On the classification of cerebral tumors: A tribute to Leonid Smirnov.

The corresponding member of the Academy of Medical Sciences of the USSR Professor Leonid Iosifovich Smirnov (1889 - 1955) authored several dozen publications on neuropathology of infections, schizophrenia, cerebral injuries, and brain tumors. Based on his study of pathology of gunshot head injuries during World War II he suggested a doctrine of traumatic on traumatic brain disease. He was the author of the first Russian classification of cerebral tumors and had an impact on the development of neurooncology in the former USSR. The aim of this paper is to show the early development of modern neuropathology at the example of a leading Soviet neuropathologist in the first half of the 20th century and his relevance for modern classification of CNS tumors.

Management of craniofacial chondroid tumors.

BACKGROUND: Craniofacial chondroid tumors (CFCTs) constitute less than 1% of all intracranial mass lesions. No protocol for evaluation and management of CFCTs is developed at the moment. MATERIALS AND METHODS: We analyzed 51 patients with CFCTs operated on in Burdenko Neurosurgical Institute from 1980 until 2012, which included chondroma (15), chondroblastoma (3), chondromyxoid fibroma (11), and chondrosarcoma (22). Age varied from 2 to 76 years (mean, 40 y); the series included 23 women and 28 men. All tumors were divided into 4 groups: midline unilateral (8),midline bilateral (21), anterolateral (19), and lateral (3). This division was based on differences in surgical approaches (P = 0.009). RESULTS: All patients underwent surgical treatment. Complete removal was achieved in 20; subtotal, in 21; and partial, in 10. Two patients died, and early complications were observed in 10 cases. Early outcomes correlated with the benign nature of the tumors (P = 0.002). Follow-up data were available in 22 patients. Fifteen of 51 patients were reoperated on because of recurrence (a total of 43 reoperations were performed). The mean recurrence-free period was 45 months. In 3 patients, the tumor metastasized, and malignant transformation was observed in 3 cases. Sixteen patients received postoperative radiation therapy. Delayed sequelae occurred in 5 observations, and 5 patients died during long-term follow-up. Three-year survival in benign and malignant tumors was 87.5% and 55.6%, respectively, and 5-year survival was 83.3% and 40.0%, respectively. CONCLUSION: Surgical resection is the mainstay in treatment of both benign and malignant craniofacial tumors, and adjuvant radiation therapy is mandatory in malignant lesions; however, it should be avoided in benign lesions.

Pineal cyst management: A single-institution experience spanning two decades.

Background: Pineal cysts (PCs) are benign lesions commonly found on intracranial imaging. Despite their high prevalence, there is no clear consensus on the most appropriate management of patients with PCs, especially those with symptomatic nonhydrocephalic cysts. Methods: A retrospective analysis was performed on 142 patients with PCs (103 surgical cases and 39 conservatively managed cases). Data were examined, including clinical presentation, imaging findings, ophthalmological status, natural course, postoperative outcomes, and complications. Results: Surgical group: the most common symptom was headache (92%), followed by signs of intracranial hypertension due to hydrocephalus (22%). New radiological feature of PCs was found in 11 patients. From 71 patients with long-term follow-up, headache completely resolved in 44 (62%) patients; marked improvement was observed in 20 (29%); in 7 (9%) - headache remained unchanged. The most common postoperative complication was neuro-ophthalmological disorders (23%), with a tendency for resolution in the long-term follow-up period. Neuro-ophthalmological symptoms at last follow-up included upward gaze palsy (6%) and skew deviation (5%), followed by convergence disorders (3%) and eyelid-retraction (2%). Natural course group: PC size remained stable in 34 (87%) patients during the follow-up period. The patient's gender or age was not a significant predictor of cyst growth (P = 0.4, P = 0.56). Conclusion: The majority of patients with a newly diagnosed PC remain clinically and radiologically stable. Patients with nonhydrocephalic PCs and intractable headaches experience significant relief in headache symptoms, but are at risk of mild to moderate neuro-ophthalmological disorders. The natural course of PCs and factors promoting their growth still remains poorly defined.

