Balloon cells in human cortical dysplasia and tuberous sclerosis: isolation of a pathological progenitor-like cell.

Neural stem cells are present in the human post-natal brain and are important in the development of brain tumours. However, their contribution to non-neoplastic human disease is less clear. We have tested the hypothesis that malformations of cortical development contain abnormal (pathological) stem cells. Such malformations are a major cause of epilepsy. Two of the most common malformations [focal cortical dysplasia (FCD) and cortical tubers] are characterised by the presence of a population of abnormal cells known as balloon cells. The identity of these cells is unknown but one hypothesis is that they are an abnormal stem cell that contributes to the pathogenesis of the malformation. We have characterised in tissue, and isolated in culture, an undifferentiated population of balloon cells from surgical resections of FCD and cortical tubers. We show that beta1-integrin labels a sub-population of balloon cells with a stem cell phenotype and show for the first time that these cells can be isolated in vitro. We have characterised the immunohistochemical, morphological and ultrastructural features of these cells. This is the first isolation of an abnormal cell with features of a progenitor/stem cell from a non-neoplastic disease of the brain.

Primary intra-diploic meningioma in a child.

BACKGROUND: Primary intra-diploic meningiomas are uncommon in childhood and, at the clinical onset, may be confused with other and more frequent bone tumours because they lack specific clinical and radiological characteristics. Surgery is indicated not only to remove the lesion but also to obtain an accurate histological diagnosis. CASE REPORT: We report the case of a young girl who presented with a recently developed subcutaneous hard mass in the left pterional region. Neuroradiological investigations revealed an intra-osseous lytic mass with a sclerotic reaction. Diagnosis was possible only after the total removal of the tumour and its histological examination.

Aesthetic compatibility assessment of consolidants for wall paintings by means of multivariate analysis of colorimetric data.

BACKGROUND AND METHODS: Wall paintings and architectural surfaces in outdoor environments are exposed to several physical, chemical and biological agents, hence they are often treated with different products to prevent or slow down their deterioration. Among the factors that have to be taken into account in the selection of the most suitable treatment for decorated surfaces, the aesthetic compatibility with the substrate is of great importance in the cultural heritage field; minimizing colour variation after treatment application is a crucial issue in particular for painted surfaces. In the framework of the European Project Nanomatch the color variation induced on wall painting mock-ups by the two innovative consolidants (calcium alkoxides) developed was evaluated using colorimetry in comparison with two traditional products. In this work these innovative consolidants have been also tested in combination with two commercial biocides and the results of colorimetric measurements discussed. Moreover, as the univariate approach didn't allow to draw clear conclusions on the relation between the different sources of data variability, multivariate analysis was performed on colorimetric data. RESULTS: Principal Component Analysis and multi-way Parallel Factor Analysis (PARAFAC) were successfully applied to colorimetric data to investigate the short-term effects of the application of different consolidants on wall painting surfaces, making it possible to study at the same time the different sources of data variability, i.e. treatments, painting techniques, pigments. Finally, a ranking list of the treatments under study in terms of colour variation induced on the surface was established, in function of the painting technique and pigment, taking also in consideration the combination consolidant/biocide. In particular, given the true multi-way nature of the data, PARAFAC model turned out to be extremely useful in the study of the dependence of colour variation on pigments, a critical issue for painted surfaces, that was not clear using univariate approach. CONCLUSIONS: Multivariate approach to colorimetric data and especially 3-way PARAFAC method resulted a powerful technique to evaluate in short-term the color compatibility of consolidants for wall paintings, improving data interpretation and visualization, and thus outperforming the univariate statistical analysis.

Human brain tumors: multidrug-resistance P-glycoprotein expression in tumor cells and intratumoral capillary endothelial cells.

Malignant brain tumor is a lethal disease with currently available treatment options having a limited impact on outcome. Nevertheless, novel therapeutic approaches combined with genetic prediction of chemosensitivity have, in the last decade, significantly improved clinical benefit for the treated patients. The fine characterization of the MDR1 gene encoding for P-glycoprotein (MDR1-Pgp) in brain tumors may be a crucial determinant for evaluating the long-term efficiency of specific anti-cancer compounds. By using a very high specific monoclonal antibody, the MDR1-Pgp was immunodetected in 34 out of 43 grade IV, 6 out of 10 grade III, 4 out of 7 grade II, and 1 out 3 grade I brain tumors. MDR1-Pgp resulted hyper-expressed, both in vessels and in neoplastic cells from the majority of tumors examined, compared to normal parenchyma. This study demonstrates that the MDR1 gene can be detected in all grade tumor brain malignancies and in endothelial cells of newly formed capillaries, thus, impairing drug access at the tumor cell level. Although the role of MDR1-Pgp in tumor blood vessels needs to be further examined and more clearly defined, drug resistance in malignant brain tumors may result from characteristics not only of tumor vasculature but also of neoplastic cells.

Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase.

BACKGROUND: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro- and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). METHODS: The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. RESULTS: The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (<31%) or recommended (>31%). CONCLUSIONS: The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.

Intramedullary capillary hemangioma associated with hydrocephalus in an infant.

This 3-month-old child presented with an enlarging head circumference arising from communicating hydrocephalus with large subarachnoid spaces in the posterior fossa. Neuroimaging performed to clarify the origin and pathogenesis of the hydrocephalus revealed a vascular lesion within the dorsal spinal cord. Insertion of a cerebrospinal fluid shunt and total removal of the spinal tumor were performed successfully. Histological examination of the medullar lesion demonstrated a capillary hemangioma. Proposed mechanisms for increased intracranial pressure and spinal cord lesions are presented. A spinal hemangioma in this age range associated with hydrocephalus has not been reported previously, but spinal lesions must be considered in the presence of hydrocephalus with no clear origin.

Progressive hemispheric shrinking in hemimegalencephaly: a possible role for seizure-related neuronal loss.

Hemimegalencephaly (HME) is a developmental brain lesion consisting of a unilateral enlarged, dysplastic, and often highly epileptogenic cerebral hemisphere. Most patients exhibit early onset intractable seizures, status epilepticus, hemiplegia, hemianopsia, and developmental delay. Major surgical procedures are advocated for limiting the devastating consequences of epilepsy. We studied a female with HME, early onset intractable seizures and recurrent status epilepticus, in whom progressive hemiatrophy of the enlarged hemisphere and normal growth of the contralateral hemisphere, exceeding the size of the dysplastic hemisphere, was demonstrated by magnetic resonance imaging. Histopathology, following functional hemispherectomy at the age of 7 years, demonstrated severe neuronal loss with an elevated number of cells exhibiting the morphological and biochemical features of apoptosis. Eighteen months after surgery the patient was seizure-free (Engel class I) and exhibited improved motor and language skills, alertness and social behaviour. We hypothesize that nearly continuous seizure activity might sustain seizure-induced brain injury in the dysplastic hemisphere but causal heterogeneity and associated anatomical factors may influence differently the individual predisposition to atrophic changes.