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J Neurosurg. 2016 Nov;125(5):1155-1166. Epub 2016 Feb 26.

Extension of diffuse low-grade gliomas beyond radiological borders as shown by the coregistration of histopathological and magnetic resonance imaging data.

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Department of Neuroscience, Neurosurgery, Uppsala University.
Department of Neurosurgery, Uppsala University Hospital.
Department of Neuroscience, Neurology, Uppsala University.
Department of Neurology, Uppsala University Hospital.
Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University.
Center for Medical Image Science and Visualization, Linköpings University, Linköping, Sweden; and.
Department of Immunology, Genetics and Pathology, Uppsala University.
Department of Pathology and Cytology, Uppsala University Hospital.
Department of Surgical Sciences, Radiology, Uppsala University.
Department of Radiology, Uppsala University Hospital, Uppsala.
Danish Epilepsy Center, Dianalund, Denmark.


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.


DLGG = diffuse low-grade glioma; DTI = diffusion tensor imaging; FLAIR = fluid-attenuated inversion recovery; PACS = picture archiving and communication system; SE = spin echo; diffuse low-grade glioma; magnetic resonance imaging; oncology; tumor border; tumor cell infiltration

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