Viral oncogenesis in tumours of the central nervous system: reality or random association? A retrospective study on archived material.

Central nervous system (CNS) tumours have devastating effects and are recurrent, with dismal prognosis (gliomas) or life-threatening by the compression effect (meningiomas). This disease's aetiology remains debatable. Over the last decade, the hypothesis that human viruses may be implicated in these tumours has been proposed. In this study, our aim is to examine the presence of 11 viruses in the most frequent CNS primary tumours. Using polymerase chain reaction (PCR), we assessed the viral presence in archived, paraffin-embedded tumour tissues from 114 patients with glioma and meningioma and in the brain tissue from 40 controls lacking tumour pathology. We focused on candidate neuro-oncogenic types (herpesviridae and polyomaviruses) and on human papillomavirus (HPV). HPV presence, for which involvement in these tumours was hardly investigated, was found to be associated with both tumour categories compared with controls (glioma, p = 0.032; meningioma, p = 0.032), whereas the presence of the neuro-oncogenic viruses was found in a negligible number of both categories, suggesting a lack of association with the tumour presence. Moreover, our study reveals a positive correlation between HPV presence and glioma malignancy, and a negative correlation with meningioma grading. Our results suggest that the presence of HPV seems to be significantly associated with primary tumours of the CNS and its meninges.

Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Series of 14 Cases and Review of the Literature.

Solitary fibrous tumor (SFT) is a rare type of tumor characterized by spindle-shaped cells originating from mesenchymal tissue. This case series presents a collection of 14 intracranial solitary fibrous tumors treated between 2014 and 2022 in our institute in Bucharest, Romania. Through a systematic investigation, key aspects spanning the preoperative, intraoperative, and postoperative phases of patient care were highlighted. Our study examines various factors including tumor location (which was very heterogeneous), size (median of 49 mm, ranging between 22 mm and 70 mm), surgical techniques employed, and recurrence rates. The data was analyzed using Python version 3.10 (Python Software Foundation, Wilmington, Delaware, United States). Gender disparities in SFT were noted, particularly the male-to-female ratio which was 5:9. The use of the Medical Research Council (MRC) Scale for Muscle Strength aided in evaluating severity and postoperative outcomes. GTR was achieved in nine out of 14 cases (64.28%), prolonging the period of recurrence-free survival.

Brain metastases and multiple cerebral aneurysms from cardiac myxoma: case report and review of the literature.

Cardiac myxoma, the most common benign cardiac tumour, can determine brain metastases or multiple cerebral aneurysms, but very few cases of both complications have been reported. We discuss the therapeutic management in the case of a patient, operated for a cardiac myxoma, who presented three intracerebral tumours and five cerebral microaneurysms.

Esthesioneuroblastoma: the complete picture - case report and review of the literature.

Esthesioneuroblastoma (ENB), also called olfactory neuroblastoma, is a cancerous tumor originating from the olfactory neuroepithelial cells frequently invading the brain through the cribriform plate. The optimal therapy is the multimodality treatment involving a group of physicians trained in different medical specialties. Establishing a careful histopathological diagnostic and treatment planning based on a multidisciplinary approach is of paramount importance. The treatment of ENB correlates with the extent of the lesion, with surgery being the mainstay of therapy followed by postoperative irradiation. Surgery, when complete, image-verified and associated with radiation therapy results in long-term survival and presents a very low probability of illness recurrence. We present the case of a 46-year-old female with ENB, who was operated on in the Clinic of Neurosurgery of the National Institute of Neurology and Neurovascular Diseases in Bucharest, Romania, through a bifrontal craniotomy approach. Gross total resection of the intracranial extent was performed. The pathological diagnosis revealed an aggressive olfactory neuroblastoma. Three weeks after discharge from hospital, the tumor was completely resected through a lateral rhinotomy performed by an otorhinolaryngologist. Six weeks later, the patient received adjuvant therapy (radiotherapy and chemotherapy). The outcome was favorable, with no tumor recurrence at 20 months postoperatively. Our case demonstrates that even when dealing with a visibly aggressive tumor, a correct diagnosis, accurate classification and grading along with appropriate therapy ensure a favorable outcome.

Differential Intestinal Mucosa Transcriptomic Biomarkers for Crohn's Disease and Ulcerative Colitis.

