H3K27M-mutant diffuse midline glioma is a malignant glioma that was newly added to the World Health Organization classification in 2016. In diffuse midline glioma, the H3K27M-mutant sometimes develops sub-acutely and requires a differential diagnosis from encephalomyelitis. Here, we report a case of adult-onset diffuse midline glioma that was diagnosed by immunostaining for histone 327 after death. The present case required a differential diagnosis of autoimmune cervical myelitis and brainstem encephalitis

Arakawa, Yoshiki

Ayaki, Takashi

Ikeda, Akio

Kuzuya, Akira

Minamiguchi, Sachiko

Mitsuhashi, Masahiro

Takahashi, Ryosuke

Togawa, Natsuko

Yamashita, Hirofumi

Neurology and Clinical Neuroscience

English

Natsuko Togawa

Masahiro Mitsuhashi

Hirofumi Yamashita

Sachiko Minamiguchi

Yoshiki Arakawa

Takashi Ayaki

Akira Kuzuya

Akio Ikeda

Ryosuke Takahashi

Crossref

 immunostaining after death, which required differentiation from brainstem encephalitis and myelitis 

Kyoto University Research Information Repository

Neurol Clin Neurosci. 2023;11:239–241.   | 239wileyonlinelibrary.com/journal/ncn31  |  C A SE REPORTA 26- year- old Japanese man presented with the back of the neck pain and right arm weakness for 5 days. He had no significant past medical or family history. Cranial magnetic resonance imaging (MRI) on day 7 of onset showed hyperintensity lesions from the me-dulla oblongata to the cervical cord on T2- weighted MRI, and MRI findings on day 13 of onset showed partially enhanced images on gadolinium- enhanced T1- weighted MRI (Figure 1A– E).The patient was tentatively diagnosed with inflammatory de-myelinating disease. Despite immunotherapies with steroids, intra-venous immunoglobulin (IVIg), and plasmapheresis, the symptoms progressed rapidly at 2 months after the onset, and he needed mechanical ventilation. Therefore, he was transferred to our hospital 4 months after the onset.MRI findings showed that the hyperintensity lesion in the me-dulla oblongata had gradually expanded at 4 months from the onset. Moreover, 18F- fluorodeoxyglucose positron emission tomography (FDG- PET) showed upregulation of the signal intensity in the me-dulla oblongata lesion (Figure 1I). The patient underwent a biopsy of the medulla oblongata lesion and external decompression surgery for hydrocephalus 5 months after the onset.The medulla oblongata lesion biopsy revealed increased glial cells, perivascular lymphocyte infiltration, as well as a small num-ber of large cells observed with hematoxylin– eosin (HE) stain-ing (Figure 1J). Immunohistochemistry revealed the absence of Received: 6 January 2023  | Revised: 5 April 2023  | Accepted: 6 April 2023DOI: 10.1111/ncn3.12718  C A S E  R E P O R TA case of adult- onset diffuse midline glioma diagnosed by histone H3K27M immunostaining after death, which required differentiation from brainstem encephalitis and myelitisNatsuko Togawa1  |   Masahiro Mitsuhashi1 |   Hirofumi Yamashita2 |   Sachiko Minamiguchi3 |   Yoshiki Arakawa4 |   Takashi Ayaki1 |   Akira Kuzuya1 |   Akio Ikeda1 |   Ryosuke Takahashi1This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.© 2023 The Authors. Neurology and Clinical Neuroscience published by Japanese Society of Neurology and John Wiley & Sons Australia, Ltd.1Department of Neurology, Kyoto University Hospital, Kyoto, Japan2Department of Neurology, Japanese Red Cross Wakayama Medical Center, Wakayama, Japan3Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan4Department of Neurosurgery, Kyoto University Hospital, Kyoto, JapanCorrespondenceTakashi Ayaki, Neurology, Kyoto University Hospital room 426, 1st clinical research wing, 54 Kawaharacho, Shogoin, Sakyo- ku Kyoto, Japan.Email: ayaki520@kuhp.kyoto-u.ac.jpFunding informationMEXT KAKENHI, Grant/Award Number: 19K16277AbstractH3K27M- mutant diffuse midline glioma is a malignant glioma that was newly added to the World Health Organization classification in 2016. In diffuse midline glioma, the H3K27M- mutant sometimes develops sub- acutely and requires a differential diag-nosis from encephalomyelitis. Here, we report a case of adult- onset diffuse midline glioma that was diagnosed by immunostaining for histone H3K27M after death. The present case required a differential diagnosis of autoimmune cervical myelitis and brainstem encephalitis.K E Y W O R D Sadult onset, diffuse midline glioma, H3K27M- mutant, long cord lesion240  |    TOGAWA et al.IDH- 1R132H mutation. Ki- 67 was also positive in cells other than lymphocytes (Figure 1K); however, p53 was negative and ATRX was retained.Conversely, CD3- positive T cells were observed around the peri-vascular area in the medulla oblongata lesion (Figure 1L), and the main infiltrating cells were CD68- positive histiocytes in the biopsy F I G U R E  1  At 7 days after the onset, the T2- weighted axial image showed hyperintensity at the right medulla oblongata (A), and the sagittal image showed hyperintensity at the C1- C5 spinal cord (B). At 13 days after the onset, gadolinium- enhanced T1- weighted sagittal image showed partial enhancement at the C3- 4 spinal cord (C) and gadolinium- enhanced T1- weighted axial images at the C3- 4 spinal cord (D– E). At 6 months after the onset, the T2- weighted axial image showed heterogeneous hyperintensity and expanding lesion at the medulla oblongata (F), the sagittal image shows an enlarged spinal cord lesion and atrophied spinal cord (G), and gadolinium- enhanced T1- weighted axial image (H). Head 18F- fluorodeoxyglucose positron emission tomography shows upregulation of the signal intensity on the medulla oblongata lesion (I). Hematoxylin– eosin staining (J), immunostaining with Ki- 67 (K), CD3 (L), CD68 (M), and H3 K27M- mutant- specific antibody (N).