Pathomorphological Diagnostic Criteria for Focal Cortical Dysplasias and Other Common Epileptogenic Lesions-Review of the Literature.

Focal cortical dysplasia (FCD) represents a heterogeneous group of morphological changes in the brain tissue that can predispose the development of pharmacoresistant epilepsy (recurring, unprovoked seizures which cannot be managed with medications). This group of neurological disorders affects not only the cerebral cortex but also the subjacent white matter. This work reviews the literature describing the morphological substrate of pharmacoresistant epilepsy. All illustrations presented in this study are obtained from brain biopsies from refractory epilepsy patients investigated by the authors. Regarding classification, there are three main FCD types, all of which involve cortical dyslamination. The 2022 revision of the International League Against Epilepsy (ILAE) FCD classification includes new histologically defined pathological entities: mild malformation of cortical development (mMCD), mild malformation of cortical development with oligodendroglial hyperplasia in frontal lobe epilepsy (MOGHE), and "no FCD on histopathology". Although the pathomorphological characteristics of the various forms of focal cortical dysplasias are well known, their aetiologic and pathogenetic features remain elusive. The identification of genetic variants in FCD opens an avenue for novel treatment strategies, which are of particular utility in cases where total resection of the epileptogenic area is impossible.

Immunohistochemical characteristics of brain metastases and corresponding primary lung cancer.

PURPOSE: to study brain metastases (BM) and their corresponding primary lung cancers (LCs). METHODS: Surgically resected BMs and their corresponding primary LCs from 30 patients (25 men, 83%; age 55±9 years) were studied: 21 adenocarcinomas (ACs), 5 squamous cell carcinomas (SCCs), 4 small cell lung carcinomas (SCLCs). The histological subtype, immunohistochemical expression of TTF1, p63, Ki67 (proliferative activity), CD31, number of intratumoral microvessels, (NIM) and survival were evaluated. RESULTS: There was a different histological structure in 47% of the cases of ACs of the lung in comparison with the corresponding metastasis, but none in SCC and SCLC. TTF-1 was expressed in a greater number of ACs (n=20; 95%), with lower mean expression levels, while the corresponding BM expressed the marker less frequently (n=16;76%) with higher mean expression values (p=0.011). P63 was expressed in all SCCs (p=0.68). Cytokeratin 7 was expressed equally in all ACs. Ki-67 proliferative index (PI) was higher in SCLC than in AC (p=0.008), in SCLC BM than in AC BM (p<0.001), and in SCLC BM than in SCC BM (p=0.008). The Ki-67 PI in BM was higher than in AC (p=0.003), SCC (p=0.048), but without difference in SCLC (p=0.141). CD31 NIM was higher in AC than in SCLC (p=0.003), in SCC than in SCLC (p=0.009), while no difference between AC and SCC was found (p=0.467). There were no differences between LC/BM in the NIM. Survival after surgery for LC was significantly longer in AC than in SCLC (p=0.017). SCLC histology and Ki67>18% were established as negative prognostic factors after surgery for LC. Such factors were not found after surgery for BM. CONCLUSION: There are differences between primary LC and corresponding BM - in histology, immunohistochemical expression and proliferative activity, but there are no significant differences in vascularization. SCLC histology and Ki67>8% may represent negative prognostic factors after surgery for LC with BM.

Mesenchymal Stem Cells Derived and Cultured from Glioblastoma Multiforme Increase Tregs, Downregulate Th17, and Induce the Tolerogenic Phenotype of Monocyte-Derived Cells.

