Juan José Acebes

Imaging of giant pituitary adenomas

Abstract We present five proven giant pituitary adenomas studied by CT and MRI, and review the clinical and imaging findings. Our aim was to examine the radiologic appearances and to search for criteria useful in distinguishing these tumors from other sellar and suprasellar tumours, mainly craniopharyngioma. The main differences from small adenomas were high prevalence of macrocysts, a more invasive behaviour and a clinical picture dominated by mass effect rather than endocrine disturbance. Factors supporting the diagnosis of pituitary adenoma in a giant intra- and suprasellar mass include: infrasellar extension, absence of calcification and presence of low-signal cysts on T1-weighted images.

Expression of Endoplasmic Reticulum Stress Proteins Is a Candidate Marker of Brain Metastasis in both ErbB-2+ and ErbB-2− Primary Breast Tumors

The increasing incidence of breast cancer brain metastasis in patients with otherwise well-controlled systemic cancer is a key challenge in cancer research. It is necessary to understand the properties of brain-tropic tumor cells to identify patients at risk for brain metastasis. Here we attempt to identify functional phenotypes that might enhance brain metastasis. To obtain an accurate classification of brain metastasis proteins, we mapped organ-specific brain metastasis gene expression signatures onto an experimental protein-protein interaction network based on brain metastatic cells. Thirty-seven proteins were differentially expressed between brain metastases and non-brain metastases. Analysis of metastatic tissues, the use of bioinformatic approaches, and the characterization of protein expression in tumors with or without metastasis identified candidate markers. A multivariate analysis based on stepwise logistic regression revealed GRP94, FN14, and inhibin as the best combination to discriminate between brain and non-brain metastases (ROC AUC = 0.85, 95% CI = 0.73 to 0.96 for the combination of the three proteins). These markers substantially improve the discrimination of brain metastasis compared with ErbB-2 alone (AUC = 0.76, 95% CI = 0.60 to 0.93). Furthermore, GRP94 was a better negative marker (LR = 0.16) than ErbB-2 (LR = 0.42). We conclude that, in breast carcinomas, certain proteins associated with the endoplasmic reticulum stress phenotype are candidate markers of brain metastasis.

Cavernous sinus syndrome: a series of 126 patients.

The etiology of cavernous sinus syndrome (CSS) remains difficult to determine in spite of the development of neuroimaging techniques. We conducted the current study to identify clinical and imaging features that allow a reliable approach to the etiologic diagnosis of patients with CSS. We studied a consecutive series of 126 patients with CSS, defined as involvement of 2 or more of the third, fourth, fifth (V1, V2), or sixth cranial nerves, or involvement of only 1 of them in combination with a neuroimaging-confirmed lesion in the cavernous sinus. Tumors were the most common cause of CSS (80 patients). All patients with optic nerve involvement had a tumor. No patient with a normal MRI had a tumor. The lack of pain during the course of the disease (odds ratio [OR], 0.58; 95% confidence intervals [CI], 0.06-0.40), V2 involvement (OR, 12.17; 95% CI, 2.98-49.71), and male sex (OR, 3.2; 95% CI, 1.31-8.14) were independently associated with the presence of a tumor. Pain at the onset of disease (OR, 12.09; 95% CI, 3.14-46.50) and third cranial nerve involvement (OR, 4.9; 95% CI, 1.01-24.60) were independently associated with Tolosa-Hunt syndrome. Abbreviations: CI = confidence intervals, CSS = cavernous sinus syndrome, CT = computed tomography, OR = odds ratio, MRI = magnetic resonance imaging, THS = Tolosa-Hunt syndrome.

Intraventricular mass lesions of the brain.

Intraventricular tumours represent a diverse group of lesions, some of them infrequent, with a wide variety of radiological features. Determination of their precise aetiology or origin can be difficult. Nevertheless, considering patient’s age, location within the ventricles, and some specific radiological features, the radiologist should be able to narrow down the differential diagnosis. This paper reviews the characteristic radiological appearances of the diverse intraventricular lesions emphasising its differential diagnosis.

Meningeal involvement in Behçet's disease: MRI

Abstract Behçets disease is a multisystem disease that involves the central nervous system up to half of cases. Presentation with neurologic symptoms occurs in 5 % of cases and cerebral venous thrombosis is one of its major manifestations. A feature not previously reported is progressive meningeal thickening with involvement of both optic nerves. We report a patient with cerebral venous thrombosis, meningeal thickening and contrast enhancement on MRI. This patient had two other unusual features: positive antineutrophil cytoplasmic antibodies and later development of central diabetes insipidus.

Automated brain tumor biopsy prediction using single-labeling cDNA microarrays-based gene expression profiling.

Aims Gene signatures obtained from microarray experiments may be of use to improve the prediction of brain tumor diagnosis. Nevertheless, automated and objective prediction with accuracy comparable to or better than the gold standard should be convincingly demonstrated for possible clinician uptake of the new methodology. Herewith, we demonstrate that primary brain tumor types can be discriminated using microarray data in an automated and objective way. Methods Postsurgical biopsies from 35 patients [17 glioblastoma multiforme (Gbm) and 18 meningothelial meningioma (Mm)] were stored in liquid nitrogen, total RNA was extracted, and cDNA was labeled with Cy3 fluorochrome and hybridized onto a cDNA-based microarray containing 11,500 cDNA clones representing 9300 loci. Scanned data were preprocessed, normalized, and used for predictor development. The predictive functions were fitted to a subset of samples and their performance evaluated with an independent subset. Expression results were validated by means of real time-polymerase chain reaction. Results Some gene expression-based predictors achieved 100% accuracy both in training resampling validation and independent testing. One of them, composed of GFAP, PTPRZ1, GPM6B and PRELP, produced a 100% prediction accuracy for both training and independent test datasets. Furthermore, the gene signatures obtained, increased cell detoxification, motility and intracellular transport in Gbm, and increased cell adhesion and cytochrome-family genes in Mm, agree well with the expected biologic and pathologic characteristics of the studied tumors. Conclusions The ability of gene signatures to automate prediction of brain tumors through a fully objective approach has been demonstrated. A comparison of gene expression profiles between Gbm and Mm may provide additional clues about patterns associated with each tumor type.

