few years and discusses their clinical, histopathological, immunohistochemical and genetic characteristics. Important correlations between therapeutic strategies and biological findings as well as new genetic discoveries are also discussed. Two illustrative cases in which the authors report preliminary results about molecular analysis of some genetic markers are described.

Intramedullary solitary fibrous tumor of dorsal spinal cord.

Solitary fibrous tumors (SFT) are rare neoplasms of mesenchymal origin involving soft tissues, mainly serosal sites; the spinal cord location is uncommon. We report a case of SFT occurring in the thoracic spinal cord, discussing histological, ultrastructural and molecular aspects. A 75‐year‐old woman with an MRI suggesting a dorsal intracanalar lesion was admitted to our institution. T5–T7 laminectomies were performed and an intramedullary tumor was discovered. The tumor arose within the spinal cord and was completely removed. Tumor samples were processed for histological, ultrastructural and molecular analysis (comparative genomic hybridization [CGH], methylation status of O6‐methylguanine–DNA methyltransferase [MGMT], p16, deleted in colorectal cancer [DCC] and death‐associated protein kinase 1 [DAPK1]). The histological examination demonstrated a proliferation of spindle‐shaped cells with a collagen‐matrix background. Immunohistochemical staining was positive for vimentin and CD34 and negative for S‐100 and epithelial membrane antigen. A histological diagnosis of SFT was made. The ultrastructural examination showed undifferentiated cells within a collagenous matrix and sparse extravascular basement membrane. CGH analysis revealed deletion of 9p21 and losses on 2q, 3p, 16q and 19q and gains on 7q; furthermore, no aberrant methylation pattern was found in the promoter region of MGMT, p16, DCC and DAPK1 genes. On the second‐year follow‐up, the patient was neurologically intact. The occurrence of SFT within the spinal cord parenchyma and its histological characteristics demonstrate that SFTs are not restricted to serosal surfaces. The course of spinal cord SFT is unknown and long‐term follow‐up is necessary. The histological, ultrastructural and molecular findings are important for the diagnosis and the authors provide a literature review of these aspects.

Cystic dilation of the ventriculus terminalis in adults

The ventriculus terminalis (VT) is a small ependyma-lined cavity within the conus medullaris that is in direct continuity with the central canal of the anterior portion of the spinal cord. Normally, such a cavity is identifiable only histologically in children and adults and can be visualized using common neuroradiological techniques only after dilation. Currently, the mechanisms of isolated dilation are not documented. The present work describes 2 cases of VT in elderly patients. Data from a histological and ultrastructural study of a case of VT dilation are reported, and the results are compared with those obtained from the VT of 5 fetuses to explain the nosological aspects of nontumoral VT lesions. Our data suggest that the site, age, and histological characteristics of the lesion allow us to define VT dilation as a nosological entity distinct from other cystic dilations of the conus medullaris.

Schnitzler’s Syndrome: Monoclonal Gammopathy Associated with Chronic Urticaria

Schnitzler’s syndrome (SS) is defined by monoclonal gammopathy and chronic urticaria combined with at least two of the following features: fever, arthralgia or arthritis, bone pain, hepato- and/or splenomegaly, palpable lymph nodes, elevated ESR, and leukocytosis. We report a 49-year-old man with monoclonal IgM gammopathy and a 4-year history of recurrent urticarial rash, unexplained fever and arthralgias. The skin biopsy from an acute lesion revealed perivascular lymphocytic infiltrates consisting of CD4+ and CD8+ T lymphocytes. To our knowledge, this is the first report of an immunophenotypic characterization of skin infiltrates in SS. A lower CD4+/CD8+ ratio of circulating T lymphocytes was also detected. SS usually has a benign course, but in 15% of patients a lymphoproliferative disorder develops.

Gliomatosis cerebri type II: two case reports

IntroductionTwo types of gliomatosis cerebri exist: Type I and Type II. We report the results of a histological and genetic study of two cases of gliomatosis cerebri Type II, correlating these results with therapy and prognosis.Case presentationTwo patients, a 52-year-old man (Patient 1) and a 76-year-old man (Patient 2) with gliomatosis cerebri II were admitted to our institution; they underwent surgical treatment and received radiotherapy and chemotherapy. At the 24-month follow-up, Patient 1 was still alive, while Patient 2 had died. The poor prognosis of Patient 2 was underlined by molecular analysis which showed that the angiogenesis related genes VCAM1 and VEGF were overexpressed, reflecting the high degree of neovascularization.ConclusionGenes involved in drug resistance and metallothioneins were highly expressed in Patient 2 and this, associated with unmethylated O6-methylguanine methyltransferase, can explain the lack of response to chemotherapy.

Giant cell angiitis of the central nervous system with atypical presentation

Giant cell angiitis of the CNS is an uncommon form of vasculitis. Neurological manifestations, both of the peripheral and CNS, are common. The most frequent manifestations are visual loss and stroke. Hemorrhagic onset is uncommon. Most cases have a fatal outcome and a tissue diagnosis is rarely established in life. We describe an unusual case of giant cell angiitis beginning as a hemorrhagic tumoral‐like lesion. The results of the histological and ultrastructural analysis have also been reported. Our case illustrates that giant cell angiitis should be considered as a cause of intracerebral hemorrhage, particularly when associated with a relapsing and remitting disease of the CNS.