Genetic research has shaped the inflammatory bowel disease (IBD) landscape identifying nearly two hundred risk loci. Nonetheless, the identified variants rendered only a partial success in providing criteria for the differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD). Transcript levels from affected intestinal mucosa may serve as tentative biomarkers for improving classification and diagnosis of IBD. The aim of our study was to identify gene expression profiles specific for UC and CD, in endoscopically affected and normal intestinal colonic mucosa from IBD patients. We evaluated a panel of 84 genes related to the IBD-inflammatory pathway on 21 UC and 22 CD paired inflamed and not inflamed mucosa and on age-matched normal mucosa from 21 non-IBD controls. Two genes in UC (CCL11 and MMP10) and two in CD (C4BPB and IL1RN) showed an upregulation trend in both noninflamed and inflamed mucosa compared to controls. Our results suggest that the transcript levels of CCL11, MMP10, C4BPB, and IL1RN are candidate biomarkers that could help in clinical practice for the differential diagnosis between UC and CD and could guide new research on future therapeutic targets.

Preferential Association of Lissencephaly-1 Gene Expression with CD133+ Glioblastoma Cells.

Lissencephaly-1 (Lis1) protein is a dynein-binding protein involved in neural stem cell division, morphogenesis and motility. To determine whether Lis1 is a key factor in glioblastoma, we evaluated its expression and function in CD133+ glioblastoma cells. Global, Lis1 gene expression is similar in glioblastoma and normal samples. Interestingly, immunohistochemistry data indicate increased Lis1 expression colocalized with CD133 in a subset of glioma cells, including the tumor cells with perivascular localization. Lis1 gene expression is increased up to 60-fold in CD133 positive cells isolated from primary cultures of glioblastoma and U87 glioblastoma cell line as compared to CD133 negative cells. To investigate the potential role of Lis1 in CD133+ glioblastoma cells, we silenced Lis1 gene in U87 cell line obtaining shLis1-U87 cells. In shLis1-U87 cell culture we noticed a significant decrease of CD133+ cells fraction as compared with control cells and also, CD133+ cells isolated from shLis1-U87 were two times less adhesive, migratory and proliferative, as compared with control transfected U87 CD133+ cells. Moreover, Lis1 silencing decreased the proliferative capacity of irradiated U87 cells, an effect attributable to the lower percentage of CD133+ cells. This is the first report showing a preferential expression of Lis1 gene in CD133+ glioblastoma cells. Our data suggest a role of Lis1 in regulating CD133+ glioblastoma cells function.

Immunohistochemical analysis of GFAP-δ and nestin in cerebral astrocytomas.

GFAP-δ, the delta isoform of the glial fibrillary acidic protein, is particularly expressed in the subventricular zone (SVZ) of the brain. GFAP-δ positive cells in the SVZ co-express the neural stem cells (NSCs) marker nestin. According to the theory of glioma oncogenesis, transformation of a cell population with stem features which resides in the SVZ could be the origin of astrocytomas. Moreover, it is known that cancer stem cells promote tumor invasion in cerebral astrocytomas. Therefore, we investigated the immunostaining of GFAP-δ and nestin in cerebral astrocytomas and evaluated the correlation between the positive cell ratio of these markers and the neuroimaging features associated with tumor invasion in forty-four cases of grade II, III and IV cerebral astrocytomas (World Health Organization's classification). Tissue samples were obtained by stereotactic biopsies in all cases. According to the preoperative neuroimaging criteria, tumors were categorized into highly invasive and low invasive. Most of the low-grade and high-grade astrocytomas express GFAP-δ and nestin. The positive cell ratio of GFAP-δ and the positive cell ratio of nestin were statistically significantly higher in highly invasive tumors compared with low-invasive tumors (p < 0.05). Altogether, these results suggest that GFAP-δ and nestin could be clinically relevant markers associated with tumor invasiveness in cerebral astrocytomas.

Adhesion cell molecules as potential markers of aggressiveness in meningiomas.

Routine histopathological criteria are poor predictors of the outcome in meningiomas. The present study tried to determine if some adhesion cell molecules could be helpful in assessing the histological aggressiveness in meningiomas of all grades. Our series comprised 113 cases, WHO grade I (n=53), WHO grade II (n=47) and WHO grade III (n=13). Three cases of meningeal non-meningothelial tumors (hemangiopericytoma, hemangioblastoma and fibrosarcoma) were also studied as control tissue. Immunohistochemistry for CD44, CD54, E-cadherin, progesterone receptor (PGR) and Ki67 was performed. CD54 was for the first time systematically assessed in meningiomas of all three grades of malignancy. CD44 and CD54 were expressed in 58.4 and 31.72% of cases, respectively. CD54 expression showed a direct correlation with the degree of histological anaplasia and Ki67 values. More than half of cases (58.11%) were negative for E-cadherin, mostly the anaplastic ones, which also showed less positive areas for this marker. Cell adhesion molecules were not significantly related to a particular histological type and proliferating potential of meningiomas. Overall, CD54 as well as E-cadherin could be used as additional aggressiveness indicators aside the classical ones. On the other way, Ki67 once again confirmed its significant role in the assessment of meningioma aggressiveness.