Mesenchymal stem cells (MSCs) possess immunosuppressive properties and have been described in the tumor microenvironment of glioblastoma multiforme (GBM). This manuscript has two major topics-first, to describe isolated and cultured MSCs derived from GBM (GB-MSCs) and second, to examine their in vitro immunosuppressive capacity. Our results display cells with morphology and phenotype, clonogenic ability, and osteogenic potential, typical for MSCs. Furthermore, the cultured cells show intracellular expression of the neural markers Nestin and GFAP. They express PD-L1 and secrete TGFß, CCL-2, PGE2, IL-6, and sVEGF. Coculturing of GB-MSCs with PBMCs isolated from healthy donors results in a decreased percentage of Th17 lymphocytes and an increased percentage of Tregs. Regarding the impact of GB-MSCs on monocytes, we establish an augmented expression of CD14 and CD86 along with diminished expression of HLA-DR and CD80, which is associated with tolerogenic phenotype monocyte-derived cells. In conclusion, our results describe in detail GBM-derived and cultured cells that meet the criteria for MSCs but at the same time express Nestin and GFAP. GB-MSCs express and secrete suppressive molecules, influencing in vitro T cells and monocytes, and are probably another factor involved in the immune suppression exerted by GBM.

Optic Nerve Glioma in Two Sisters with Family History of Neurofibromatosis Type 1.

Optic nerve glioma (ONG) is associated in 10% of patients with neurofibromatosis (NF) type 1. To date no consensus has been reached regarding the therapeutic approach and prevention of visual impairment in these patients. Reports in the literature vary from a conservative approach (observation) to the use of single treatment modalities or multimodality protocols of surgical removal, radiotherapy, and/or chemotherapy. We present our experience with two siblings with ONG whose mother carries cutaneous stigmata of NF type 1. The younger sister was diagnosed 3 years after the treatment of the older sibling following recommended imaging for screening. Postoperative follow-up for 11 and 15 years, respectively, demonstrated lack of tumor regrowth and preserved vision in the contralateral eye. We discuss the treatment strategy in pediatric patients with orbital ONG associated with NF type 1.

Cultured Cells Isolated from CNS Indolent B-Cell Lymphoma Have Characteristics of Mesenchymal Stem Cells: A Clinical Case and Scientific Research.

The case report presented here describes the culturing and characterization of mesenchymal stem cells (MSCs) isolated from a primary indolent B-cell lymphoma, located in the CNS of an immunocompetent patient. The presence of such cells in the tumor mass can further elucidate the pathogenesis of the disease and reveal possible future approaches for its treatment. We present a case report of a 61-year-old immunocompetent woman who had an episode of confusion with numbness in the right leg and the right arm, slurred and dysarthric speech and urine incontinence. The peripheral blood tests were normal. The neurological examination demonstrated a latent hemi-paresis of the right side, aphasia, discrete hypertension and bradypsychia. The ophthalmologic examination revealed left quadranopsia. Computed tomography and magnetic resonance imaging of the brain showed a 3.5 × 2.9 cm infiltrative neoplastic lesion involving the left temporal parenchyma. The morphological features and the immunophenotyping of the lymphoid cell composition were consistent with low-grade (indolent) B-lymphocyte non-Hodgkin's lymphoma of CNS. Cells, isolated from the resected tumor mass, were cultured in vitro in medium containing 10% fetal bovine serum (FBS) and characterized by their morphology, growth, phenotype, clonogenicity and osteogenic differentiation. It was apparent that the cultured cells isolated from the indolent B- cell lymphoma located in the CNS have the basic characteristics of mesenchymal stem cells. The presence of MSCs is described for the very first time in such type of tumor. The well-known immunosuppressive properties of the MSCs may represent another mechanism favouring the tumor growth.

Metachronous Development of Meningothelial Meningioma, Basal Cell Carcinoma, and Glioblastoma Multiforme in a Patient with Pancreatic Incidentaloma.

We report the unique case of a 61-year-old male patient with known pancreatic incidentaloma who additionally developed 3 other histologically different tumors: left sphenoid wing meningothelial meningioma, basal cell carcinoma of the occiput, and right occipital lobe glioblastoma multiforme. The latter were totally removed with a favorable clinical outcome. The patient's family history was unremarkable, and no data on any previous head and neck irradiation were found.

Infrared Thermography in Surgery of Newly Diagnosed Glioblastoma Multiforme: A Technical Case Report.

