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Characterization of Diffuse Gliomas With Histone H3-G34 Mutation by MRI and Dynamic 18F-FET PET

Vettermann, Franziska J., MD*†; Felsberg, Jörg, MD; Reifenberger, Guido, MD; Hasselblatt, Martin, MD§; Forbrig, Robert, MD; Berding, Georg, MD; la Fougère, Christian, MD**; Galldiks, Norbert, MD††‡‡§§; Schittenhelm, Jens, MD∥∥; Weis, Joachim, MD¶¶; Albert, Nathalie L., MD*†; Schüller, Ulrich, MD***†††‡‡‡

doi: 10.1097/RLU.0000000000002300
Original Articles

Background Recent data suggest that diffuse gliomas carrying mutations in codon 34 of the H3 histone family 3A protein represent a very rare, distinct subgroup of IDH–wild type malignant astrocytic gliomas. However, characteristics detectable by MRI and 18F-FET PET in H3-G34-mutant gliomas are unknown.

Methods We report on MRI and 18F-FET PET findings in 8 patients from 4 German centers with H3-G34-mutant diffuse gliomas. MRI analyses included multifocality, contrast enhancement, necrosis, cysts, hemorrhages, calcification, and edema. 18F-FET PET characteristics were evaluated on the basis of static 18F-FET PET parameters, such as maximal tumor-to-background ratio (TBRmax) and biological tumor volume (BTV), as well as the minimal time-to-peak (TTPmin) obtained from dynamic 18F-FET PET data.

Results MRI showed multifocal lesions in 2 of 8, contrast enhancement in 6 of 8, necrosis in 3 of 8, cysts in 3 of 8, hemorrhage in 1 of 8, and calcifications in 1 of 8 patients. None of the tumors showed marked peritumoral edema. However, all 8 H3-G34-mutant gliomas were characterized by a high uptake intensity on 18F-FET PET with a median TBRmax of 3.4 (range, 2.5–11.7) and a relatively diffuse uptake pattern leading to a large BTV (median, 41.9 mL; range, 7.5–115.6). Dynamic PET data revealed a short median TTPmin of 12.5 minutes.

Conclusions MRI features of diffuse gliomas with H3-G34 mutation may present very heterogeneously with some cases not even fulfilling the imaging criteria of high-grade glioma. In contrast, in 18F-FET PET, these tumors show an extensive and diffuse tracer uptake resulting in large BTV with a high TBRmax and a short TTPmin, thus resembling PET characteristics of aggressive high-grade gliomas, namely, glioblastomas.

From the *Department of Nuclear Medicine, University Hospital, LMU Munich, Munich;

German Cancer Consortium (DKTK), partner site Munich;

Institute for Neuropathology, Heinrich-Heine-University, Düsseldorf, and German Cancer Consortium (DKTK), partner site Essen/Düsseldorf;

§Institute for Neuropathology, University of Münster, Münster;

Institute of Neuroradiology, University Hospital, LMU Munich, Munich;

Department of Nuclear Medicine, Hannover Medical School, Hannover;

**Department of Nuclear Medicine and Clinical Molecular Imaging, Eberhard Karls University, Tübingen;

††Department of Neurology, University of Cologne, Cologne;

‡‡Institute for Neuroscience and Medicine (INM-3), Forschungszentrum Juelich, Juelich;

§§Center for Integrated Oncology (CIO), Universities of Cologne and Bonn, Cologne;

∥∥Institute of Neuropathology, Department of Pathology and Neuropathology, University of Tübingen, and Comprehensive Cancer Center Tübingen-Stuttgart, site Tübingen;

¶¶Institute of Neuropathology, RWTH Aachen University, Aachen;

***Institute of Neuropathology, University Medical Center, Hamburg-Eppendorf;

†††Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf; and

‡‡‡Research Institute Children’s Cancer Center Hamburg, Hamburg, Germany.

Received for publication July 26, 2018; revision accepted August 21, 2018.

N.L.A. and U.S. shared last authorship.

Conflicts of interest and sources of funding: U.S. is supported by the Fördergemeinschaft Kinderkrebs-Zentrum Hamburg. None declared to all other authors.

Authorship: All authors contributed to writing the manuscript. F.J.V., N.L.A., and U.S. designed the study. All other authors contributed to imaging or histology review.

Correspondence to: Ulrich Schüller, MD, Research Institute Children's Cancer Center Hamburg Martinistrasse 52, N63 (HPI), D-20251 Hamburg, Germany. E-mail: u.schueller@uke.de.

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