(A) (B) (C) (D)(E) (F) (G) (H)(I) HEH3K27M(J)(N)100μm100μm100μm500μm100μm(L) (M)Ki-67CD3 CD68(K) 20494173, 2023, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/ncn3.12718 by Cochrane Japan, Wiley Online Library on [27/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License    |  241TOGAWA et al.tissue obtained from a tumor in the fourth ventricle (Figure 1M), while CD20- positive B cells were absent. Based on these pathological findings, a diagnosis of autoimmune brainstem myelitis was made.On neurological examination at 6 months after the onset, he had right abduction nerve palsy; weakness of the right facial muscle; loss of muscle contraction in the neck, trunk, and limbs; loss of deep tendon reflex; Babinski reflex on the left; sensory impairment on both sides below the neck. The routine laboratory tests revealed an abnormal cerebrospinal fluid (CSF) protein concentration of 518.9 mg/dL.Proceeding MRI scans at 6 months after onset showed that the medulla oblongata and spinal cord lesions were further enlarged (Figure 1F– H). At 7 months after onset, a urinary tract infection led to septic shock and the patient died 2 days later. No consent for au-topsy was obtained.Shortly after the patient's death, an antibody against the H3K27M- mutant, which is highly specific for H3K27M- mutant dif-fuse midline glioma (DMG), became available on a commercial basis. The biopsied sample was considered positive for the H3K27M- mutant- specific antibody (Figure 1N). Based on the immunohisto-chemistry results, we finally diagnosed the patient with DMG.2  |  DISCUSSIONThough rarely, cases of DMG in adults have been reported.1 Recently, immunostaining with the H3K27M antibody can specifi-cally and simultaneously detect multiple K27M mutations in histone H3. The H3K27M mutation is specific for DMG. A previous study reported that the K27M- mutant caused a global reduction in tri-methylation level in H3K27.2 Immunostaining with the H3K27M an-tibody can specifically and simultaneously detect K27M mutations in histone H3.The lesions usually occur in the pons in cases of pediatric pa-tients. However, in adults, the tumor site is mainly in the thalamus and less frequently in the medulla oblongata and spinal cord.1,3On imaging examinations, DMG usually demonstrates a non- uniform hyperintensity on T2- weighted images. The characteristics of gadolinium enhancement vary from ring enhancement to the ab-sence of enhancement.3In clinical situations, subacute onset with long cord lesions re-quires a differential diagnosis between DMG and inflammatory diseases.Neurologists should consider that the H3K27M antibody is not always available in clinical situations, as this antibody is not used routinely in clinicopathological examinations. Given the clinical and pathological features of DMG, neurologists should seek more de-tailed pathological consultation if they suspect the presence of DMG.ACKNOWLEDG MENTSNot applicable.CONFLIC T OF INTERE S T S TATEMENTAuthors declare no Conflict of Interest for this article.FUNDING INFORMATIONThis work was supported by the MEXT KAKENHI Grant Number 19K16277.ORCIDNatsuko Togawa  https://orcid.org/0000-0002-3063-0236 R E FE R E N C E S 1. Qiu T, Chanchotisatien A, Qin Z, et al. Imaging characteristics of adult H3 K27M- mutant gliomas. J Neurosurg. 2020;133:1662- 1670. 2. Bender S, Tang Y, Lindroth AM, et al. Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mu-tant pediatric high- grade gliomas. Cancer Cell. 2013;24:660- 672. 3. Lasocki A, Abdalla G, Chow G, Thust SC. Imaging features associ-ated with H3 K27- altered and H3 G34- mutant gliomas: a narrative systematic review. Cancer Imaging. 2022;22:63.How to cite this article: Togawa N, Mitsuhashi M, Yamashita H, et al. A case of adult- onset diffuse midline glioma diagnosed by histone H3K27M immunostaining after death, which required differentiation from brainstem encephalitis and myelitis. Neurol Clin Neurosci. 2023;11:239-241. doi:10.1111/ncn3.12718 20494173, 2023, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/ncn3.12718 by Cochrane Japan, Wiley Online Library on [27/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

A case of adult-onset diffuse midline glioma diagnosed by histone H3K27M immunostaining after death, which required differentiation from brainstem encephalitis and myelitis

https://repository.kulib.kyoto-u.ac.jp/dspace/bitstream/2433/293639/1/ncn3.12718.pdf

A case of adult-onset diffuse midline glioma diagnosed by histone H3K27M immunostaining after death, which required differentiation from brainstem encephalitis and myelitis

Abstract

Similar works

Full text

Available Versions

Crossref

Kyoto University Research Information Repository