Infrared thermography (IRT) is a real-time non-contact diagnostic tool with a broad potential for neurosurgical applications. Here we describe the intraoperative use of this technique in a single patient with newly diagnosed glioblastoma multiforme (GBM). An 86-year-old female was admitted in the clinic with a 2-month history of slowly progressing left-sided paresis. Neuroimaging studies demonstrated an irregular space-occupying process consistent with a malignant glioma in the right fronto-temporo-insular region. An elective surgical intervention was performed by using 5-aminolevulinic acid fluorescence (BLUE 400, OPMI) and intraoperative IRT brain mapping (LWIR, 1.25 mRad IFOV, 0.05°C NETD). After dura opening, the cerebral surface appeared inconspicuous. However, IRT revealed a significantly colder area (Δt° 1.01°C), well corresponding to the cortical epicenter of the lesion. The underlying tumor was partially excised and the histological result was GBM. Intraoperative IRT seems to be a useful technique for subcortical convexity brain tumor localization. Further studies with a large number of patients are needed to prove the reliability of this method in GBM surgery.

Cells isolated from human glioblastoma multiforme express progesterone-induced blocking factor (PIBF).

Glioblastoma multiforme (GBM) is the most common and malignant tumor in the central nervous system. One of the contemporary hypotheses postulates that its pathogenesis is associated with the cancer stem cells (CSCs) which originate from mutations in the normal neural stem cells residing in their specific "niches." Simultaneously with its aggressive development the tumor suppresses the local immune system by different secreted and/or cell expressed factors. Progesterone-induced blocking factor (PIBF) is an immunomodulatory protein with known role in the regulation of the immune response in the reproductive system. Expression of PIBF has been described in some tumors as one of the factors suppressing the anti-tumor immunity. The aim of the present study was to check for the expression of PIBF from cells isolated from six GBMs. To characterize the cultured cells and to study the PIBF expression confocal microscopy, flow cytometry, ELISA, and real-time PCR were used. The results obtained showed expression of markers typical for cancer CSCs and secretion of interleukin 6 by the GBM-derived cultured cells. The results convincingly prove that PIBF is intracellularly expressed by the cultured cells from the all six GBM samples, and this fact is confirmed by three different methods-flow cytometry, confocal microscopy, and real-time PCR. This paper reports for the first time the expression of PIBF by GBM-derived cells cultured in vitro and reveals a new aspect of the immunosuppressive mechanism used by GBM in escaping the immune control.

Chiari type II malformation: a case report and review of literature.

INTRODUCTION: Herniation of cerebellar vermis through the foramen magnum, internal hydrocephaly and spina bifida cystica are the major signs of Chiari type II malformation. Spina bifida cystica (1 in 2000 neonates) is very often the first clinical manifestation of the disease. AIM: To discuss the pathomorphology, clinical picture and possible treatment of this underestimated malformation. PATIENTS AND METHODS: Lumbosacral spina bifida aperta and flaccid paraplegia of the lower limbs were found in a female newborn. Later on, pneumonia and evidence of markedly expressed internal hydrocephaly were found. At 48 days of age, surgical correction of the meningocele was undertaken. There was a sudden heart and respiratory arrest at the end of surgery but in spite of the cardiopulmonary resuscitation the infant died 24 hours later. RESULTS: Postmortem pathological examination revealed expressed internal hydrocephaly, small posterior fossa, herniation of vermis and atrophic medulla oblongata; presence of these signs verified the Chiari type II malformation. It is very difficult to diagnose this malformation antemortem without magnetic resonance imaging. Brainstem dysfunction is the most common cause of death in children under 2 years of age with Chiari type II malformation. Its clinical manifestation can be episodic and poorly expressed. CONCLUSIONS: A thorough understanding of this entity (clinical and pathomorphological manifestations) and magnetic resonance imaging are mandatory for the malformation to be diagnosed. Early recognition of symptoms of brainstem compression and a subsequent surgical decompression can decrease the high mortality rate among children with Chiari type II malformation.