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      Meninigiomas of the Craniocervical Junction – A Distinctive Subgroup of Meningiomas

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          Abstract

          Objective

          Meningioma of the cranio-cervical junction is a rare diagnosis and demand a thorough surgical planning as radical excision of these tumors is difficult. In this context recurrence is most likely due to regrowth of residual tumor. The aim of this study was to evaluate the clinical course of patients operated for craniocervical meningioma (CCM) and to investigate the histological features of these tumors and their impact on recurrence rate.

          Methods

          All patients who were operated for CCM at our institution between 2003 and 2012 were identified. Presenting symptoms, MRI findings, surgical approaches and recurrence rate were reviewed retrospectively using medical charts. Histological features of the included tumors were studied focusing on subtypes and MIB-1 immunoreactivity and compared with MIB-1 immunoreactivity in an age and gender-matched control group of patients with supratentorial meningioma.

          Results

          18 patients with CCM with a mean age of 56.2 years and median follow-up of 60 months were included in the study. Sensory or motor deficit was the most frequent presenting symptom followed by neck pain and lower cranial nerve palsy. Simpson grade II resection was achieved in 16 patients and Simpson grade III resection in two patients. Mortality, morbidity and recurrence rates were 16.7%, 5.5% and 5.5%, respectively. According to the WHO-grading all were found to be grade I meningiomas. Histological subtypes included meningotheliomatous (10), transitional (2), fibrillar (2), angiomatous (3) and secretory (1) meningioma. The mean MIB-1 labeling index in the study group was significantly higher than in the control group, (7.2% and 3.6%, respectively), p < 0.05. There was no correlation between MIB-1 levels and tumor recurrence.

          Conclusions

          CCM seems to have a benign character. Despite a significantly higher MIB-1 index, a high rate of recurrence was not observed. Therefore, approaches with high morbidity are not justified. Nevertheless, in view of the challenging approaches with limited access to the lesion, CCM should be considered a distinctive clinical subgroup.

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          Most cited references21

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          Histological classification and molecular genetics of meningiomas.

          Meningiomas account for up to 30% of all primary intracranial tumours. They are histologically classified according to the World Health Organization (WHO) classification of tumours of the nervous system. Most meningiomas are benign lesions of WHO grade I, whereas some meningioma variants correspond with WHO grades II and III and are associated with a higher risk of recurrence and shorter survival times. Mutations in the NF2 gene and loss of chromosome 22q are the most common genetic alterations associated with the initiation of meningiomas. With increase in tumour grade, additional progression-associated molecular aberrations can be found; however, most of the relevant genes are yet to be identified. High-throughput techniques of global genome and transcriptome analyses and new meningioma models provide increasing insight into meningioma biology and will help to identify common pathogenic pathways that may be targeted by new therapeutic approaches.
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            Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections.

            The monoclonal antibody Ki-67 reacts with a human nuclear cell proliferation-associated antigen that is expressed in all active parts of the cell cycle. Recently we have raised monoclonal antibodies, MIB 1-3, against recombinant parts of the Ki-67 antigen. These antibodies are true Ki-67 equivalents, as demonstrated by immunostaining of fresh specimens, biochemistry, and molecular biological techniques. Formalin-fixed, paraffin-embedded sections routinely processed for immunohistochemistry failed to stain for Ki-67 and MIB 2. Antibodies MIB 1 and MIB 3 labelled mitotic figures, while non-mitotic proliferating cells were negative under these conditions. However, when dewaxed microwave oven-processed paraffin sections of formalin-fixed tissues were used, MIB 1 and MIB 3 gave strong nuclear staining of those cells presumed to proliferate under a variety of normal and neoplastic conditions. Moreover, routine decalcification or depigmentation techniques did not alter the immunoreactivity of MIB 1 and MIB 3 with microwave-processed paraffin sections. This method is highly reproducible, easy to perform at low cost, and no additional technical skill is needed because after microwave treatment just routine immunohistochemical methods are used. Since we have successfully applied this new method to sections obtained from paraffin blocks stored for a long time (in one case more than 60 years), the assessment of cell kinetics through the detection of Ki-67 antigen is now possible on archival material collected in histopathology departments all over the world.
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              Significance of Simpson grading system in modern meningioma surgery: integration of the grade with MIB-1 labeling index as a key to predict the recurrence of WHO Grade I meningiomas.

              Techniques for the surgical treatment of meningioma have undergone many improvements since Simpson established the neurosurgical dogma for meningioma surgery in his seminal paper published in 1957. This study aims to assess the clinical significance and limitations of the Simpson grading system in relation to modern surgery for WHO Grade I benign meningiomas and to explore the potential of the cell proliferation index to complement the limitations in predicting their recurrence. The surgical records of patients who underwent resection of intracranial meningiomas at the University of Tokyo Hospital between January 1995 and August 2010 were retrospectively analyzed. The authors investigated the relationships between recurrence-free survival (RFS) and Simpson grade or MIB-1 labeling index value. A total of 240 patients harboring 248 benign meningiomas were included in this study. Simpson Grade IV resection was associated with a significantly shorter RFS than Simpson Grade I, II, or III resection (p<0.001), while no statistically significant difference was noted in RFS between Simpson Grades I, II, and III. Among meningiomas treated by Simpson Grade II and III resections, however, multivariate analysis revealed that an MIB-1 index of 3% or higher was associated with a significantly shorter time to recurrence. The clinical significance of the different management strategies related to Simpson Grade I-III resection may have been diluted in the modern surgical era. The MIB-1 index can differentiate tumors with a high risk of recurrence, which could be beneficial for planning tailored optimal follow-up strategies. The results of this study appear to provide a significant backing for the recent shift in meningioma surgery from attempting aggressive resection to valuing the quality of the patient's life.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                12 April 2016
                2016
                : 11
                : 4
                : e0153405
                Affiliations
                [1 ]Department of Neurosurgery, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
                [2 ]Institute of Neuropathology, Universitätklinikum Hamburg-Eppendorf, Hamburg, Germany
                Heinrich-Heine University, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: LD JM JR. Performed the experiments: LD JM. Analyzed the data: LD JM JR. Wrote the paper: LD TA JM PE MW JR.

                Article
                PONE-D-15-40415
                10.1371/journal.pone.0153405
                4829216
                27070421
                02ecfe99-c909-47d0-be02-9e9654ec646c
                © 2016 Dührsen et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 September 2015
                : 29 March 2016
                Page count
                Figures: 2, Tables: 0, Pages: 7
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Neurological Tumors
                Meningioma
                Medicine and Health Sciences
                Neurology
                Neurological Tumors
                Meningioma
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Medicine and Health Sciences
                Health Care
                Health Statistics
                Morbidity
                Medicine and Health Sciences
                Oncology
                Cancer Treatment
                Surgical Oncology
                Medicine and Health Sciences
                Clinical Medicine
                Clinical Oncology
                Surgical Oncology
                Medicine and Health Sciences
                Oncology
                Clinical Oncology
                Surgical Oncology
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Research and Analysis Methods
                Imaging Techniques
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Medicine and Health Sciences
                Radiology and Imaging
                Diagnostic Radiology
                Magnetic Resonance Imaging
                Biology and Life Sciences
                Physiology
                Sensory Physiology
                Somatosensory System
                Pain Sensation
                Medicine and Health Sciences
                Physiology
                Sensory Physiology
                Somatosensory System
                Pain Sensation
                Biology and Life Sciences
                Neuroscience
                Sensory Systems
                Somatosensory System
                Pain Sensation
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