Assignment of the 2.03 ppm resonance in in vivo 1H MRS of human brain tumour cystic fluid: contribution of macromolecules

MRI and MRS are established techniques for the evaluation of intracranial mass lesions and cysts. The 2.03 ppm signal recorded in their 1H-MRS spectra is often assigned to NAA from outer volume contamination, although it has also been detected in non-infiltrating tumours and large cysts. We have investigated the molecular origin of this resonance in ten samples of cystic fluids from human brain tumours. The NMR detected content of the 2.03 ppm resonance in 136 ms echo time spectra, assuming an N- CH3 origin, was 3.19 ± 1.01 mM. Only one third (34 ± 12%) of the N-acetyl containing compound (NAC) signal could be extracted by perchloric acid (PCA) indicating that most of it originated in a macromolecular PCA-insoluble component. Chemical analysis of the cyst fluids showed that sialic acid bound to macromolecules would account for 64.3% and hexuronic containing compounds for 29.2% of the NMR-detectable ex vivo signal, 93.4% of the signal at TE 136 ms. Lactate content measured by NMR (6.4 ± 4.4 mM) and the predominance of NAC originating in sialic acid point to a major origin from tumour rather than from plasma for this 2.03 ppm resonance.

Surgical versus conservative treatment in patients with cerebral cavernomas and non refractory epilepsy

PURPOSE The optimal therapy of patients with cerebral cavernoma (CCs) and new onset epilepsy, sporadic seizures, or non well established refractory epilepsy is still not clear. The aim of this study was to compare the incidence of seizures in patients with CCs both operated and non operated, in order to obtain more information on the correct management of these patients. MATERIALS AND METHODS We studied retrospectively 43 patients with non refractory epilepsy secondary to CCs. Twenty-six of them (60.5%) underwent surgery and made up the surgical group, and 17 patients were treated medically and constituted the medical group. Seizure frequency and other clinical variables were compared between both groups. RESULTS At two years, out of the 26 operated patients, 19 (73%) remained seizure free, 4 (15%) had less than a seizure per month, and one patient (4%) had more than one seizure per month. At five years, 15 patients of the surgical group remained for analysis. Of them, 11 (73.3%) were seizure free, and 4 (26.7%) had less than one seizure a month. In the medical group, 12 out of 17 patients were seizure free (70.6%). There were no significant differences between the two groups (p=0.2 and p=0.3, respectively). Seven patients had postoperative neurological sequelae. CONCLUSION Surgical treatment of patients with non refractory epilepsy due to CCs did not significantly reduce the likelihood of seizures when compared to medical treatment. It must also be considered that surgery carries serious risks. A prospective and randomized study must be carried out to further clarify our findings.

Development of a Predictor for Human Brain Tumors Based on Gene Expression Values Obtained from Two Types of Microarray Technologies

Development of molecular diagnostics that can reliably differentiate amongst different subtypes of brain tumors is an important unmet clinical need in postgenomics medicine and clinical oncology. A simple linear formula derived from gene expression values of four genes (GFAP, PTPRZ1, GPM6B, and PRELP) measured from cDNA microarrays (n = 35) have distinguished glioblastoma and meningioma cases in a previous study. We herein extend this work further and report that the above predictor formula showed its robustness when applied to Affymetrix microarray data acquired prospectively in our laboratory (n = 80) as well as publicly available data (n = 98). Importantly, GFAP and GPM6B were both retained as being significant in the predictive model upon using the Affymetrix data obtained in our laboratory, whereas the other two predictor genes were SFRP2 and SLC6A2. These results collectively indicate the importance of the expression values of GFAP and GPM6B genes sampled from the two types of microarray technologies tested. The high prediction accuracy obtained in these instances demonstrates the robustness of the predictors across microarray platforms used. This result would require further validation with a larger population of meningioma and glioblastoma cases. At any rate, this study paves the way for further application of gene signatures to more stringent biopsy discrimination challenges.

Papillary tumor of the pineal region

Tumors of the central nervous system (CNS) demonstrating papillary features, and particularly in the pineal region, are rare. Papillary tumor of the pineal region (PTPR) is a recently described rare neuroepithelial tumour included in the fourth edition of the World Health Organization (WHO) classification of tumours of the CNS, published in 2007. This new histopathological entity manifests in children and adults, with magnetic resonance (MR) imaging showing variable degree of T1 hyperintensity signal as well as contrast enhancement. In addition to the initial report of six cases by Jouvet et al. (Am J Surg Pathol 27:505–512, 2003) several case reports have been published in the literature to date. PTPR is characterized by presenting an epithelial-like cytology and a papillary architecture with immunoreactivity for broad-spectrum cytokeratins. Ultrastructurally observed features suggest ependymal differentiation and a possible origin from specialized ependymal cells of the subcommissural organ (SCO) has been postulated. The differential diagnosis of PTPR include pineal parenchymal tumors, choroid plexus tumors, papillary ependymoma, papillary meningioma, and metastasis. As a result of the rarity of these tumors, the biological behaviour of PTPR is not yet clear. It may correspond to WHO grades II or III. The high risk of local recurrence makes accurate surgery followed by radiotherapy necessary to achieve optimal treatment.