Multiple hippocampal transections for mesial temporal lobe epilepsy.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of multiple hippocampal transections (MHT) in the treatment of drug-resistant mesial temporal lobe epilepsy. METHODS: Six patients underwent MHT at Burdenko Neurosurgery Center in 2018. The age of the patients varied from 18 to 43 years. All patients suffered from refractory epilepsy caused by focal lesions of the mesial temporal complex or temporal pole in dominant side. Postoperative pathology revealed neuronal-glial tumors in two patients, focal cortical dysplasia (FCD) of the temporal pole - in two patients, cavernous angioma - in one patient, and encephalocele of the preuncal area - in one patient. RESULTS: All patients underwent surgery satisfactorily. There were no postoperative complications except for homonymous superior quadrantanopia. This kind of visual field loss was noted in four cases out of six. During the follow-up period five patients out of six had Engel Class I outcome (83.3%). In one case, seizures developed after 1 month in a patient with FCD in the uncus (Engel IVA). After surgery, three out of six patients developed significant nominative aphasia. Two patients relative to the preoperative level demonstrated improvement in delayed verbal memory after MHT. Two patients showed a decrease level in delayed verbal memory. In preoperative period, visual memory was below the normal in one patient. Delayed visual memory in two cases impaired compared to the preoperative level. CONCLUSION: MHT can be considered as an effective method of drug-resistant mesial temporal lobe epilepsy caused by tumors of the medial temporal complex. At the same time, MHT makes it possible to preserve memory in patients with structurally preserved hippocampus. However, MHT do not guarantee the preservation of memory after surgery.

[Changes in the morphological structure of giant prolactinoma during treatment with cabergoline].

Currently, cabergoline therapy is the main method of treatment with prolactin. The use of the drug in most cases leads to tumor regression, normalization of prolactin levels and restoration of gonadotropic function. The mechanism of its impact on tumor cells in vivo, which is dynamically traced in the same human tumor, is the case of considerable interest. We observed a 30-year-old patient who was operated on twice for a giant prolactinoma before and on treatment by cabergoline. The morphological study after the first surgery (before introducing of cabergoline therapy) revealed a prolactin-positive pituitary tumor with a Ki-67 labeling index of 8% and with strong expression of dopamine type 2 receptors (D2R), CD31 and CD34. After 4 months, during which the patient received cabergoline at a dose starting from 0.5 mg to 1.5 mg per week, a second transsphenoidal surgery was performed with subtotal removal of residual tumor tissue. During the morphological study of the second biopsy sample, the tumor retained a pronounced immunopositivity to prolactin and D2R, with a decrease in the labeling index Ki-67 to 2%, as well as a decrease in the expression of CD31 and CD34. Subsequent cabergoline therapyresulted in persistent normoprolactinemia, restoration of androgen (and reproductive) status, and no tumor recurrence over a 10-year period on cabergoline treatment. Thus, one of the mechanisms of effect of cabergoline that leads to tumor regression is a decrease in the proliferative index and angiogenesis of the tumor.

Study of Simple Immunohistochemical Cytocolorimetric Assay Application for More Accurate Assessment of Prognosis in Patients with Pituitary Adenomas.

BACKGROUND: Immunohistochemistry is a basic diagnostic technique. Immunohistochemical examination results reflect mainly qualitative and less quantitative characteristics of proteomic status of cells. A combined approach with complex quantitative evaluation of marker expression using colorimetric analysis and computer technologies can expand the diagnostic capabilities of immunohistochemistry. We studied such an approach developed by using expression of the proliferative marker Ki-67 in pituitary adenomas. METHODS: A retrospective, blind, randomized, comparative study was performed of Ki-67 expression activity in pituitary adenomas using the traditional Ki-67 labeling index and a simple immunohistochemical cytocolorimetric analysis developed by us with immunohistochemical cytocolorimetric index (ICI) estimation as predictors of relapse, assessing the relationships of these indicators with the time before relapse. RESULTS: Mean Ki-67 labeling index was 3.87% ± 0.29% in the relapse-free group and 4.01% ± 0.29% in the relapse group; the difference was not statistically significant. The average Ki-67 ICI was 24.16% ± 0.51% in the relapse-free group and 30.68% ± 0.64% in the relapse group; the difference was statistically significant. The correlation coefficient of ICI values and time before relapse was -0.302, indicating the presence of a weak negative correlation. CONCLUSIONS: We successfully tested an ICI estimation method developed by us to assess Ki-67 expression in pituitary adenomas. The ICI technique can be used both as a prognostic factor for relapse and, in combination with other modern proteomic and genetic methods, as the basis for creation of new multimodal analyzing systems for functional state assessment of cells and tissues.

