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Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery. Uppsala Univ Hosp, Dept Neurosurg, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology. Univ Uppsala Hosp, Dept Neurol, Uppsala, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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2016 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 125, no 5, p. 1155-1166Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE Magnetic resonance imaging tends to underestimate the extent of diffuse low-grade gliomas (DLGGs). With the aim of studying the presence of tumor cells outside the radiological border, the authors developed a method of correlating MRI findings with histological data in patients with suspected DLGGs in whom en bloc resections were performed. METHODS Five patients with suspected DLGG suitable for en bloc resection were recruited from an ongoing prospective study. Sections of the entire tumor were immunostained with antibodies against mutated IDH1 protein (IDH1-R132H). Magnetic resonance images were coregistered with corresponding IDH1 images. The growth pattern of tumor cells in white and gray matter was assessed in comparison with signal changes on corresponding MRI slices. RESULTS Neuropathological assessment revealed DLGG in 4 patients and progression to WHO Grade III glioma in 1 patient. The tumor core consisted of a high density of IDH1-R132H-positive tumor cells and was located in both gray and white matter. Tumor cells infiltrated along the peripheral fibers of the white matter tracts. In all cases, tumor cells were found outside the radiological tumor border delineated on T2-FLAIR MRI sequences. CONCLUSIONS The authors present a new method for the coregistration of histological and radiological characteristics of en bloc-removed infiltrative brain tumors that discloses tumor invasion at the radiological tumor borders. This technique can be applied to evaluate the sensitivity of alternative imaging methods to detect scattered tumor cells at tumor borders. Accurate methods for detection of infiltrative tumor cells will improve the possibility of performing radical tumor resection. In future studies, the method could also be used for in vivo studies of tumor invasion.

Place, publisher, year, edition, pages
2016. Vol. 125, no 5, p. 1155-1166
Keywords [en]
diffuse low-grade glioma; magnetic resonance imaging; tumor border; tumor cell infiltration; oncology
National Category
Neurology
Identifiers
URN: urn:nbn:se:uu:diva-281052DOI: 10.3171/2015.10.JNS15583ISI: 000386106100013PubMedID: 26918468OAI: oai:DiVA.org:uu-281052DiVA, id: diva2:912639
Available from: 2016-03-17 Created: 2016-03-17 Last updated: 2018-08-08Bibliographically approved
In thesis
1. Towards new tools for clinical evaluation and visualization of tumor growth in patients with glioma
Open this publication in new window or tab >>Towards new tools for clinical evaluation and visualization of tumor growth in patients with glioma
2018 (English)Doctoral thesis, comprehensive summary (Other academic) [Artistic work]
Abstract [en]

Gliomas are derived from glial cells and are the most common type of primary brain tumors in adults. Gliomas are classified by the World Health Organization (WHO) according to their malignancy grade and histological and molecular features. Malignancy grades range from I to IV. WHO grade I tumors are benign tumors, mostly occurring in childhood. High-grade gliomas (WHO grades III and IV) are undifferentiated and fast-growing tumors, with glioblastoma being the most common and malignant form. Patients with glioblastomas have a median survival of only 15 months. Clinical outcomes vary, however, and markers are needed to assist in the decision-making process and management of these patients. PROX1 is a transcription factor critical for embryonic development, with a role in cell cycle control and progenitor cell differentiation. Apart from its role in normal central nervous system development, PROX1 has been ascribed both tumor suppressive and oncogenic roles in several human cancers. The role of PROX1 as a prognostic factor for survival in patients with glioblastomas was the focus of paper I.

Gliomas WHO grade II, also called diffuse low-grade gliomas (DLGGs), are well-differentiated tumors that occur mainly in adult life, with a peak incidence at around 30–35 years of age and a median survival of 5–10 years. DLGGs grow continuously at a rate of a few mm per year and have a strong tendency to infiltrate the white matter tracts surrounding the tumor. Eventually these tumors transform into high-grade gliomas, but, as is the case with glioblastomas, there is a large variety of clinical outcomes. For radiological diagnosis, magnetic resonance imaging (MRI) is routinely used, often in combination with advanced MRI. Positron emission tomography with amino acid tracers provides additional diagnostic accuracy. From a histological as well as imaging point of view, DLGGs are heterogeneous tumors. The heterogeneity of DLGGs, in particular the correlation between radiological and histological tumor features, was the focus of paper II & paper III.

Seizures are amongst the most common presenting symptoms of patients with gliomas. Seizure semiology in patients with brain tumors and other structural brain lesions is closely related to the anatomical location of the lesion and the involvement of functional networks. A possible dynamic interplay between the anatomical region of seizure onset and connected target areas within the network was the focus of paper IV.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 83
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1486
Keywords
PROX1, Histology, MRI, PET, Epilepsy, Co-registration
National Category
Medical and Health Sciences
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-356846 (URN)978-91-513-0410-6 (ISBN)
Public defence
2018-11-30, Aula Gunnesalen, Sjukhusvägen 1, ingång 10, Uppsala, SE, 13:00 (English)
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Available from: 2018-10-09 Created: 2018-08-08 Last updated: 2018-10-16

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Zetterling, MariaRoodakker, Kenney R.Berntsson, Shala GhaderiEdqvist, Per-Henrik DLatini, FrancescoLandtblom, Anne-MariePontén, FredrikAlafuzoff, IrinaLarsson, Elna-MarieSmits, Anja

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Zetterling, MariaRoodakker, Kenney R.Berntsson, Shala GhaderiEdqvist, Per-Henrik DLatini, FrancescoLandtblom, Anne-MariePontén, FredrikAlafuzoff, IrinaLarsson, Elna-MarieSmits, Anja
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