A rare tumor revealed by abdominal trauma: case presentation.

Pseudomyxoma peritonei is a rare and poorly understood form of disease characterized by mucin deposits in the peritoneum. The term includes a broad range of neoplasms with different patterns of evolution, from benign to borderline or even to malignant lesions. The disease may be asymptomatic until advanced stages. We present the case of a 65-year-old patient who presented for pain in the right hemiabdomen, after a trauma by falling from small height. Abdominal imaging studies oriented the diagnosis to a traumatic disease. At laparotomy, a mucinous tumor attached to the right colon was discovered. The main particularity of the case is that the origin of the pseudomyxoma could not be identified.

Angiogenic markers: molecular targets for personalized medicine in pituitary adenoma.

AIM: Pituitary adenomas are typically slow-growing and histologically benign tumors that can occasionally behave in a malignant-like manner, invading adjacent structures or recurring after treatment. Using protein analysis methods and multiplex xMAP assays, we aimed to find out if these particular types of tumors express angiogenic markers VEGF and basic FGF (bFGF), which are associated with tumor growth and invasiveness, and quantify them in order to establish their usefulness as biomarkers. MATERIALS & METHODS: We have analysed the expression of angiogenic markers VEGF and bFGF in serum and tissue specimens from 66 pituitary adenomas (43 invasive and 23 noninvasive). For serum analysis, we used xMAP and ELISA, and for tissue analysis, we performed histopathology and immunohistochemistry. RESULTS & CONCLUSION: We measured the serum angiogenic factors in pituitary adenomas. The quantification methods revealed significant differences between pituitary adenoma patients and controls, for both VEGF (212.4 vs 112.5 pg/ml in controls) and bFGF (mean value of 12.6 vs 10.8 pg/ml in controls), and also differentiated between invasive and noninvasive adenomas (p < 0.05). The tissue expression of VEGF and bFGF strongly correlated with their serum level increase. Our findings can be further developed into methods for selection of patients suitable for personalized, antiangiogenic therapy.

Pancreatic expression of DOG1: a novel gastrointestinal stromal tumor (GIST) biomarker.

The cDNA microarray gene profile of gastrointestinal stromal tumors (GISTs) revealed that DOG1 (TMEM16A) gene was mostly expressed in these neoplasms. Immunohistochemically, DOG1 protein was found positive in a significant proportion of GISTs. However, normal tissues' expression of DOG1 is not yet completely studied. Our study intended to identify the DOG1 protein expression in normal adult and fetal tissues, in comparison with that of GISTs, using an anti-DOG1 polyclonal serum. Fourteen CD117/CD34-positive GIST cases were tested for DOG1. Tissue samples from autopsies of 15 human fetuses and 11 adults were tested immunohistochemically on simple or double staining with antibodies raised against: DOG1, insulin, glucagon, somatostatin, NK1, PGP9.5, chromogranin A, and synaptophysin. All the tested GISTs were positive for DOG1, with a membranous and cytoplasmic location. The normal tissues showed a distinct positivity for DOG1 only in the endocrine pancreas, in both fetal and adult ones. The other tissues tested showed a weak or negative reaction. The DOG1 staining pattern in the pancreas islets was granular, like that of neuroendocrine markers. The location of DOG1 expression in pancreatic islets was partly similar to neuroendocrine markers chromogranin A, PGP9.5, and synaptophysin. The positive cells were situated centrally, in the vicinity of insulin-bearing cells as seen on double staining. DOG1 positivity in fetal and adult pancreatic islets suggests the strong antibody affinity for neuroendocrine cells. Before making a final conclusion regarding the suitability of DOG1 as a new neuroendocrine marker, a large survey of neuroendocrine lesions must be undertaken, including carcinoid tumors of various sites and pancreatic endocrine tumors. To the best of our knowledge, this particular localization has not been reported yet for DOG1.

Highly cystic brain tumor: rare histological features in an ependymoma.

Ependymoma is a slowly growing tumor appearing mostly in children and young adults. Several histological patterns are described. We report a case with unusual microscopic features, composed mostly of multiple cysts. Ultrastructural and immunohistochemical examination confirmed the diagnosis. Neuropathologists should be aware of this particular change which can generate some diagnostic difficulties.