A Rare Case of Brain Angiolipoma Imitating Arteriovenous Malformation: Differential Diagnosis, Surgical Treatment, and Literature Review.

BACKGROUND: Angiolipomas are mesenchymal tumors composed of mature adipocytes with abnormal vascular elements. They are most commonly found in subcutaneous tissues of the trunk and are rarely seen at craniospinal axes. CASE DESCRIPTION: We present an untypical case of frontal lobe angiolipoma manifested with seizures and initially described as an arteriovenous malformation. CONCLUSION: MRI with fat-suppression sequence plays key role in angiolipomas diagnostics.

Spontaneous Transformation of Vestibular Schwannoma into Malignant Peripheral Nerve Sheath Tumor.

Although radiosurgery-induced transformation of vestibular schwannoma (VS) into malignant peripheral nerve sheath tumor (MPNST) is being widely discussed, little attention is paid to the spontaneous transition of these tumors. Although the pathogenesis of this phenomenon remains uncertain, growing number of reported cases might call to notice them. We present a case of a 29-year-old woman who suffered right-sided hearing loss which remained untreated for 4.5 years. Magnetic resonance imaging revealed a right cerebellopontine tumor and the patient underwent tumor removal through retrosigmoid approach. Pathologically, the tumor was benign acoustic schwannoma with increased Ki-67 8%-10%. The tumor relapsed only 6 months later and was removed again-this time it was malignant peripheral nerve sheath tumor MPNST. The patient was treated with stereotactic radiotherapy, but despite that tumor growth was observed again and she underwent the third operation. Later on, tumor progression was noted with multiple intraaxial metastases and patient died 17 months after the diagnosis of MPNST had been confirmed. This is a seventh documented case of spontaneous transformation of VS into MPNST, which is clinically important for recording.

DNA topoisomerase II-alpha and cyclin A immunoexpression in meningiomas and its prognostic significance: an analysis of 263 cases.

CONTEXT: Routine pathologic examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Therefore, numerous efforts have been made to evaluate the meningioma growth fraction and its prognostic value. However, a universally applicable proliferative marker for meningioma outcome is not yet a reality. OBJECTIVE: To investigate the prognostic utility of 3 proliferative markers, namely, Ki-67, DNA topoisomerase II-alpha (topoII), and cyclin A in a representative series of intracranial meningiomas. DESIGN: Two hundred sixty-three adult patients with intracranial meningiomas (208 benign, 42 atypical, and 13 anaplastic) were studied retrospectively. Tumor specimens were immunohistochemically examined with antibodies to Ki-67 (MM-1), topoII, and cyclin A. A computerized color image analyzer was used to count immunostained nuclei. RESULTS: The topoII and cyclin A scores exhibited a close correlation with Ki-67 immunostaining. Significant differences between the indices for all 3 markers were noted among the 3 grades of meningiomas. The scores for all 3 markers were significantly different between recurrent and nonrecurrent meningiomas, including benign tumors that were treated with gross total resection. Recurrence-free survival was significantly reduced for cases with a Ki-67 labeling index (LI) of 4.4% or greater, a topoII LI of 3.2% or greater, and a cyclin A LI of 3.1% or greater. Multivariate analysis revealed that the risk of recurrence for the entire meningioma cohort was significantly associated with tumor grade (hazard ratio = 2.7; P =.004), topoII LI of 3.2% or greater (hazard ratio = 5.5; P <.001), and a cyclin A LI of 3.1% or greater (hazard ratio = 2.4; P =.01). CONCLUSIONS: There is a close correlation in the expression of these 3 proliferative markers in meningiomas, and all of the markers showed a significant association with tumor grade, recurrence rate, and recurrence-free survival. Consequently, in addition to Ki-67, immunoexpression of topoII and cyclin A is available for predicting meningioma recurrence. Moreover, the topoII and cyclin A staining scores were found to be more sensitive predictors for meningioma progression than Ki-67 and, therefore, either of these 2 markers may prove to be clinically informative and useful.

Analysis of expression of microRNAs and genes involved in the control of key signaling mechanisms that support or inhibit development of brain tumors of different grades.

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNA molecules involved in the regulation of key biological processes. Different miRNAs with pro-oncogenic and anti-oncogenic properties have been identified in glioblastomas. We decided to analyze expression profiles of 10 mature miRNAs (miR-7-1, miR-10а, miR-17, miR-20а, miR-21, miR-23а, miR-26а, miR-137, and miR-222) in post-surgery glioma specimens of different grades in order to find whether the expression level correlates with tumor grades. We also measured expression of six key genes such as PTEN, p21/CDKN1A, MDR1, ABCG2, BAX, and BCL-2 involved in the regulation of critical glioma signaling pathways to establish the effect of miRNAs on these signaling mechanisms. METHODS: Using RT-PCR, we performed expression analysis of 25 tumor fresh samples (grades II-IV). RESULTS: We found gradual increase in miR-21 and miR-23a levels in all tumor grades whereas miR-7 and miR-137 were significantly down-regulated depending on the glioma grade. MDR, ABCG2, and p21/CDKN1A levels were significantly up-regulated while expression of PTEN was down-regulated in tumor samples compared to the normal brain tissue. CONCLUSIONS: These observations provide new insights into molecular pathogenic mechanisms of glioma progression and suggest about a potential value of miRNAs as a putative diagnostic marker of brain tumors.

Partial disconnection procedure in a patient with bilateral lesions (case report).

PURPOSE: The method of temporal lobectomy and parietooccipital disconnection has been applied in the treatment of patients with monolateral widespread cortical lesions and with hand motor function intact. There are no data regarding the use of this method in the treatment of patients with bilateral lesions. CASE REPORT: A case history of a 15-year-old female patient with medically refractory epilepsy is presented. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia associated with cortical dysplasia (CD) in the right temporo-parietal region. The left hemisphere had no signs of CD. Invasive monitoring revealed rhythmic theta-delta activity during the interictal period and fast activity during the ictal onset in the right temporal and parietal regions. The surgery procedure consisted of anterior temporal lobectomy, the removal of the right heterotopy nodus, the dissection of the posterior part of the corpus callosum, and the detachment of the temporo-parieto-occipital complex by dissection behind the sensorimotor cortex. Histological examination of the cortex revealed CD type I. The patient has been seizure-free for 4 years after surgery. CONCLUSION: Partial disconnection procedures may be effective in cases where total hemispherotomy is not indicated in patients with bilateral lesions and a well-lateralized epileptogenic zone localized in the temporo-parieto-occipital region.

Extradural spinal cord hemangioblastoma: a case report and literature review / Hemangioblastoma extradural medular: relato de caso e revisão de literatura / Hemangioblastoma extradural de la médula espinal: informe de un caso y revisión de la literatura

ABSTRACT Objective: Hemangioblastoma is a rare vascular sporadically occurring CNS tumor that can be associated with von Hippel-Lindau disease. Hemangioblastomas account for 2-6% of all spinal cord neoplasms and rank third among intramedullary space-occupying lesions. Methods: This was the first time in our practice that we had dealt with paravertebral hemangioblastoma with the sandglass growth pattern. The world literature describes only 3 case of a tumor with this growth pattern. Surgical and diagnostic aspects of patient treatment are considered. Results: During the operation, we adhered to the following stages: localization of the feeding vessel and of the poles of the tumor, surface dissection of the tumor, en bloc resection of the tumor, and hemostasis of the tumor cavity. Conclusions: Hemangioblastoma of extradural localization is a very rare pathology. However, when MRI signs characteristic of a vascular lesion are identified, it is necessary to carry out additional examinations, which may include CT perfusion study and, if required, selective angiography. Level of Evidence 5; Case report.

RESUMO Objetivos: Hemangioblastoma é um tumor vascular raro do SNC, que ocorre esporadicamente e pode ser associada à doença de Von Hippel-Lindau. Hemangioblastomas são responsáveis por 2-6% de todas as neoplasias da medula espinal e na terceira posição entre lesões, ocupando espaço intramedulares da medula espinal. Métodos: Foi a primeira vez em nossa prática que lidamos com hemangioblastoma paravertebral com o padrão de crescimento ampulheta. As fontes da literatura mundial descrevem apenas 3 casos de um tumor com esse padrão de crescimento. Aspectos cirúrgicos e diagnósticos de tratamentos do paciente são considerados. Resultados: Durante a operação, aderiu-se às seguintes fases: o recipiente de alimentação foi encontrado, os pólos do tumor foram encontrados, a dissecação da superfície do tumor foi feita, o tumor foi removido por um único bloco e a hemostasia da cavidade do tumor foi realizada. Conclusões: Hemangioblastoma de localização extradural é uma patologia muito rara, no entanto, quando sinais de MRI característicos de uma lesão vascular são identificados, o que é necessário para levar a cabo um exame suplementar, o qual pode incluir o estudo de perfusão CT e, se necessário, angiografia seletiva. Nível de Evidência V; Relato de caso.

RESUMEN Objetivo: El hemangioblastoma es un tumor vascular raro del SNC que ocurre esporádicamente y que puede asociarse con la enfermedad de von Hippel-Lindau. Los hemangioblastomas representan el 2%-6% de todas las neoplasias de la médula espinal y están en el tercer lugar entre las lesiones intramedulares que ocupan espacio. Métodos: Esta fue la primera vez en nuestra práctica que tratamos el hemangioblastoma paravertebral con patrón de crecimiento de reloj de arena. La literatura mundial describe solo tres casos de un tumor con este patrón de crecimiento. Se consideran aspectos quirúrgicos y de diagnóstico del tratamiento del paciente. Resultados: Durante la operación, elegimos las siguientes etapas: localización del vaso de irrigación y de los polos del tumor, disección superficial del tumor resección en bloque del tumor y hemostasia de la cavidad tumoral. Conclusiones: El hemangioblastoma de localización extradural es una patología muy rara. Sin embargo, cuando se identifican signos característicos de lesión vascular en la RM, es necesario realizar exámenes adicionales, que pueden incluir estudio de perfusión por TC y, si es necesario, una angiografía selectiva. Nivel de Evidencia V; Reporte de caso.

Immunohistochemical analysis of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in 271 meningiomas correlation with tumor grade and clinical outcome.

Routine pathological examination cannot distinctively predict the clinical course of meningiomas because even histologically benign tumors may recur after gross total resection. Numerous efforts have been made for the evaluation of different immunohistochemical assays in meningioma prognosis. We investigated the prognostic significance of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression by immunohistochemical analysis of 271 meningiomas. All tumors were additionally stained for the proliferation markers Ki-67 and DNA topoisomerase II alpha (TopoIIalpha). Significant differences between the number of p16INK4a-, p18INK4c- and p21CIP1-positive cases were noted among the 3 grades of meningiomas. p16INK4a- and p21CIP-positive tumors were found to prevail among benign meningiomas, whereas p18INK4c immunostaining was closely associated to anaplastic meningiomas. The number of p16INK4a- and p21CIP-positive cases was significantly lower in the cohort of recurrent meningiomas. In contrast, p18INK4c-positive cases were clustered among recurrent meningiomas regardless of tumor grade. Immunoreactivity of p14ARF, p27KIP1 and p73 did not show any differences between meningiomas of various histology and clinical outcomes. Multivariate analysis revealed that only tumor grade and TopoIIalpha index are independent criteria for predicting meningioma recurrence. Thus, the immunohistochemical assessment of p16INK4a, p14ARF, p18INK4c, p21CIP1, p27KIP1 and p73 expression in meningiomas does not appear to provide prognostically useful information. Further studies are needed to identify more reliable prognostic markers and to address in more detail the role of cell cycle aberrations in these tumors.